Associating Liver Partition And Portal Vein Ligation For Staged Research Articles

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

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. A retrospective analysis of patients undergoing ALPPS from September 2022 to December 2023 was performed. 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. 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.

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

BackgroundIn 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.MethodsThe 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.ResultsOpen 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).ConclusionRobotic 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.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats

BackgroundThis animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). MethodsWistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. ResultsIn ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DiscussionThis study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.

Giant hepatocellular carcinoma in non-cirrhotic liver: Treatment with ALPPS and MINIALPPS

Background: Oncological resection of liver tumors continues to be the best alternative to increase survival and the disease-free period of patients. Thanks to liver regeneration, liver hypertrophy techniques are a great alternative in the surgical management of patients with high tumor burden. A few years ago, a surgical technique for liver hypertrophy called ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy) was described. In recent years, groups in Chile and Argentina have developed a variant of this which they have called MINIALPPS.

Increase of Liver Function and Volume after ALPPS Determined by MRI in a Rat Model

Introduction: It has been hypothesized that rapid increase of liver volume after ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) is not accompanied by a proportional increase of function. This study uses a rat models of major liver resection (LR), ALPPS and portal vein ligation (PVL) to test this hypothesis by measuring liver volume and function with contrast-enhanced magnetic resonance imaging (MRI). Methods: Wistar rats (200-250g) were randomly allocated to LR, ALPPS or PVL. T1-weighted MRI scans (7.0T MR Solutions,Guildford,UK) were performed until postoperative day 5. Uptake kinetics (2D-FLASH;TR/TE=589/8) of Primovist® (1mmol/kg,Bayer AG,Berlin, Germany) were measured in the future liver remnant (FLR) and spleen (blood pool). Liver volume was assessed during the excretion phase (2D-FLASH;TR/TE=4150/11; thickness 1mm). Liver function of the FLR was defined as the inverse value of time [min] from injection of Primovist® to maximum signal intensity multiplied by respective volume of the FLR [ccm]. Results: Percent increase of FLR volume overestimates FLR function at day 1 in all three, ALPPS, LR and PVL. From day 2, function and volume of the FLR increase proportionally in all procedures (Figure 1). Percent increase of liver function exceeds liver volume from day 2 until day 5 in ALPPS and LR, but not in PVL. Conclusion: This animal study rejects the hypothesis that functional increase is not proportional to volume increase in ALPPS. While function is impaired on day 1, ALPPS leads to a congruent increase of volume and function after day 1, similar to LR.

Role of CT in Two-Stage Liver Surgery.

Complete resection is the only potentially curative treatment for primary or metastatic liver tumors. Improvements in surgical techniques such as conventional two-stage hepatectomy (TSH) with portal vein embolization and ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) promote hypertrophy of the future liver remnant (FLR), expanding resection criteria to include patients with widespread hepatic disease who were formerly not considered candidates for resection. Radiologists are essential in the multidisciplinary approach required for TSH. In particular, multidetector CT has a critical role throughout the various stages of this surgical process. The aims of CT before the first stage of TSH are to define the feasibility of surgery, assess the number and location of liver tumors in relation to relevant anatomy, and provide a detailed anatomic evaluation, including vascular and biliary variants. Volume calculation with CT is also essential to determine if the FLR is sufficient to avoid posthepatectomy liver failure. The objectives of CT between the first and second stages of TSH are to recalculate liver volumes (ie, assess FLR hypertrophy) and depict expected liver changes and complications that could modify the surgical plan or preclude the second stage of definitive resection. In this review, the importance of CT throughout different stages of TSH is discussed and key observations that contribute to surgical planning are highlighted. In addition, the advantages and limitations of MRI for detection of liver metastases and assessment of complications are briefly described. ©RSNA, 2022.

ALPPS Procedure. The New Frontier in Advanced Liver Surgery. Single Centre Experience and Literature Review

Introduction: Presentation of the first experience of a liver surgery center in applying an innovative procedure - ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) for massive liver tumors. This medod has been performed in the surgery clinic 2 since 2018 in patients with massive primary or metastatic liver tumors, whose future residual liver volume is considered too small to perform curative liver resection safely. Until recently, these conditions assigned large tumors occupying more than 75-90% of the liver to the group of unresectable tumors. Prospectively, the ALPPS procedure was evaluated to convert unresectable liver tumors due to the small residual liver volume into resectable ones. Literature data were systematically reviewed using PubMed, Scopus, Google Scholar. Materials and methods: Since June 2018, 18 ALPPS procedures were performed in patients aged 62 +-8 years. Indications for surgical resection were liver metastases of colorectal cancer in 7 cases, perihilar cholangiocarcinoma in 4 cases, hepatocellular carcinoma in 6 cases, and GIST metastases 1 case. From the literature data we analyzed articles from 2014 to 2019. Results: Residual liver volume was calculated on CT angiography using the program included in the Siemens machine software and was 252 +- 115 ml (19.4 +- 6.2%) before ALPPS-1 and 542 +- 165 ml (30.7 +- 6.5%) before ALLPS-2 (P 0.001). The increase in residual liver volume between the two procedures was 60.4 +- 38% (range: 31-110%, P 0.001). The mean time between the first and second procedure was 9.4 +- 2.3 days. Average hospital stay was 28.4 +- 9.2 days. Postoperative morbidity 34.8%, mortality 0. Survival at 18 months was 100%. Conclusion: The ALPPS technique allows us to increase the resectability rate in patients with initially unresectable liver tumors with favorable postoperative outcomes. Careful selection of patients for a major complex procedure such as ALPPS allowed us to avoid postoperative mortality. Liver cirrhosis, cholestasis, and intraoperative hemorrhage are major factors for the development of postoperative morbidity.

Editorial.

Liver surgery continues to evolve, as knowledge of liver anatomy and physiology deepens, new technologies are introduced, and the experience of surgical teams increases. Internationally, liver surgery is part of a very well-defined subspecialty today, namely "hepato-biliary-pancreatic surgery". The United States has a two-year post-residency training system (Fellowship). Europe has an examination organized by UEMS in which candidates must demonstrate specific training in one or more HPB units. A two-year training certificate in hepato-biliary-pancreatic surgery was introduced in Romania, coordinated by three centers: Fundeni Clinical Institute in Bucharest, Sfantul Spiridon Hospital in Iasi and Regional Institute of Gastroenterology and Hepatology in Cluj-Napoca. The first two centers also provide training for liver transplantation. This special issue primarily reflects the experience of these three centers, to which are added newer ones, under development. One of these new centers (the Surgical Department II "Sf. Maria" Hospital in Bucharest), represented by C. Stroescu et al, presents a valuable experience in HPB surgery accumulated in the last 7 years. The importance of anatomy in liver surgery is underlined by the work of L. Simion et al, which analyzes the anatomical variants of the hepatic artery and their importance in resection and transplant surgery. Current liver surgery necessarily involves intraoperative ultrasound, which is highlighted in the excellent review by A. Bartos et al in the particular case of resections for hepatocellular carcinoma. Also, the importance of this exploration results from the experience of liver resections for metastases of stromal gastrointestinal tumors (GIST) analyzed by A. Kraft et al. An important advance in liver surgery was the minimally invasive, laparoscopic or robotic approach. M. Marino et al. present an interesting experience in robotic liver surgery. Among the other topics addressed, we retain the method called ALPPS (Associating liver partition and portal vein ligation for staged hepatectomy). Viewed with reservations at first and even met with severe criticism, ALPPS seems to have prevailed now, the results being considered convincing by most authors. This is reflected in two articles: A review article by F. Botea et al based also on an important experience both in Fundeni Hospital, but mainly in the Department of Surgery in Zurich and Kiel. The personal experience of A. Hotineanu et al. We were honored to include this article from the Republic of Moldova, especially since there is still a close connection between the surgery center at the Republican Hospital in Chisinau and the Romanian surgery. The progress made in liver transplantation is reflected in the work of Nicolaescu et al on the experience of Fundeni center in hypothermic mechanical oxygenated perfusion of liver grafts, one of the most important developments in transplantation in recent years, which contributed significantly to the continuous improvement of postoperative results. Hydatid cyst surgery could not be missed, in a country where this pathology is still widespread enough. The work of C. Molnar et al addresses a complicated form of the disease, namely multiple hydatid cyst. This special issue covers also the topic of interventional treatment, in the article of Lupascu et al about the percutaneous drainage of liver abscess. Two of the works are dedicated to bile duct surgery: A. Bartos at al. presents the personal experience on portojejunostomy in cases of complex lesions of the extrahepatic bile duct; R. Popescu et al. presents the personal experience on the management of residual gallbladder and cystic duct stump stone after cholecystectomy. The video presentations bring a special added value in a difficult and spectacular surgery, not without risks. It is worth noting first of all the video with the resection of a giant hepatic artery aneurysm (V. Brasoveanu et al), as well as the two films of complex ultrasound- guided resections of F. Botea et al. I am convinced that the video of M. Marino et al on robotic left hemihepatectomy will surely be very much appreciated by the readers of Chirurgia.

ALPPS and minialpps. Alternatives between liver hypertrophy techniques. Presentation of two cases in liver disease of non-colorectal origin

Presenter: Fabio Vergara MD | IPS Universidad de Antioquia, Clinica Leon XIII Background: Liver resections are the treatment of choice for most liver tumors. Thanks to liver regeneration, various procedures have appeared to stimulate liver hypertrophy in cases where it is required. Among them is the ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy), which consists of performing a hepatectomy in two stages, achieving faster hypertrophy and in less time. This surgical technique can have high morbidity and mortality rates, so it is very important to properly select patients. In recent years, groups from Chile and Argentina have developed a variant in this technique which they have called Mini-ALPPS, where the hepatic transection is minor, thus reducing the morbidity that this part of the surgery can bring. Methods: We present two cases of ALPPS and Mini-AlPPS in liver disease of non colorectal origin. The first case of a two-stage hepatectomy using ALPPS is a 65-year-old male patient, with MRI of the abdomen shows a giant liver in the right lobe and part of segment IV compatible with probable hepatocarcinoma over non-cirrhotic liver. Hepatic volumetry show insufficient hepatic remnant, it was decided to perform an ALPPS with the aim of obtaining a faster hepatic hypertrophy. The first time was performed by laparoscopic technique, achieving right portal ligation and hepatic transection. At 10 days, a new abdominal tomography was performed to assess hypertrophy. Then proceed to the second time of the ALPPS, with an open approach. Hepatic transection is completed with right hepatic artery ligation, right bile duct control and right hepatic vein section. In the second case we used de Mini-ALLPS strategy. A 52-year-old woman with a history of resected retroperitoneal sarcoma. In the follow-up hepatic recurrence of sarcoma. MRI confirms presence of hepatic bilobar disease in the right lobe and segment IV with a single lesion in the left lateral section. It was decided to perform MiniALPPS with resection of the metastasis of the left lateral section, right portal ligation and hepatic section of 3cms deep in the firs stage. At 10 postoperative days a CT scan of the abdomen shows compensatory hypertrophy of the left lateral section. In the second stage an extended right hepatectomy was performed. Results: In the two cases the procedure was uncomplicated, did not require blood transfusion or vasopressor support, extubation and transfer to the ICU was achieved for surveillance. The ALPPS case had no signs of liver failure, he was discharged after 8 days. The pathology shows a hepatocarcinoma on non-cirrhotic liver. The MiniALPPS case has present type B postoperative liver failure, it required vasopressor support and blood transfusion. The pathology confirmed sarcoma metastases Conclusion: ALPPS and MiniALPPS are an alternative in the treatment of liver tumors where the liver remnant is insufficient. They can use when the cause of its tumor biology and we need a hypertrophy is less time or when the other ways of generating hypertrophy are failed. However, it is a procedure that can have high morbidity and mortality, so it is important to select patients in a multidisciplinary team.

Exploration of the Transcriptional Landscape of ALPPS Reveals the Pathways of Accelerated Liver Regeneration.

Background and Aims: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy), a novel 2-staged hepatectomy, dramatically accelerates liver regeneration and thus enables extensive liver tumor resection. The signaling networks underlying the ALPPS-induced accelerated regeneration process are largely unknown.Methods: We performed transcriptome profiling (TP) of liver tissue obtained from a mouse model of ALPPS, standard hepatectomy (68% model), and additional control surgeries (sham, PVL and Tx). We also performed TP using human liver biopsies (n = 5) taken from the occluded lobe and the future liver remnant (FLR) during the first step of ALPPS surgery (4–5 h apart). We used Oncofinder computational tools, which covers 378 ISPs, for unsupervised, unbiased quantification of ISP activity.Results: Gene expression cluster analysis revealed an ALPPS specific signature: the IGF1R Signaling Pathway (Cell survival), the ILK Pathway (Induced cell proliferation), and the IL-10 Pathway (Stability determination) were significantly enriched, whereas the activity of the Interferon Pathway (Transcription) was reduced (p < 0.05). Further, the PAK- and ILK-associated ISPs were activated at an earlier time point, reflecting significant acceleration of liver regeneration (p < 0.001). These pathways, which were also recovered in human liver biopsies, control cell growth and proliferation, inflammatory response, and hypoxia-related processes.Conclusions: ALPPS is not a straightforward addition of portal vein ligation (PVL) plus transection—it is more. The early stages of normal and accelerated liver regeneration are clearly discernible by a significantly increased and earlier activation of a small number of signaling pathways. Compounds mimicking these responses may help to improve the ALPPS method and further reduce the hospitalization time of the patient.

Defining Benchmark Outcomes for ALPPS.

The aim of this study was to use the concept of benchmarking to establish robust and standardized outcome references after the procedure ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy). The recently developed ALPPS procedure, aiming at removing primarily unresectable liver tumors, has been criticized for safety issues with high variations in the reported morbidity/mortality rates depending on patient, disease, technical characteristics, and center experience. No reference values for relevant outcome parameters are available. Among 1036 patients registered in the international ALPPS registry, 120 (12%) were benchmark cases fulfilling 4 criteria: patients ≤67 years of age, with colorectal metastases, without simultaneous abdominal procedures, and centers having performed ≥30 cases. Benchmark values, defined as the 75th percentile of the median outcome parameters of the centers, were established for 10 clinically relevant domains. The benchmark values were completion of stage 2: ≥96%, postoperative liver failure (ISGLS-criteria) after stage 2: ≤5%, ICU stay after ALPPS stages 1 and 2: ≤1 and ≤2 days, respectively, interstage interval: ≤16 days, hospital stay after ALPPS stage 2: ≤10 days, rates of overall morbidity in combining both stage 1 and 2: ≤65% and for major complications (grade ≥3a): ≤38%, 90-day comprehensive complication index was ≤22, the 30-, 90-day, and 6-month mortality was ≤4%, ≤5%, and 6%, respectively, the overall 1-year, recurrence-free, liver-tumor-free, and extrahepatic disease-free survival was ≥86%, ≥50%, ≥57%, and ≥65%, respectively. This benchmark analysis sets key reference values for ALPPS, indicating similar outcome as other types of major hepatectomies. Benchmark cutoffs offer valid tools not only for comparisons with other procedures, but also to assess higher risk groups of patients or different indications than colorectal metastases.

Left- versus right-sided hepatectomy with hilar en-bloc resection in perihilar cholangiocarcinoma

BackgroundMajor liver resections with portal vein resection (PVR) have emerged as the preferred treatment for patients with perihilar cholangiocarcinoma (pCCA). Whether the resection of the liver should be preferably performed as left- (LH) or right-sided hepatectomy (RH) with or without hilar en-bloc technique is still subject of ongoing debate. MethodsBetween 2011 and 2016, 91 patients with pCCA underwent surgery in curative intent at our institution. Perioperative, pathological and survival data from all consecutive patients undergoing hilar en-bloc resection for pCCA were analyzed retrospectively. Patients undergoing hepatoduodenectomy (n = 8) or ALPPS (Associating liver partition and portal vein ligation for staged hepatectomy) (n = 2) were excluded from the analysis. ResultsTumor grading, microvascular invasion, lymphovascular invasion, N-category, T-category, R-status and UICC-tumor staging were similar in the RH (n = 45) and LH (n = 36) groups. Perioperative morbidity and mortality were higher after RH compared to LH (mortality: 15.6% (7/45) vs. 8.3% (3/36) p = 0.003). Three-year (62% vs. 51%) and the 5-year OS (30% vs. 46%) were comparable between LH and RH groups respectively (p = 0.519, log rank). ConclusionsThe present study supports the concept of surgically aggressive therapy in pCCA. LH and RH hilar en-bloc resection demonstrate a comparable long-term survival, suggesting that LH hilar en-bloc resections are feasible and safe in high-volume centers.

How to increase the resectability of initially unresectable colorectal liver metastases: A surgical perspective.

Although surgical resection is the only treatment of choice that can offer prolonged survival and a chance of cure in patients with colorectal liver metastases (CRLM), nearly 80% of patients are deemed to be unresectable at the time of diagnosis. Considerable efforts have been made to overcome this initial unresectability, including expanding the indication of surgery, the advent of conversion chemotherapy, and development and modification of specific surgical techniques, regulated under multidisciplinary approaches. In terms of specific surgical techniques, portal vein ligation/embolization can increase the volume of future liver remnant and thereby reduce the risk of hepatic insufficiency and death after major hepatectomy. For multiple bilobar CRLM that were traditionally considered unresectable even with preoperative chemotherapy and portal vein embolization, two‐stage hepatectomy was introduced and has been adopted worldwide with acceptable short‐ and long‐term outcomes. Recently, ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) was reported as a novel variant of two‐stage hepatectomy. Although issues regarding safety remain unresolved, rapid future liver remnant hypertrophy and subsequent shorter intervals between the two stages lead to a higher feasibility rate, reaching 98%. In addition, adding radiofrequency ablation and vascular resection and reconstruction techniques can allow expansion of the pool of patients with CRLM who are candidates for liver resection and thus a cure. In this review, we discuss specific techniques that may expand the criteria for resectability in patients with initially unresectable CRLM.

Transition from open to laparoscopic ALPPS: The initial experience

Background: Laparoscopic ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) has only been reported in individual reports, but laparoscopic ALPPS has been the authors’ default option since 2015. Methods: A retrospective analysis of all consecutive patients undergoing ALPPS at a single referral center was performed using a prospective database from July 2011 to June 2016. Feasibility was studied by assessing conversions. The 90-day mortality and complications were analyzed using Dindo-Clavien score and the comprehensive complication index. Operative time, blood loss, volumetric growth, and hospital stay were examined. The CUSUM statistic was measured. Results: There was no mortality and no complication Dindo-Clavien grade ≥3A observed in laparoscopic ALPPS. In open ALPPS, one patient died after the procedure and 10 out of 20 patients (median CCI=21) experienced complications grade ≥3A (p=0.006). No liver failure was observed after laparoscopic ALPPS, and two patients in the open ALPPS developed complications that precluded the second stage. The hospital stay was shorter in the laparoscopic ALPPS group (11 vs 14 days; p=0.011) Conclusion: Laparoscopic ALPPS is feasible as the default procedure for patients with very small FLR, and it is not inferior to the open approach. The use of laparoscopy in ALPPS should be encouraged to surgeons experienced with complex laparoscopic HPB surgeries.

Critical Analysis of ALPPS Procedure: A Single Centre Experience

The ALPPS (Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy) method was presented to the expert public with the intention of providing a chance to patients with metastatic or primary liver cancer and a lack of residual parenchyma excluding resection therapy which is considered to be the only curative treatment. This method has been regarded as controversial due to its high mortality and morbidity on the one hand and high resection success rate on the second hand. The article presents the initial experience from one workplace. Materials and Methods: From August 2013 to June 2014 eight patients were selected for ALPPS method of hepatic resection at the Surgery of the University Hospital Ostrava Czech republic. For all patients the initial FLR (future liver remnant) volume was less than 25% and they have exhausted other treatment options for the disease. Results: The group consisted of two men and six women, aged 40 to 70. Four patients had CRC (colorectal cancer) liver metastases and two patients were diagnosed with gallbladder cancer metastatic to the liver. The first female patient suffered from hilar cholangiocarcinoma and the last female patient had leiomyosarcoma. Altogether six patients were subject to both phases of the therapy (75% of cases). From the entire patient group one female patient died after the first phase due to haemorrhagic shock, and one was assessed by the multidisciplinary team as unsustainable for the second phase. Remaining all six patients who underwent both phases of surgery had R0 resection but three of them had severe liver failure and they ended fatally. Conclusion: ALPPS is a new method for inducing rapid hypertrophy of the liver parenchyma based on the ligation the portal vein branch and in-situ splitting. However this therapy is still burdened by a relatively high rate of morbidity and mortality which are directly related to the tumour’s histological character to the age of the patient and to the functional state of their hepatic parenchyma

ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) does not affect proliferation, apoptosis, or angiogenesis as compared to standard liver resection for colorectal liver metastases

BackgroundALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a novel two-stage strategy to induce rapid hypertrophy of the future liver remnant (FLR) when patients are in danger of postoperative liver failure due to insufficient FLR. However, the effects of ALPPS on colorectal liver metastases (CRLM) are not clear so far. The aim of our study was to determine whether ALPPS induces proliferation, apoptosis, or vascularization compared to standard (one-stage) liver resection.MethodsSix patients who underwent ALPPS were matched with 12 patients undergoing standard liver resection regarding characteristics of the metastases (size, number), time of appearance (syn-/metachronous), preoperative chemotherapy, primary tumor (localization, TNM stage, grading), and patient variables (gender, age). The largest resected metastasis was used for the analyses. Tissue was stained for tumor cell proliferation (Ki67), apoptosis (TUNEL, caspase-3), vascularization (CD31), and pericytes (αSMA).ResultsVascularization (CD31; p = 0.149), proliferation (Mib-1; p = 0.244), and αSMA expression (p = 0.205) did not significantly differ between the two groups, although a trend towards less proliferation and αSMA expression was observed in patients undergoing ALPPS. Concerning apoptosis, caspase-3 staining showed significantly fewer apoptotic cells upon ALPPS (p < 0.0001), but this was not confirmed by TUNEL staining (p = 0.7344).ConclusionsALPPS does not induce proliferation, apoptosis, or vascularization of CRLM when compared to standard liver resection.

Acute Kidney Injury after ALPPS Procedure (Case Report)

Acute kidney injury (AKI) is a serious complication after major liver resection. It may be caused by post-hepatectomy liver failure (PLF). ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) procedure is an effective way for PLF prevention in cases of small future remnant volume or bilobar liver lesions, but the risk of AKI following this procedure is unknown. Herein we present and discuss the case of a 23-year-old man with hepatic alveococcosis who underwent ALPPS procedure. Despite absence of any risk factors AKI (RIFLE-F) followed by renal replacement therapy (RRT) has occurred within few hours after the first surgical stage. Only the combination of albumin and terlipressin resulted function improvement and RRT with drawal after three weeks of AKI onset. Renal dysfunction didn’t affect the liver regeneration and the second stage of ALPPS has been performed in six days after the first one. There were no signs of serious liver synthetic function deterioration, coagulopathy, jaundice or encephalo pathy. The mechanisms of AKI progression as well as the portal and systemic circulatorychanges after the first stage of ALPPS seem to be similar with hepatorenal syndrome type I. Intra- and postoperative maintenance of physiologic hemodynamics may be the key point for AKI prevention. Norepinephrine and/or terlipressin could be considered as the drugs of choice.

Transition from open to laparoscopic ALPPS for patients with very small FLR: the initial experience

BackgroundLaparoscopic ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) has previously been reported but has been the authors' default option since 2015 in patients with small future liver remnant. MethodsA retrospective analysis of all consecutive patients undergoing ALPPS at a single referral center was performed using a prospective database from July 2011 to June 2016. Feasibility was studied by assessing conversions. The 90-day mortality and complications were analyzed using a Dindo–Clavien score and the comprehensive complication index. Operative time, blood loss, volumetric growth, and hospital stay were examined. The CUSUM analysis was performed. ResultsALPPS was performed in 30 patients, 10 of whom underwent a laparoscopic approach. There was no mortality and no complication grade ≥3A observed in laparoscopic ALPPS. In open ALPPS, 10 of 20 patients experienced complications grade ≥3A (p = 0.006) and one patient died. Liver failure was not observed after laparoscopic ALPPS, but two patients in the open ALPPS group developed complications that precluded the second stage. The total hospital stay was shorter in the laparoscopic ALPPS group. ConclusionLaparoscopic ALPPS is feasible as the default procedure for patients with very small FLR, and it is not inferior to the open approach. Surgeons experienced with complex laparoscopy should be encouraged to use a laparoscopic approach to ALPPS.

The ALPPS Risk Score: Avoiding Futile Use of ALPPS.

To create a prediction model identifying futile outcome in ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) before stage 1 and stage 2 surgery. ALPPS is a 2-stage hepatectomy, which incorporates parenchymal transection at stage 1 enabling resection of extensive liver tumors. One of the major criticisms of ALPPS is the associated high mortality rate up to 20%. Using the International ALPPS Registry, a risk analysis for futile outcome (defined as 90-day or in-hospital mortality) was performed. Futility was modeled using multivariate regression analysis and a futility risk score formula was computed on the basis of the relative size of logistic model regression coefficients. Among 528 ALPPS patients from 38 centers, a futile outcome was observed in 47 patients (9%). The pre-stage 1 model included age 67 years or older [odds ratio (OR) = 5.7], and tumor entity (OR = 3.8 for biliary tumors) as independent predictors of futility from multivariate analysis. For the pre-stage 1 model scores of 0, 1, 2, 3, 4 and 5 were associated with futile risk of 2.7%, 4.9%, 8.6%, 15%, 24%, and 37%. The pre-stage 2 model included major complications (grade ≥ 3b) after stage 1 (OR = 3.4), serum bilirubin (OR = 4.4), serum creatinine (OR = 5.4), and cumulative pre-stage 1 risk score (OR = 1.9). The model predicted futility risk of 5%, 10%, 20%, and 50% for patients with scores of 3.9, 4.7, 5.5, and 6.9, respectively. Both models have an excellent prediction to assess the individual risk of futile outcome after ALPPS surgery and can be used to avoid futile use of ALPPS.

Liver kinetic growth rate predicts postoperative liver failure after ALPPS

BackgroundPosthepatectomy liver failure (PHLF) may occur after ALPPS (Associating liver partition and portal vein ligation for staged hepatectomy) despite a sufficient standardized future liver remnant (sFLR) volume. The aim of this study was to test kinetic growth rate (KGR) after ALPPS stage 1, describing the percentage increase of sFLR per day, as a predictor of PHLF after completion of ALPPS. MethodsThe ability of KGR to predict PHLF after ALPPS stage 2 was investigated in 38 patients. PHLF was defined according to the “50–50” and ISGLS criteria. ResultsCompletion of ALPPS was achieved in 95% (36/38) of patients. The incidence of PHLF was 22% (8/36) and 36% (13/36) according to “50–50” and ISGLS criteria, respectively. Whereas a sFLR cut off at 30% alone failed to predict PHLF, KGR ≥6%/day after stage 1 was associated with a significant reduced risk of PHLF (“50–50”, p = 0.03/ISGLS, p = 0.03) after stage 2. Adherence to both concomitant KGR ≥6%/day and sFLR ≥30% reduced the incidence of PHLF to 0%. ConclusionsAssessment of KGR is a novel tool to estimate the risk of PHLF after ALPPS. Respecting KGR and sFLR after ALPPS stage 1 may increase safety in patients undergoing ALPPS.