Small Future Liver Remnant Research Articles

Uncommon indications for associating liver partition and portal vein ligation for staged hepatectomy: a systematic review.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) represents an innovative surgical technique used for the treatment of large hepatic lesions at high risk for post-resection liver failure due to a small future liver remnant. The most significant amount of literature concerns the use of ALPPS for the treatment of hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and colorectal liver metastases (CRLM). On the opposite, few is known about the role of ALPPS for the treatment of uncommon liver pathologies. The objective of the present study was to evaluate the current literature on this topic. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible articles published up to February 2020 were included using the MEDLINE, Scopus, and Cochrane databases. Among the 486 articles screened, 45 papers met the inclusion criteria, with 136 described cases of ALPPS for rare indications. These 136 cases were reported in 18 different countries. Only in two countries, namely Germany and Brazil, more than ten cases were observed. As for the ALPPS indications, we reported 41 (30.1%) cases of neuroendocrine tumor (NET) metastases, followed by 27 (19.9%) cases of gallbladder cancer (GBC), nine (6.6%) pediatric cases, six (4.4%) gastrointestinal stromal tumors, six (4.4%) adult cases of benign primary liver disease, four (2.9%) adult cases of malignant primary liver disease, and 43 (31.6%) adult cases of malignant secondary liver disease. According to the International ALPPS Registry data, less than 10% of the ALPPS procedures have been performed for the treatment of uncommon liver pathologies. NET and GBC are the unique pathologies with acceptable numerosity. ALPPS for NET appears to be a safe procedure, with satisfactory long-term results. On the opposite, the results observed for the treatment of GBC are poor. However, these data should be considered with caution. The rationale for treating benign pathologies with ALPPS appears to be weak. No definitive response should be given for all the other pathologies. Multicenter studies are needed with the intent to clarify the potentially beneficial effect of ALPPS for their treatment.

Outcomes of percutaneous radiofrequency-assisted liver partition and portal vein embolization for staged hepatectomy in patients with intrahepatic cholangiocarcinoma

Purpose: Surgical resection in intrahepatic cholangiocarcinoma (ICC) is the only feasible modality with a curative ability. The challenge balances between growing the future liver remnant (FLR) in a short time and the same time preventing tumor progression and surgical complications. Assotiated liver partition and portal vein embolization for stage hepatectomy (ALPPS) gives a chance for fast kinetic growth, but with high morbidity and mortality level. Methods: This observation includes 8 comparative patients with ICC: 4 underwent PVE and 4 - ALPPS (3 - PRALPPS). PVE group has median age 62,2 years, median FLR volume was 564,4 ml, 33%. ALPPS group has median age 58,6 years, median FLR volume was 542,6 ml, 34,9%. 1 patient had classic ALPPS and 3 had miniinvasive variant of ALPPS - percutaneous radiofrequency-assisted liver partition and portal vein embolization for staged hepatectomy (PRALPPS). Results: The first stage was uncomplicated in the both groups. The median FLR volume became 785 ml (46%) in a 27,5 days and 753,9 ml (38%) in a 17,7 days in PVE and ALPPS groups respectively. Nevertheless, degree of hypertrophy was similar: 41% in PVE and 40,4% in ALPPS. Kinetic growth rate was significantly different: 1,38 and 2,62%/day respectively. Seven patients completed the second stage. Sever morbidity was revealed with only ALPPS group: grade IIIa (n-1) and grade V (n-1) according to Clavien-Dindo. The in-hospital death was associated with classical ALPPS in one patient with extremely small FLR (<30%). Conclusions: The modified ALPPS (PRALPPS) may be considered as a safe tool to achieve rapid and sufficient hypertrophy in patients with ICC.

Simultaneous ipsilateral dual (DSM-TACE and PVE) embolization (SIDE Technique) for preoperative augmentation of future liver remnant (FLR)

Purpose: Portal Vein Embolization(PVE) is a gold standard strategy to increase FLR at level of Kinetic Growth Rate (KGR) about 2.3 cc/day and to prevent posthepatectomy liver failure (PHLF). Up to 30% of patient with liver malignance still couldn't underwent surgery after PVE due to tumor progression and/or insufficient FLR regeneration during waiting period. Currently there are no methods that resolves both mentioned issues. Our aim was to develop new method that potentially will increase number of the patients with insufficient FLR that will succeed to underwent liver surgery. Results also were compared with currently developed methods of FLR augmentation such as extended liver venous deprivation (eLVD) and ALPPS. Method: 9 initially unresectable, due to small FLR, patients with colorectal liver metastases (CRLM) having more than three criteria of Fong Clinical Risk Score for CRLM, in close proximity to FLR critical structures ), were approved by Ethical Committee for Simultaneous PVE and Transarterial Chemoembolization with Degradable Starch Microspheres (DSM-TACE). Simultaneously, immediately after standard PVE, was performed oxaliplatin based DSM-TACE with short-term embolic material of the whole tumor bearing liver to be resected that safely allowed to achieve I) postembolic infarction II) pharmacologically induced hepatic Veno-Occlusive Disease(VOD(Fig 2d)) in liver to be removed, as a trigger of increased FLR regeneration(Fig.1), without biliary tree damage(Fig. 2 a,c) and what distinguishes it advantageously III) local tumor control. Results: Unprecedented FLR regeneration with KGR 23.5 cc/day(range from 17.6 to 57.25 cc/day) was observed. The latter allow us to achieve safe FLR volume to perform extended hepatectomies within recommended 2-3 weeks period to avoid chemotherapy related neutropenic window in all 9 patients even so there were no myelosuppression observed. This allows us safely shortening time to resection to 15 days in 5 last consecutive patients. In all CRLM about 60% (range from 40% to 90%) necrosis was achieved(Fig. 2 a). All patients have successfully underwent major liver resection with 0% dropout. There was no severe morbidity and mortality. Conclusion: We propose safe method of preoperative FLR adaptation which is not only second to none in the achieving liver regeneration rate but also is the only one that allows local tumor control and/or downsize borderline resectable tumors.

Preoperative future liver remnant(FLR) augmentation with local tumor control and in-situ immunization for patients with advanced hepatocellular carcinoma (HCC)

Purpose: Portal vein embolization(PVE) provokes tumor progression. Liver Cirrhosis(LC) decreases FLR regeneration capacity doubling the risk for patient dropout. Our aim was to turn weakness into a strength- develop method of FLR augmentation that converts aggressive tumor into a safe vaccine and prolonged waiting period for FLR regeneration into effective In situ immunization period Method: 3 initially unresectable patients due to small FLR with advanced hepatocellular carcinoma(HCC) and liver cirrhosis were treated. Selective transarterial chemoembolization with short term biodegradable starch microspheres(DSM-TACE), into tumor bearing liver to be resected, was followed by simultaneous PVE of latter. Upon completion of PVE selective intratumoral immunotherapy(HIT-IT) with antiPD-L1(atezolizumab 1200mg) into restored after DSM-TACE tumor arterial feeders (for selective connection with PD-L1 ligands located on tumor cells but not on normal human tissues) was done. DSM-TACE and HIT-IT was repeated one more time in all patients after postzenith decrease of T-cytotoxic cells level in peripheral blood had started. Anticancer immune response was investigated by comparison of initial histopathology specimen with specimens obtained just before second DSM-TACE+ HIT-IT and finally with specimen of resected tumor bearing liver. Latter were analyzed along with peripheral blood flow cytometry. Results: Predominantly T and NK cells response was observed. All patients had successfully underwent extended liver resection upon sufficient FLR regeneration. In all 3 cases we had achieved effective local tumor control via total or subtotal HCC necrosis, even more, in 1(33%) case planned amount of liver resection was decreased due to achieved tumor downsizing. There were no severe morbidity or Immune-related adverse events (irAEs). Conclusion: Herein we had proposed new aggressive but safe method of FLR augmentation for patients with HCC and liver cirrhosis that could potentially preclude drop out of patients during anticipated prolonged waiting period of FLR augmentation and possible improves long-term outcomes by means of tumor downsizing and HCC immunoscore conversion.

Impact of acute kidney injury after extended liver resections

BackgroundComplex liver resection is a risk factor for the development of AKI, which is associated with increased morbidity and mortality. Aim of this study was to assess risk factors for acute kidney injury (AKI) and its impact on outcome for patients undergoing complex liver surgery. MethodsAKI was defined according to the KDIGO criteria. Primary endpoint was the occurrence of AKI after liver resection. Secondary endpoints were complications and mortality. ResultsOverall, 146 patients undergoing extended liver resection were included in the study. The incidence of AKI was 21%. The incidence of chronic kidney disease (CKD) and hepatocellular carcinoma were significantly higher in patients with AKI. In the AKI group, the proportion of extended right hepatectomies was the highest (53%), followed by ALPPS (43%). Increased intraoperative blood loss, increased postoperative complications and perioperative mortality was associated with AKI. Besides age and CKD, ALPPS was an independent risk factor for postoperative AKI. A small future liver remnant seemed to increase the risk of AKI in patients undergoing ALPPS. ConclusionFollowing extended liver resection, AKI is associated with an increased morbidity and mortality. ALPPS is a major independent risk factor for the development of AKI and a sufficient future liver remnant could avoid postoperative AKI.

Extended liver resection including hypertrophy concept with portal venous embolisation for giant haemangioma. Too much surgery?

Haemangiomas of the liver are benign tumours, which are often diagnosed randomly. With an increase in size haemangiomas could become symptomatic. In this case therapeutic options, surgical or interventional, have to be weighted to a conservative approach. We present a case of a 36-year old woman with a symptomatic giant haemangioma of the right liver lobe. Because of the size of the tumor and the small future liver remnant we decided to perform a major liver resection after hypertrophy induction with a preoperative portal vein embolization; an option mainly used for major hepatectomies in malignant tumors of the liver. But however, this case shows, that using a hypertrophy concept also for benign liver tumours is the safer approach, if an extended resection is necessary and the future liver remnant is critical.

Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Registry: What Have We Learned?

In 2007, the first associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure was performed in Regensburg, Germany. ALPPS is a variation of two-stage hepatectomy to induce rapid liver hypertrophy allowing the removal of large tumors otherwise considered irresectable due to a too small future liver remnant. In 2012, the international ALPPS registry was created, and it now contains more than 1,000 cases. During the past years, improved patient selection and refinements in operative techniques, in particular, less invasive approaches such as Partial ALPPS, Tourniquet ALPPS, Ablation-assisted ALPPS, Hybrid ALPPS or Laparoscopic or Robotic approaches, have resulted in significant improvements in safety. The most frequent indication for ALPPS is colorectal liver metastases. In the first randomized controlled study, ALPPS provided a higher resectability rate than conventional two-stage hepatectomy, with similar complication rates. Long-term outcome data are still missing. The initial results of ALPPS for hepatocellular carcinoma and for perihilar cholangiocarcinoma were devastating, but with progress in surgical technic and better patient selection, ALPPS could serve as a treatment alternative in carefully selected cases, even for these tumors. ALPPS has enlarged the armamentarium of hepato-pancreato-biliary surgeons, but there is still discussion regarding how to use this novel technique, which may allow resection of tumors that are otherwise deemed irresectable.

Liver venous deprivation compared to portal vein embolization to induce hypertrophy of the future liver remnant before major hepatectomy: A single center experience

BackgroundTo assess the safety and efficacy of liver venous deprivation (simultaneous hepatic vein embolization with portal vein embolization) compared with portal vein embolization alone before major hepatectomy in patients with small future liver remnant. MethodsWe assessed all consecutive patients who underwent ipsilateral liver venous deprivation before major hepatectomy (>4 Couinaud’s segments) at the University Hospital Lausanne from 2016 to 2018. Postembolization, volumetric analysis after liver venous deprivation and postoperative outcomes were compared with patients who underwent portal vein embolization alone (portal vein embolization group) from 2010 to 2016. ResultsDuring the study period, 21 patients underwent liver venous deprivation and 39 portal vein embolization alone. In the liver venous deprivation versus portal vein embolization groups, dropout rate owing to disease progression was 1 of 21 vs 9 of 39 (P = .053). There were no per procedural complications after liver venous deprivation and no difference in the postoperative outcomes. Future liver remnant hypertrophy was greater in the liver venous deprivation group (median 135%, interquartile range: 123%–154%) than in the portal vein embolization group (median 124%, interquartile range: 107%–140%) at a median time of 22 days after liver venous deprivation vs 26 days after portal vein embolization (P = .034). The median kinetic growth rate was also greater (2.9%/week, interquartile range: 1.9–4.3% vs 1.4%/week, interquartile range: 0.7–2.1%; P < .001). ConclusionIpsilateral liver venous deprivation before major hepatectomy is safe and seems to induce a greater and faster future liver remnant hypertrophy than after portal vein embolization alone. More data are needed to analyze the impact of liver venous deprivation on tumor growth.

Right-side versus left-side hepatectomy for the treatment of hilar cholangiocarcinoma: a comparative study

BackgroundRadical resection is the only curative treatment for patients with hilar cholangiocarcinoma. While left-side hepatectomy (LH) may have an oncological disadvantage over right-side hepatectomy (RH) owing to the contiguous anatomical relationship between right hepatic inflow and biliary confluence, a small future liver remnant after RH could cause worse surgical morbidity and mortality. We retrospectively compared surgical morbidity and long-term outcome between RH and LH to determine the optimal surgical strategy for the treatment of hilar cholangiocarcinoma.MethodsThis study considered 83 patients who underwent surgical resection for hilar cholangiocarcinoma between 2010 and 2017. Among them, 57 patients undergoing curative-intent surgery including liver resection were enrolled for analysis—33 in the RH group and 27 in the LH group. Prospectively collected clinicopathologic characteristics, perioperative outcomes, and long-term survival were evaluated.ResultsPortal vein embolization was more frequently performed in the RH group than in the LH group (18.2% vs. 0%, P = 0.034). The proportion of R0 resection was comparable in both groups (75.8% vs. 75.0%, P = 0.948). The 5-year overall and recurrence-free survival rates did not differ between the groups (37.7% vs. 41.9%, P = 0.500, and 26.3% vs. 33.9%, P = 0.580, respectively). The side of liver resection did not affect long-term survival. In multivariate analysis, transfusion (odds ratio, 3.12 [1.42–6.87], P = 0.005) and post-hepatectomy liver failure (≥ grade B, 4.62 [1.86–11.49], P = 0.001) were independent risk factors for overall survival.ConclusionsWe recommend deciding the side of liver resection according to the possibility of achieving radical resection considering the anatomical differences between RH and LH.

How should liver hypertrophy be stimulated in the settings of colorectal liver metastases? - Comparison of upfront ALPPS and PVE with rescue possibility

Background: Since the introduction of ALPPS there has been an intense debate about the appropriateness of the procedure and some have argued that portal vein embolization (PVE) should remain the standard of care in the situation of inadequate future liver remnant (FLR). The main aim of this study was to compare successful resection rate with upfront associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) compared to PVE with rescue ALPPS on demand. Material and Methods: A retrospective analysis of all patients with standardized FLR (sFLR) =30% treated with PVE or ALPPS for colorectal liver metastases at five Scandinavian university hospitals during the years 2013-2016. Liver volumes, oncological treatment, procedures and complications were gathered. Chi-square test and Mann-Whitney U test was used to assess differences between the two groups. Successful resection rate was defined as completed liver resection without 90-day mortality. Results: A total of 165 patients (96% treated with neoadjuvant chemotherapy) was found, 64 treated with up front ALPPS (group A) and 101 treated primarily with PVE (group B), of which 20 had rescue ALPPS. There were 111 male and 54 female patients with median sFLR 21% before start of treatment. Age, sFLR, the use of chemotherapy, number and size of largest tumour was the same in both groups. In group A 88% and in group B 73% had successful resections (p=0.03). The hypertrophy of the FLR in group A was 67% compared to 90% total hypertrophy (after PVE and rescue ALPPS) in rescue ALPPS (p=0.06). Conclusion: Upfront ALPPS seems to offer higher percentage successful resections than PVE with rescue ALPPS as an addition on demand. The sequential combination of PVE and ALPPS may lead to higher degree of hypertrophy than upfront ALPPS and may therefore be the appropriate choice of treatment in very small FLR.

Dealing with insufficient liver remnant: Associating liver partition and portal vein ligation for staged hepatectomy.

Liver resection for colorectal liver metastases has emerged to highly successful treatment in the last decades. Key to this success is complete hepatic tumor removal and systemic disease control by chemotherapy. Associating liver partition and portal vein ligation for staged hepatectomy is the most recent two-stage resection strategy for patients with very small future liver remnant making complete tumor removal possible within 1 to 2 weeks. Oncological outcome data are being collected at the moment and first results from small series reveal promising results.

Characterization of early recurrences following liver resection by ALPPS and two stage hepatectomy in patients with colorectal liver-metastases and small future liver remnants; a translational substudy of the LIGRO-RCT

BackgroundAssociated liver partition and portal vein ligation in staged hepatectomy (ALPPS) is an alternative resection method to portal vein embolization (PVE) in patients with small future liver remnants (FLR) but has been associated with early tumor recurrences. MethodsTwenty-four patients with colorectal liver metastases (CRLM) patients from the randomized multicenter LIGRO trial comparing outcome of ALPPS (n = 13) vs PVE (n = 11) were included in the study. Mutational analyses of the KRAS, NRAS, BRAF, PIC3CA and TP53 genes of the metastases were performed in 21 patients and correlated to early tumor recurrence. ResultsWithin 12 months, 13 patients experienced recurrences (6 in TSH group and 7 in ALPPS group). Nine of 13 patients with recurrences had mutations in the TP53 gene, while 3 of 8 patients without recurrence carried the same mutation. Only sporadic cases of the other mutations studied were identified. ConclusionsALPPS did not appear to be associated with higher rate of rapid recurrences than PVE following radical resection of colorectal liver metastases. Mutations in genes associated with negative oncologic outcome after surgical resection most likely play a role for tumor recurrences in these patients.

ALPPS in overcoming small remnant liver volume in alveolar echinococcosis

Aim.To evaluate the possibilities and indications for ALPPS, immediate and long-term results of surgical treatment of alveolar echinococcosis including great vessels invasion in case of small remnant liver volume.Material and methods. There were 30 ALPPS procedures. Seven patients had small future liver remnant (FLR) — 24.5% (22.4—26.7%). Bile ducts repair with Roux-en-Y procedure for biliodigestive anastomosis during the first surgical stage was performed in 5 patients (71.4%). ALPPS combined with great vessels resection (portal vein or portal vein and left hepatic vein) was required in 4 patients (57.1%). RO-resections were carried out in all patients.Results.Mean duration of ALPPS stage I was 365 (330—415) min, intraoperative blood loss — 800 (700—1000) ml. Time of stage II was 85 (70—110) min, intraoperative blood loss — 200 (100—300) ml. The second stage of ALPPS was performed in 6—7 days (max 8 days) after preliminary assessment of FLR volume according to CT-volumetry, which was 570 (430—630) ml (37.9% (31.9—52.4%) in relation to FLR volume before the first stage of ALPPS. Augmentation of FLR volume was 200 (150—290) ml (60.9% (48.3—80.6%)). The daily increase of FLR volume was 29 (23—46) ml. Overall postoperative morbidity was 42.9% (complications grade I were noted in 2 patients (28.6%), grade IV — in 1 patient (14.3%). Incidence of post-hepatectomy liver failure grade A (ISGLS, 2011) after ALPPS stage II was 42.9% (n = 3). Bile leakage grade A (ISGLS, 2011) occurred in 28.6% of cases (n = 2). Mortality was absent. Postoperative hospital-stay after stage II was 22 (18—35) days. Maximum follow-up was 50 months. Long-term disease-free survival was 100%, median survival — 29 months.Conclusion.ALPPS technique is feasible, followed by desired increase of FLR volume and safe hepatectomy. The procedure leads to good immediate and long-term postoperative results in patients with alveolar echinococcosis and small FLR volume regard less invasion of afferent and/or efferent liver vessels.

ALPPS for primary and metastatic liver cancer: the results of single-center study

Background: The main goal was to assess safety and outcomes of ALPPS procedure and find the optimal compromise between dropout and mortality risk, using our initial single-center experience Methods: 20 patients who have underwent ALPPS resection at the Abdominal Oncology Department from Jan 2012 to Jun 2016 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify independent risk factors for severe complications, mortality and volume growth of the FLR Results: Mean age was 59,1±6,3(49 -72)years. Indications for surgical resection were CRLM in 80% and HCC in 20% cases. 1 patient had salvage ALPPS after failed PVL. Patients were operated for 2.8±1.6 metastases, the largest was 64.6±18.8 mm.The increase in FLR between the 2 steps was 95.3±53.6% (range: 13-164%, p<0.001).The average time between steps of the procedure was 9.4±1.4 days. Severe complications including mortalities (Clavien-Dindo≥IIIb) occurred in 6,7 and 9,1% of patients after ALPPS-1 and 2 resp. Follow-up mediana was 20 mo. Mean OS rate was 26,1 [22,5-29,6]mo. Mean DFS rate 24,1 [19,6-28,5]mo.Primary liver cancer, age, histologic changes of liver parenchyma, led to morbidity and mortality rate Conclusion: ALPPS should be reserved to a small proportion of patients, the young ones with very small future liver remnant, with the low rate of liver function reserve or experiencing inadequate hypertrophy after portal vein occlusion. For these patients ALPPS could still offer a benefit, being the only chance of resectability

Comparison of RALLPS, portal vein embolisation(PVE) and portal vein ligation(PVL) in prevention of posthepatectomy liver failure

Background: Different surgical strategies are used for prevention of posthepatectomy liver failure. Aim of the study was to compare of radiofrequensy ALLPS(RALLPS), PVE and PVL in prevention of posthepatectomy liver failure in single center. Methods: In Moscow Clinical Scientific Center(between January 2014 and December 2016) 23 PVE, 7 PVL, 8 RALPPS (3 RALLPS+PVL and 5 transcutaneous RALLPS +PVE) patients(pts) were included. Indication for PVE were less than 30% (normal liver), or 40% (cirrhotic liver) preoperative estimated future liver remnant (FLR). Indications for ALPPS/RALPPS were: very small FLR (less than 20%). CT volumetry and 99m Tc-Mebrofenin SPECT/CT were performed to estimate FLR volume and function. Results: Duration after first stage was significantly shorter in RALPPS (10 days) in comparison with two-stage hepatectomy with PVE (29 days) and PVL(35 days). The rate of hypertrophy of FRL was significantly higher after first stage of RALPPS (66.3%) in comparison with PVE (27.2%) and PVL(20%). Tumor progression was revealed in 7 (30%) pts after PVE, in 3(42%) and in 0 (0%) after RALPPS (p>0.05). Liver failure according to ISGLS criteria was revealed in 5 (22%) pts after PVE (grade А, В), 1(12,5%) after PVL(Grade B) and 1 (12,5%) pts after RALPPS (grade В) without significant differences (p>0,05). Conclusion: Variants of RALPPS are effective in prevention of posthepatectomy liver failure with lower rate of morbidity and tumor progression comparable with two-stage hepatecomies.

Posthepatectomy liver failure in patients with perihilar cholangiocarcinoma

Introduction: Posthepatectomy liver failure (PHLF) after radical treatment of perihilar cholangiocarcinoma (PHCC) is still high. We aimed to evaluate the factors affecting PHLF after radical resections for PHCC. Method: From October 2013 to December 2018, 100 patients underwent radical resection with intention-to-treat. Open and minimally invasive (laparoscopic and robot-assisted) resection with regional lymphadenectomy D2 were performed. Mann-Whitney U-test was used for statistical analysis. Result: Three patients were treated for benign strictures (PHCC was not confirmed on pathology). Further, only patients with PHCC were included analyzed. Demographic and perioperative data: female/male ratio 51/46; mean age 60 (35-80) year; ASA 4 (2-5); acute cholangitis after biliary drainage 56 (58%); portal vein embolization 22 (23%); vascular reconstruction 32 (33%); blood loss 505 (50-2500) mL; operation time 567 (290-985) min. PHLF took place in 19 (20%) of patients, including 11 and 8 cases of grade B and C (ISGLS), respectively. The whole mortality was 16 (16%); mortality in PHLF group was 5 (31%). Severe morbidity (>II Clavien-Dindo) was registered in 77 (79%) patients. R0 resection rate was 85%; hospital stay 24 (3-73) day. Portal vein embolization (PVE) was performed in 24 patients (25%). The influence of 22 factors on the risk of PHLF was analyzed. PHLF significantly dependent on blood loss (p=0,033), blood transfusion (p=0,017), resection of >3 liver segments (p=0,045). PHLF did not significantly increase the hospital stay. Conclusion: The high risk of PHLF should be considered after major liver resection and large blood loss. PVE in case of small future liver remnant and effective treatment of preoperative cholangitis are necessary to reduce the risk of PHLF.

The ALPPS procedure: hepatocellular carcinoma as a main indication. An Italian single-center experience.

The ALPPS is a technique that allows achieving hepatic resection by a rapid future liver remnant hypertrophy. The aim of this study was to report the experience of an Italian center with ALPPS in patients with liver tumors. A retrospective analysis of patients undergoing ALPPS between 2012 and 2017 was performed. Patients' characteristics and disease presentation, increase in future liver remnant (FLR) as well as intraoperative and postoperative short- and long-term outcomes were evaluated. A total of 24 patients underwent the ALPPS procedure: 17 procedures for hepatocarcinoma (HCC), 5 for colorectal liver metastases (CRLM), 1 for cholangiocarcinoma (CC) and 1 for Merkel Cell Carcinoma liver metastasis (MCCLM). Macrovascular invasion (MVI) was recorded in 10 (41.6%) patients: 8 (33.3%) patients with HCC had invasion of portal vein (5), middle hepatic vein (2) and inferior vena cava (1). One patient with CRLM had involvement of middle hepatic vein and one patient with CC had involvement of right portal vein and middle hepatic vein. A p-ALPPS in 14 cases (58.3%), 10 t-ALPPS (41.6%) and hanging maneuver in 19 patients (80%) were performed. Median postoperative stay was 26days (range 16-68days). 90-day mortality was 8.3% (two patients, one with CC and one with HCC), 90-day mortality for HCC was 5.8%. After stage 1, we counted 15 complications all of grade I; after stage 2 the number of complications was increased to 37:33 were of grade I and 4 were of grade IV. R0 resection was achieved in all patients with 100% oncology feasibility. After a median follow-up of 10months (range 2-54), disease recurrence has been recorded in 6 patients with HCC and in 2 with CRLM. Eleven patients died, nine affected by HCC, one by CRLM, and one by CC. 2-years OS and disease-free survival (DFS) for the entire group were 47.3% and 47.5%, respectively. Concerning patients operated on for HCC, the 2-years OS and DFS were 38.5% and 60%, respectively. The ALPPS procedure is an interesting approach for large primary or secondary liver tumor with small FLR above all for large HCC associated with MVI, with acceptable OS and DFS.

Characterization of early recurrences following liver resection by ALPPS and two stage hepatectomy (TSH) in patients with colorectal liver-metastases and small future liver remnants (FLR)

Background: Surgical resection is the only curative treatment option for patients with CRLM. Novel therapeutic strategies therefore aim at offering surgery to patients outside traditional resection criteria. In patients with small FLR, ALPPS is described as an alternative to TSH but initial reports suggested higher rates of early recurrences. This study aims at identifying clinical and biological factors associated with early recurrences following liver resection by ALPPS and TSH in patients with colorectal liver-metastases (CRLM). Materials and methods: All patients included at one site participating in the LIGRO study* were included (n = 43). Twenty-three patients were randomized to PVE and 20 to ALPPS. Cross-over to rescue surgery by ALPPS was allowed (n = 4). Three patients were excluded for inoperability. Thus, 16 liver resections were completed by TSH and 24 by ALPPS. Tumor samples were analyzed for KRAS, BRAF, NRAS, PIK3CA and TP53 gene mutations. Results: A similar fraction (25%) in each group developed recurrent liver metastases within one year after resection. Rapid recurrences were not associated with primary tumor location or liver resection margin. The mutation status of RAS/RAF/PIK3CA genes were comparable in patients with and without recurrences. All coding sequences of TP53 were investigated for 6 samples with recurrence; the 4 with mutation were all found in the ALPPS group. Conclusion: ALPPS was not associated with a higher rate of early recurrences than TSH in this randomized setting. Early recurrences were not conclusively associated with specific mutational patterns. Long term survival analysis for the entire cohort is ongoing.

Comparison of CT and hepatobiliary scintigraphy in volumetry of future liver remnant after portal vein embolization and RALPPS

Background: The study was aimed to compare accuracy of CT and hepatobiliary scintigraphy (HBS) in volumetric estimation of future liver remnant (FLR) before and after portal vein embolization (PVE) and Radiofrequency Assisted Liver Partition with Portal vein embolization in Staged liver resection (RALPPS). Methods: During three years (January, 2015-December, 2017) 46 patients with different malignancies of liver and bile ducts included in the study: PVE (29) and RALLPS (17) were performed when major liver resection was indicated in patients with small FLR. Results: After PVE alone the mean rate of FLR hypertrophy estimated by HBS was significantly larger than the mean rate estimated by CT-volumetry: 71(20-171)% and 31(10-97)%, respectively (p=0,001). After RALPPS the mean rate of FLR hypertrophy estimated by HBS was also significantly larger than the mean rate estimated by CT-volumetry: 86(25-264)% and 45 (0-113)%, respectively (p=0,027). There was no significant differences in the rate of FLR hypertrophy between PVE and RALPPS, estimated by CT (p=0,099) and HBS (p=0,471). Conclusion: HBS is more effective and more precise method of FLR volumetry in comparison with CT-volumetry as HBS considers volumetry of functioning liver parenchyma. In terms of FLR hypertrophy RALPPS did not show evident advantage over PVE, nevertheless, there was a tendency to more effectiveness of RALPPS.

Role of associating liver partition and portal vein ligation in staged hepatectomy (ALPPS)-strategy for colorectal liver metastases.

Colorectal carcinoma (CRC) is the third leading cause of cancer-related death in the United States. The liver is the most frequent site of metastasis and a key determinant of survival in patients with isolated colorectal liver metastasis (CRLM). Surgical resection remains the only hope for prolonged survival in patients with CRLM. However, most patients are deemed to be unresectable at presentation due to a small future liver remnant (FLR) and fear of post-hepatectomy liver failure. Procedures such as portal vein ligation or embolization (PVL/PVE) followed by hepatectomy have been established as standard methods to increase FLR volume, but have limitations dependent upon extent of disease and patient's ability to grow the liver remnant. Recently, associating liver partition and portal vein ligation in staged hepatectomy (ALPPS) has been introduced as a technique to induce liver hypertrophy over a shorter time period. Being a complex two-stage surgical procedure, initial reports of higher ALPPS-associated complications and mortality limited its worldwide adoption by hepatobiliary surgeons. However, recent studies have showed ALPPS superiority over conventional procedures in terms of feasibility and inducing liver hypertrophy, with comparable morbidity and mortality. We herein review the role of ALPPS in management of patients with CRLM.