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Two‐stage hepatectomy (TSH) is one of the specific surgical techniques that can expand the pool of resectable patients with initially unresectable colorectal liver metastases (CRLM). The indication of TSH for CRLM is only bilateral, multinodular disease, which cannot be resected by a single hepatectomy. TSH is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long‐term outcomes. However, not all eligible patients can benefit from the TSH strategy. One of the most important issues is dropout from the strategy (failure to complete both of the two sequential procedures), because the survival of such patients is drastically worse compared with patients who can complete both stages. Another important issue is the early recurrence rate and subsequent poor survival even after completion of TSH. Thus, the selection of appropriate patients who can really benefit from the TSH strategy is crucial. This review discusses the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM., Although two‐stage hepatectomy (TSH) for extensive colorectal liver metastases (CRLM) is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long‐term outcomes, not all eligible patients can benefit from this strategy. In this review, we discuss the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM.

Two-stage liver resections were described to increase the resectability of liver tumors in patients with insufficient future liver remnant. The ALPPS procedure, described in 2011, has represented a breakthrough in the field of hepato-pancreato-biliary surgery. This technique accelerates the hypertrophy of the future liver remnant and reduces the interval between the two surgeries compared with previous techniques. ALPPS has gained popularity rapidly, with more than 1200 patients included in the world registry. Recommendations about indications, patient selection and surgical standardization have been discussed twice in international expert meetings. Although ALPPS has proven to be superior in terms of resectability (80-100% versus 60-90% of twostage hepatectomy), its rapid implementation has been punished with high morbidity and mortality reaching up to 40% and 9%, respectively, in the published series. The current evidence on the possible benefits and disadvantages is mainly based on observational studies. We present a historical review, describing the different technical modifications that have been carried out since its description, with a rigorous review in terms of morbidity, mortality, and oncological outcomes.

BACKGROUND: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management and outcomes of patients completing TSH in major hepato-biliary centers in the United States. METHODS: A retrospective review from 5 liver centers in the United States identified patients who completed a TSH procedure for bilateral CRLM. RESULTS: From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed with an open technique (n = 194, 99.5%). The median number of tumors was 7 (range, 2–33). One-hundred twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival was 50 months with a median follow-up of 28 months (range, 2–143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar overall survival (OS) to those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complications rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). Overall survival was significantly decreased by positive resection margins and increased estimated blood loss (EBL) (p = 0.036 and p = 0.05, respectively). CONCLUSION: This is the largest TSH series in the U.S. and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.

Since first described, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has garnered boisterous praise and fervent criticism. Its rapid adoption and employment for a variety of indications resulted in high perioperative morbidity and mortality. However recent risk stratification, refinement of technique to reduce the impact of stage I and progression along the learning curve have resulted in improved outcomes. The first randomized trial comparing ALPPS to two stage hepatectomy (TSH) for colorectal liver metastases (CRLM) was recently published demonstrating comparable perioperative morbidity and mortality with improved resectability and survival following ALPPS. In this review, as ALPPS enters the thirteenth year since conception, the current status of this contentious two stage technique is presented and best practices for deployment in the treatment of CRLM is codified.

Abstract Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and two stage hepatectomy with inter-stage portal vein embolization (TSH/PVE) are surgical maneuvers applied in patients with advanced malignancies considered unresectable by means of conventional liver surgery. The aim of this report is to compare the oncologic outcome and technical feasibility of ALPPS and TSH/PVE in the scenario of colorectal liver metastases (CRLM). Methods All consecutive patients who underwent either ALPPS or TSH/PVE for CRLM between 2011 and 2017 in one hepatobiliary center were analyzed and compared regarding perioperative and long-term oncologic outcome. Results A cohort of 58 patients who underwent ALPPS (n = 21) or TSH/PVE (n = 37) was analyzed. The median overall survival (OS) was 28 months and 34 months after ALPPS and TSH/PVE (p = 0.963), respectively. The median recurrence-free survival (RFS) was higher following ALPPS with 19 months than following TSH/PVE with 10 months, but marginally failed to achieve statistical significance (p = 0.05). There were no differences in morbidity and mortality after stages 1 and 2. Patients undergoing ALPPS due to insufficient hypertrophy after TSH/PVE (rescue-ALPPS) displayed similar oncologic outcome as patients treated by conventional ALPPS or TSH/PVE (p = 0.971). Conclusions ALPPS and TSH/PVE show excellent technical feasibility and comparable long-term oncologic outcome in CRLM. Rescue ALPPS appears to be a viable option for patients displaying insufficient hypertrophy after a TSH/PVE approach.

International audience; BACKGROUND:Two-stage hepatectomy of bilobar colorectal liver metastases is widely used and shows encouraging survival results. However, the risk of dropout after the first stage remains high and is associated with poor survival. The objective of our study was to evaluate the factors associated with long-term survival based on the pathologic response to preoperative systemic chemotherapy in colorectal liver metastases patients who underwent two-stage hepatectomy.METHODS:The pathologic response to preoperative chemotherapy and its effect on second-stage completion and survival were retrospectively evaluated in 67 patients treated between 2003 and 2013.RESULTS:A total of 56 patients underwent two-stage hepatectomy for initially nonresectable colorectal liver metastases. Chemotherapy was combined with a biotherapy in 32 cases. The tumor regression grade, modified tumor regression grade, and Blazer grade were used to classify patients as responders (tumor regression grade and modified tumor regression grade 1-3, Blazer 0-1) or nonresponders (tumor regression grade and modified tumor regression grade 4-5, Blazer 2) after the first stage. Tumor response in the three classifications was associated with second-stage completion (tumor regression grade 1-3: OR = 4.01, 95% CI: 1.12-14.36, P = .033; modified tumor regression grade 1-3: OR = 3.8, 95% CI: 1.13-12.6, P = .03; Blazer 0-1: OR = 5.45, 95% CI: 1.66-17.85, P = .005). Triple chemotherapy was also associated with responders. The median overall survival of responders was significantly higher (Blazer 0-1: 42.9 months versus Blazer 2: 20.1 months, P = .018; tumor regression grade 1-3: 42.9 months versus tumor regression grade 4-5: 25.1 months, P = .04).CONCLUSION:A pathologic response to chemotherapy is associated with second-stage completion and longer survival. Further studies are needed to achieve the early identification of patients for whom the benefit of the second surgical stage is less straightforward.

Colorectal liver metastases (CLM) are not always resectable at the time of diagnosis. An insufficient future liver remnant is a factor excluding patients from curative intent resection. To deal with this issue, two-stage hepatectomy was introduced approximately 20 years ago. It is a sequential treatment strategy for bilateral CLM, which consists of preoperative chemotherapy, portal vein embolization, and planned first and second liver resections. This study reviews current evidence supporting use of two-stage hepatectomy.

Bakground: Two-stage hepatectomy (TSH) with portal vein embolization (PVE) is associated with high morbidity and mortality and may result in liver failure due to insufficient future liver remnant. The objectives of this investigation were to evaluate the short-term outcomes of patients with colorectal cancer liver metastasis who underwent TSH with PVE, and to critically review the selection criteria for TSH-PVE. Methods: A retrospective review of all patients who were operated due to bi-lobar CRLM during the years 2007–2017 was performed. Patients who underwent TSH-PVE were compared to those who underwent right hepatectomy (RH) only. Results: Twenty-nine patient underwent TSH, 25 of whom (86.2%) completed both stages. These patients demonstrated a major complication rate of 17%, and a 90-day mortality rate of 3.4%. Most complications (80%) were related to the colonic resection, and one patient developed liver failure. Patients who suffered complications had a trend towards more baseline comorbidities and more liver lesions. Ablative techniques were utilized in 76%. When compared to 35 patients who underwent sole RH, no significant difference was demonstrated in major complication rate (20%) or mortality (0%). Conclusions: TSH is a relatively safe procedure in selected patients. Ablative techniques can reduce the occurrence of liver insufficiency and should be used liberally when possible. Factors such as number of lesions, comorbidities and the timing of colonic resection should be considered and evaluated in order to improve the outcomes of the procedure.

Background: Hepatectomy in patients with large tumor load may result in postoperative liver failure and associated complications due to excessive liver parenchyma removal. Conventional two-stage hepatectomy (TSH) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique are possible solutions to this problem. Colorectal liver metastases (CRLM) is the most frequent indication, and there is a need to assess outcomes for both techniques to improve surgical and long-term oncological outcomes in these patients. Methods: A single-center retrospective study was designed to compare TSH with ALPPS in patients with initially unresectable bilateral liver tumors between January 2005 and January 2020. ALPPS was performed from January 2012 onwards as the technique of choice. Long-term overall survival (OS) and disease-free survival (DFS) were evaluated as primary outcome in CRLM patients. Postoperative morbidity, mortality and liver growth in all patients were also evaluated. Results: A total of 38 staged hepatectomies were performed: 17 TSH and 21 ALPPS. Complete resection rate was 76.5% ( n = 13) in the TSH group and 85.7% ( n = 18) in the ALPPS group ( P = 0.426). Overall major morbidity (Clavien-Dindo >= 3a) (stage 1 + stage 2) was 41.2% ( n = 7) in TSH and 33.3% ( n = 7) in ALPPS patients ( P = 0.389), and perioperative 90-day mortalities were 11.8% ( n = 2) vs. 19.0% ( n = 4) in each group, respectively ( P = 0.654). Intention-to-treat OS rates at 1 and 5 years in CRLM patients for TSH ( n = 15) were 80% and 33%, and for ALPPS ( n = 17) 76% and 35%, respectively. DFS rates at 1 and 5 years were 36% and 27% in the TSH group vs. 33% and 27% in the ALPPS group, respectively. Conclusions: ALPPS is an effective alternative to TSH in bilateral affecting liver tumors, allowing higher resection rate, but patients must be carefully selected. In CRLM patients similar long-term OS and DFS can be achieved with both techniques. (c) 2021 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.

Colorectal liver metastases (CRLM) affect over 50 % of all patients with colorectal cancer, which is the second leading cause of cancer in the western world. Resection of CRLM may provide cure and improves survival over chemotherapy alone. However, resectability of CLRM has to be decided in multidisciplinary tumor boards and is based on oncological factors, technical factors and patient factors. The advances of chemotherapy lead to the abolition of contraindications to resection in favor of technical resectability, but somatic mutations and molecular subtyping may improve selection of patients for resection in the future. Technical factors center around anatomy of the lesions, volume of the remnant liver and quality of the liver parenchymal. Multiple strategies have been developed to overcome volume limitations and they are reviewed here. The least investigated topic is how to select the right patients among an elderly and frail patient population for the large variety of technical options specifically for bi-lobar CRLM to keep 90-day mortality as low as possible. The review is an overview over the current state-of-the art and a systematic guide to the topic of resectability of CRLM for both clinicians and patients.

Background: Pushing the surgical limits for initially unresectable colorectal liver metastases (CRLM) are two approaches for sequential liver resection: two-stage hepatectomy (TSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS). However, the role of each treatment modality remains ill-defined. The present meta-analysis was designed to compare the safety, efficacy, and oncological benefits between ALPPS and TSH in the management of advanced CRLM.Methods: A systematic literature search was conducted from online databases through to February 2020. Single-arm synthesis and cumulative meta-analysis were performed.Results: Eight studies were included, providing a total of 409 subjects for analysis (ALPPS: N = 161; TSH: N = 248). The completions of the second stage of the hepatectomy [98 vs. 78%, odds ratio (OR) 5.75, p < 0.001] and R0 resection (66 vs. 37%; OR 4.68; p < 0.001) were more frequent in patients receiving ALPPS than in those receiving TSH, and the waiting interval was dramatically shortened in ALPPS (11.6 vs. 45.7 days, weighted mean difference = −35.3 days, p < 0.001). Nevertheless, the rate of minor complications was significantly higher in ALPPS (59 vs. 18%, OR 6.5, p < 0.001) than in TSH. The two treatments were similar in 90-day mortality (7 vs. 5%, p = 0.43), major complications (29 vs. 22%, p = 0.08), posthepatectomy liver failure (PHLF; 9 vs. 9%, p = 0.3), biliary leakage (11 vs. 14%, p = 0.86), length of hospital stay (27.95 vs. 26.88 days, p = 0.8), 1-year overall survival (79 vs. 84%, p = 0.61), 1-year recurrence (49 vs. 39%, p = 0.32), and 1-year disease-free survival (34 vs. 39%, p = 0.66). Cumulative meta-analyses indicated chronological stability for the pooled effect sizes of resection rate, 90-day mortality, major complications, and PHLF.Conclusions: Compared with TSH, ALPPS for advanced CRLM resulted in superior surgical efficacy with comparable perioperative mortality rate and short-term oncological outcomes, while this was at the cost of increased perioperative minor complications.

Whether resection of recurrent colorectal cancer liver metastases (CLMs) can be safely performed after prior hepatectomy, especially after two-stage hepatectomy (TSH), and to what extent this aggressive surgical approach may impact patient outcomes and prolong survival, are important issues to investigate.

The safety and feasibility of laparoscopic, two-stage hepatectomy for bilobar colorectal liver metastases is poorly evaluated.We reviewed retrospectively 86 consecutive patients who underwent complete two-stage hepatectomy (left lobe clearance as the first stage and standard/extended right hepatectomy as the second stage) for bilobar colorectal liver metastases between 2007 and 2017 in 2 tertiary centers. Short- and long-term outcomes were compared between laparoscopic and open two-stage hepatectomy before and after propensity score matching.Laparoscopic two-stage hepatectomy was performed in 38 patients and open two-stage hepatectomy in 48. After propensity score matching, 25 laparoscopic and 25 open patients showed similar preoperative characteristics. For the first stage, a laparoscopic approach was associated with lesser hospital stays (4 vs 7.5 days; P.001). For the second stage, a laparoscopic approach was associated with less blood loss (250 vs 500 mL; P = .040), less postoperative complications (32% vs 60%; P = .047), lesser hospital stays (9 vs 16 days; P = .013), and earlier administration of chemotherapy (1.6 vs 2 months; P = .039). Overall survival, recurrence-free survival, and liver-recurrence-free survival were comparable between the groups (3-year overall survival: 80% vs 54%; P = .154; 2-year recurrence-free survival: 20% vs 18%; P = .200; 2-year liver-recurrence-free survival: 39% vs 33%; P = .269). Although both groups had comparable recurrence patterns, repeat hepatectomies for recurrence were performed more frequently in the laparoscopic two-stage hepatectomy group (56% vs 0%; P = .006).Laparoscopic two-stage hepatectomy for bilobar colorectal liver metastases is safe and feasible with favorable surgical and oncologic outcomes compared to open two-stage hepatectomy.

This chapter reviews the history, indications, and outcomes of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Various operative techniques are described, considerations for management of patients during the interstage period are discussed, and current evidence on short- and long-term outcomes following ALPPS performed in patients with colorectal liver metastases is summarized. Specific recommendations regarding patient selection and operative technique are offered.

BACKGROUND: Recurrence rates are high for patients who have undergone two-stage hepatectomy (TSH) for bilateral colorectal liver metastases, and there is no established treatment approach for recurrent disease. This study aimed to determine the feasibility, safety, and prognostic impact of surgical resection for recurrence after TSH and the prognostic role of RAS mutation in this cohort. METHODS: The study included 137 patients intended to undergo TSH for bilateral colorectal metastases during 2003–2016. Clinicopathologic factors were compared using univariate and multivariate analysis. RESULTS: One hundred eleven patients (81%) completed TSH. The median recurrence-free survival in these patients was 12 months. Of the 83 patients with subsequent recurrence, 31 (37%) underwent resection for recurrence, and 11 underwent multiple resections for recurrence. Forty-eight operations were performed for recurrence: 23 repeat hepatectomies, 14 pulmonary resections, 5 locoregional resections, and 6 concurrent resections in multiple organ sites. The median overall survival (OS) among patients with recurrence was 143 months for patients who underwent resection and 49 months for those who did not (P

Background: Two-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal metastases (CLM). As alternative, ultrasound-guided one-stage hepatectomy (E-OSH) has been proposed even for deep-located nodules to compare TSH and E-OSH. Methods: All consecutive TSH at the Paul Brousse Hospital and E-OSH at the Humanitas Research Hospital were considered. The inclusion criteria were ≥6 CLM, ≥3 CLM in the left liver, and ≥1 lesion with vascular contact. A total of 74 TSH and 35 E-OSH were compared. Results: The 2 groups had similar characteristics. Drop-out rate of TSH was 40.5%. In comparison with the cumulated hepatectomies of TSH, E-OSH had lower blood loss (500 vs. 1,100 mL, p = 0.009), overall morbidity (37.1 vs. 70.5%, p = 0.003), severe morbidity (14.3 vs. 36.4%, p = 0.04), and liver-specific morbidity (22.9 vs. 40.9%, p = 0.02). R0 resection rate was similar between groups. E-OSH and completed TSH had similar overall survival (5-year 38.2 vs. 31.8%), recurrence-free survival (3-year 17.6 vs. 17.7%), and recurrence sites. Conclusions: E-OSH is a safe alternative to TSH for multiple bilobar deep-located CLM. Whenever feasible, E-OSH should even be considered the preferred option because it has excellent safety and oncological outcomes equivalent to completed TSH, without the drop-out risk.

Purpose of review To review the role of liver transplantation for unresectable colorectal liver metastases (u-CRLM) and to describe the intial experience with auxiliary living donor liver transplantation combined with two-stage hepatectomy for u-CRLM (i.e. living donor RAPID). Recent findings Patients affected with u-CRLM have a poor prognosis with 5 years overall survival (OS) rate less than 10% under standard modern chemotherapy.There is an actual international consensus that liver transplantation for u-CRLM represents a viable option in highly selected patients with OS rate at 5 years up to 80% notwithstanding high recurrence rates. Due to the scarcity of whole liver graft from deceased donors, the RAPID procedure (i.e. resection and partial liver segment 2-3 transplantation from deceased donors with delayed total hepatectomy) has been introduced as possible alternative. The RAPID procedure represents the most actual and modern fusion of the two most challenging procedures of modern hepatobiliary and liver transplant surgery: that is auxiliary partial orthotopic liver transplantation and associating liver partition and portal vein ligation for staged hepatectomy. Although the deceased donor-RAPID procedure may show promising results, the basic problem of scarcity of organs from deceased donors and mainly the lack of splittable organs still remains. Summary The living donor RAPID, based on transplantation of left lateral segments from living donor, may represent the way out to this problem. It is feasible and safe (for both donor and recipient), but characterized by a very challenging high-end transplantological procedure.

Major vascular involvement often constitutes a contraindication to the laparoscopic approach. Lopez-Ben and colleagues described a purely laparoscopic surgical technique consisting of two stages, eight weeks apart, utilizing the caudal view and proximal approach for complete removal of colorectal liver metastases in close proximity to all three hepatic veins.

To compare the overall survival (OS) and disease-free survival (DFS) of Tourniquet-ALPPS (T-ALPPS) and conventional two-stage hepatectomy (TSH) in patients with colorectal liver metastases (CRLM). A retrospective study from a prospectively collected database was performed between October 2000 and July 2016. TSH was performed before September 2011, after which time T-ALPPS became the technique of choice. A propensity score matching (PSM) was performed based on a 1:1 ratio with consideration of the following variables: number and size of metastases, bilobar disease presence, and chemotherapy received. Thirty-four patients received T-ALPPS; 41 patients received TSH. After PSM, 21 patients remained in each group, with 100% resectability in the T-ALPPS group and 90.5% resectability in the TSH group. The median OS for TSH was 41 months; for T-ALPPS, the median OS was 36 months (P = 0.925). The median DFS was 16 months in the TSH group; the median DFS was 9 months in the T-ALPPS group (P = 0.930). The 1-, 3-, and 5-year OS for TSH was 81%, 66.7%, and 23.8% vs. 76.2%, 57.1%, and 22.9% for T-ALPPS, respectively. The 1-, 3-, and 5-year DFS for TSH was 66.7%, 9.5%, and 5% vs. 44.6%, 11.1%, and 11.1% for T-ALPPS, respectively. The volume increase with T-ALPPS was superior to that with TSH (68% vs. 39%; P = 0.018). There were no differences in morbidity and mortality after stages 1 and 2. T-ALPPS produces a similar outcome to TSH, indicating that it could be a safe and effective alternative for curative hepatectomy for all patients.

The aim of the study was to identify predictive factors of failure of 2-stage hepatectomy (TSH) for the selection of patients with extensive bilobar colorectal liver metastases (CRLM), who are candidates for TSH.The main weakness of TSH is the risk of failure to complete both the sequential procedures.Between 2000 and 2012, from a total cohort of 845 patients resected for CRLM, 125 patients (14.8%) with extensive CRLM were planned for TSH. All factors related to the failure of TSH were analyzed, and a predictive model was built utilizing the independent predictive factors of failure.Forty-four patients (35.2%) could not proceed to the second stage, and their overall survival (OS) was significantly worse than that of those who completed the TSH (5-year OS: 0% vs 44.2%; P 0.0001). Multivariate analysis revealed that carcinoembryonic antigen30 ng/mL [relative risk (RR) 2.73, P = 0.03], tumor size40 mm (RR 2.89, P = 0.04), chemotherapy cycles12 (RR 3.46, P = 0.01), and tumor progression during first-line chemotherapy (RR 6.56, P = 0.01) were independent predictive factors of failure. For patients not presenting any factors, the probability of failure was 10.5%, with a 5-year OS rate of 41.9%. The addition of each subsequent factor increased the risk to 43.5%, 72.7%, 88.5%, and 95.5%, and decreased the 5-year OS to 38.8%, 29.2%, 0%, and 0%, respectively, for 1, 2, 3, and 4 factors.TSH should not be recommended in patients with more than 2 risk factors. Avoidance of these factors significantly reduces the risk of failure and is crucial for long-term survival.

Two-stage hepatectomy (TSH) with or without portal vein ligation (PVL) or portal vein embolization (PVE) and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) are surgical strategies in the treatment of advanced colorectal liver metastases (CRLM). The role of each strategy is yet ill defined. The aim of this analysis is to share our center experience with conventional TSH with or without PVL/PVE and ALPPS in patients with advanced bilateral CRLM. Data were extracted from a prospectively collected institutional database. Complication rates according to the Dindo-Clavien classification, overall and recurrence-free survival data were analyzed. Between 2008 and 2017, 790 liver resections were performed in 611 patients with CRLM. Out of 320 patients with bilateral disease, TSH (as right or extended right hepatectomy) with or without PVL/PVE was performed in 50 patients and ALPPS in 8. Stage 2 was completed in 36 (72%) out of 50 TSH/PVL/PVE and in all ALPPS patients (100%). Median follow-up was 15.8 months (0.9 to 111.9 months). On an intention-to-treat basis, the median overall survival was 26.7 (21.8–35.1 range) months after TSH/PVL/PVE and 36.2 months (11.3–61.2 range) after ALPPS (p = 0.809). In the TSH/PVL/PVE cohort, the median overall survival was 29.9 (19.0–40.3) months in patients who completed stage 2 compared to 13.8 months in patients who did not (p

Response to "ALPPS Versus Conventional Two-stage Hepatectomy in Patients With Advanced Colorectal Liver Metastases"

This chapter reviews the history, indications, and outcomes of two-stage hepatectomy, including both conventional two-stage resection and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). The underlying mechanisms of liver hypertrophy as they relate to two-stage resection and portal vein occlusion are explored.

Background It is generally accepted that an insufficient future liver remnant is a major limitation of large-scale hepatectomy for patients with primary hepatocellular carcinoma. Conventional two-stage hepatectomy (TSH) is commonly considered to accelerate future liver regeneration despite its low regeneration rate. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which is characterized by a rapid regeneration, has brought new opportunities. Methods Relevant studies were identified by searching the selected databases up to September 2017. Then, a meta-analysis of regeneration efficiency, complication rate, R0 resection ratio, and short-term outcomes was performed. Results Ten studies, comprising 719 patients, were included. The overall analysis showed that ALPPS was associated with a larger hyperplastic volume and a shorter time interval (P

Background Despite the gradual diffusion of laparoscopic liver resection, the feasibility and results of laparoscopic two-stage hepatectomy (TSH) for bilobar colorectal liver metastases (CRLM) have not been described frequently. This study aimed to evaluate the feasibility, safety and oncological outcomes of laparoscopic TSH for bilobar CRLM. Methods All patients eligible for laparoscopic TSH among those treated for bilobar CRLM from 2000 to 2013 were included. Demographics, tumour characteristics, surgical procedures, and short- and long-term outcomes were analysed. Results Laparoscopic TSH was planned in 34 patients with bilobar CRLM, representing 17·2 per cent of all 198 patients treated for bilobar CRLM. Thirty patients received preoperative chemotherapy, and 20 had portal vein occlusion to increase the volume of the remnant liver. Laparoscopic resection of the primary colorectal tumour was integrated within the first-stage hepatectomy in 11 patients. After a median interval of 3·1 months, 26 patients subsequently had a successful laparoscopic second-stage hepatectomy, including 18 laparoscopic right or extended right hepatectomies. The mortality rate for both stages was 3 per cent (1 of 34), and the overall morbidity rate for the first and second stages was 50 per cent (17 of 34) and 54 per cent (14 of 26) respectively. Mean length of hospital stay was 6·1 and 9·0 days respectively. With a median follow-up of 37·8 (range 6–129) months, 3- and 5-year overall survival rates in patients who completed TSH were 78 and 41 per cent respectively. The 3- and 5-year disease-free survival rates were 26 and 13 per cent respectively. Conclusion Laparoscopic TSH for bilobar CRLM is safe and does not jeopardize long-term outcomes in selected patients.

Post hepatectomy liver failure (PHLF) remains a significant cause of morbidity and mortality after major liver resection. Although the etiology of PHLF is multifactorial, an inadequate functional liver remnant (FLR) is felt to be the most important modifiable predictor of PHLF. Pre-operative evaluation of FLR function and volume is of paramount importance before proceeding with any major liver resection. Patients with inadequate or borderline FLR volume must be considered for volume optimization strategies such as portal vein embolization (PVE), two stage hepatectomy with portal vein ligation (PVL), Yttrium-90 radioembolization, and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). This paper provides an overview of assessing FLR volume and function, and discusses indications and outcomes of commonly used volume optimization strategies.

Monosegment 4±1 Associating Liver Partition and Portal Vein ligation for Staged hepatectomy (ALPPS) for bilateral colorectal liver metastases decreases the risk of drop-out of two stage hepatectomy, triggering a rapid and significant increase in future liver remnant (FLR) with promising oncological outcomes. We report two cases of segment 4+1 monosegment ALPPS for multiple colorectal liver metastases performed at our institution. In the literature, seven similar cases have been reported. Short and long term outcomes of our two patients were reported along with a review of data from the literature. Our patients showed a FLR increase from 13% to 37% and from 14% to 41% of total liver volume, respectively. This was compared to a median growth from 19% at baseline to 34% before stage 2, in the literature. After 20 and 27 months since resection both patients are alive and disease-free. In the literature, median overall survival and disease free survival were 13 months (range, 5-24 months) and 5 months (range, 3-23 months), respectively. Segment 4±1 ALPPS is associated with promising oncological outcomes and a significant FLR growth. It may be safely performed in selected patients as a salvage procedure, reducing the risk of the dropout of two-stage hepatectomy.

Background This report describes the technical aspects and outcomes of a laparoscopic approach in planned two-stage liver resections for patients with bilobar colorectal cancer (CRC) liver-only metastases. Methods This is a retrospective review of our database examining consecutive patients who underwent an initial first-stage laparoscopic liver resection for CRC metastases, with a planned second-stage resection from 2007 to 2013. Results Seven patients underwent an initial laparoscopic first stage with concurrent right portal vein ligation (RPVL) in two patients. Median operating time was 100 (60–170) min with a median blood loss of 100 (50–400) mL. Median length of stay was 3 (2–5) days. The remaining five patients required post-operative right portal vein embolization (RPVE). All patients had significant hypertrophy of the future liver remnant (FLR) (future liver remnant volume (FLRV) >25%) and six patients subsequently had a successful open right hepatectomy with one attempted laparoscopically converted to open. Two patients had prolonged bile leaks after the second procedure. Three patients remained disease free, with median follow-up of 34 (13–80) months. One patient had disease progression following RPVE precluding performance of second stage. Conclusion Laparoscopic first-stage resection of tumours in the left liver can be safely combined with RPVL/RPVE to achieve adequate hypertrophy of the FLR, allowing subsequent right hepatectomy.

Liver resection is recognized as the preferred treatment for patients with colorectal liver metastases (CLM) because it offers long-term survival; it is the only hope for a cure. However, in the majority of cases, liver surgery is contraindicated due to the small volume of the future remnant liver. To extend the surgical indications for CLM, a planned two-stage hepatectomy procedure with portal vein embolization (PVE) was developed specifically for patients with multiple and bilobar CLM. The rationale for performing the procedure was a concern about the possible overgrowth of intrafuture remnant liver lesions following PVE, and it was therefore recommended for all multiple bilobar CLM cases, even when one-stage hepatectomy was technically feasible. We recently performed Hobson's choice two-stage hepatectomy in two cases for reasons different from those of the original planned two-stage hepatectomy. In the present report, we describe our Hobson's choice two-stage hepatectomy strategy, which provided favorable short-term outcomes.

Colorectal cancer is the third most common type of cancer in Western countries. In 2012 alone, an estimated 23 300 Canadians received a diagnosis of colorectal cancer and 9200 died from it.[1][1] Of the patients who receive a diagnosis, about one-third will have metastasis confined to the liver,[2][

Background: The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been proposed to avoid liver failure after major liver resection. We thought to define the mechanism by which ALPPS enlarges liver remnant and if it is really more effective than classic two-stage hepatectomy. Objectives: To compare if ALPPS is superior to portal vein ligation (PVL) to increase liver volume. Methods: Sprague-Dawley rats were divided in sham, ALPPS and PVL groups. Animal weight, volumetric assessment of the liver middle lobe, mitotic index, binucleate cells index, Ki-67 index and histological evaluation were done to assess liver regeneration. Results: No differences were found in liver volume after both procedures. (48, 65 ± 15 %, 43, 97 ± 13, 4 % and 155 ± 40 %; on 3, 7, 14 POD, for ALPPS and PVL) The liver volume/ animal weight ratios were similar in both groups. Ki67, binucleate cells and mitotic index were significantly higher in PVL and ALPPS compared with sham group, only on 3 postoperative day, (p=0.01), but were not different at the end of follow up (14 days). The histological liver damage score was slightly higher in ALPPS. Conclusion: Both procedures are useful to achieve increases in future remnant liver volume. There is no difference in the final volume reached; observing that the increase achieved by ALPPS is faster. Fil: Barros Schelotto, Pablo. Fundación Favaloro; Argentina Fil: Moulin, Luis. Fundación Favaloro; Argentina Fil: Meier, Dominik. Universidad Favaloro; Argentina Fil: Almau Trenau, Hector. Fundación Favaloro; Argentina Fil: Cabanne, Ana. Fundación Favaloro; Argentina Fil: Descalzi, Valeria. Fundación Favaloro; Argentina Fil: Stringa, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina. Universidad Favaloro; Argentina Fil: Gondolesi, Gabriel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina. Fundación Favaloro; Argentina

IntroductionSurgical resection offers the best chance of cure for patients with colorectal liver metastases (CRLMs). Two-stage hepatectomy (TSH) has been demonstrated to be safe and effective to obtain curative resection in patients with multiple, bilobar CRLMs that are unresectable in a single procedure. Up to now TSH has been the prerogative of dedicated liver surgery centers. The aim of this study was to assess the safety and effectiveness of TSH also in community hospitals.MethodsOf 294 patients operated on for CRLMs between September 1997 and June 2012 in 2 district community hospitals (belonging to the same regional healthcare district), 43 (14.6%) were scheduled for TSH. Thirty-eight/43 received neoadjuvant and/or bridge chemotherapy (2 neoadjuvant only, 4 neoadjuvant and bridge, 32 bridge only).ResultsThe mean follow-up was 35.74 ± 29.53 months. Five-year overall survival (OS) was 31.4%, with a median survival time of 31 months. Twenty-nine patients completed the planned procedure (OS: 42.9%; median 47 months), while 14 did not because of disease progression (OS: 0%; median 13 months). No operative mortality occurred within the first 90 days either after the first or second stage.ConclusionsOur results suggest good efficacy and safety of TSH even when performed in a community hospital setting. Shifting patient selection from neoadjuvant to bridge chemotherapy had no impact on outcome once the clearing of the liver had been achieved. In patients presenting with synchronous CRLMs, simultaneous colorectal resection and clearing of the less involved hemiliver as the first surgical step is feasible without any negative impact on outcome.

Introduction To report our experience on associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in patients with liver tumors. Methods ALPPS is a surgical technique that allows hepatic resection after rapid liver hypertrophy. Results Thirteen operations were performed: 8 for hepatocellular carcinoma (HCC) with liver cirrhosis (LC) and 5 for colorectal liver metastases (CRLM, n = 3) and cholangiocarcinoma (CC, n = 2) in normal livers (NL). Of the 11 men (85%), the median age was 60 years (range 36–74). Six (75%) HCC patients had BCLC stage C and 2 (25%) had BCLC stage B disease. The median % future liver remnant (FLR) volume increase was 71.7% in patients with LC and 64.8% in NL (p = 0.44). Twelve patients achieved a sufficient FLR growth after the first stage (92.3% efficacy). Four right trisectorectomies and 9 right hepatectomies were performed. All patients completed the second stage (100% feasibility). R0 resection was achieved in all cases. The 90-day mortality rate was 23.1% (12.5% for HCC patients with LC vs 40% for CRLM and CC patients with NL, p = 0.13). After the first stage the overall morbidity rates were 62.5% and 80% (p = 0.61), whereas after the second stage they were 87.5% and 80% in patients with LC and NL respectively (p = 0.99). At a median follow-up of 15 months (range 1–27), the median DFS was 9 months (CI95% 6–12), and the 1yr-DFS was 42%. The median survival was 25 months (CI95% 10–40), and the 1-yr overall survival was 74%. Conclusions ALPPS induced a considerable and comparable FLR growth in HCC patients with liver cirrhosis and patients with CRLM and CC with normal liver parenchyma. HCC patients who underwent ALPPS had a high rate of macrovascular tumor involvement. A high rate of R0 resection is expected in properly selected patients.

The role of laparoscopy in two-stage hepatectomy for bilobar colorectal liver metastases (CRLMs) has not yet been extensively investigated.We reviewed a prospectively collected database of 302 consecutive patients undergoing laparoscopic liver resection at our institution between 2003 and 2011.Eight patients undergoing laparoscopic first/second-stage hepatectomy for bilobar CRLMs (male/female 6:2; median age, 64 years) were analyzed. The first stage consisted of laparoscopic clearance of the left lobe in all patients with no postoperative morbidity and mortality. Seven patients underwent portal vein embolization or ligation. The median interval between first- and second-stage hepatic resections was 89 days (range, 36-123 days). Second-stage hepatectomy with right lobar clearance (open, n=5; laparoscopic, n=2; laparoscopic to open, n=1) was associated with no mortality and an operative morbidity rate of 50%. Adhesions were judged to be minimal or absent during the second-stage procedure. Complications included intra-abdominal collection (n=2), bleeding requiring re-operation (n=1), and bile leak (n=1). R0 resection was obtained in 7 of 8 cases after first-stage resection and in 8 of 8 cases after second-stage resection. Three patients (38%) died from disease recurrence. Of the remaining 5 patients, 4 are disease-free at a median follow-up of 24 months (range, 9-27 months).The well-recognized advantages of laparoscopy may play a favorable role in the management of patients with bilobar CRLMs candidate for a two-stage resection. The first-stage laparoscopic clearance of the left lobe could progressively become the "gold standard." Laparoscopic second-stage hepatectomy should be limited to selected cases.

In patients with two-stage hepatectomy (TSH) for multiple bilobar liver metastases from colorectal cancer, few clinical series compare functional remnant hypertrophy of the liver volume between right portal vein ligation (PVL) and embolisation (PVE). Our objective is to analyse the effectiveness of portal vein ligation to achieve hypertrophy of the functional remnant volume (FRV) of the liver and to compare the results with portal vein embolisation in a series of patients with multiple bilobar liver metastases from colorectal carcinoma.Between September 2001 and September 2011 we performed a TSH in 41 patients with multiple bilobar colorectal liver metastases. A right PVL was performed in 23 patients with an insufficient FRV (three patients did not complete the second stage due to tumour progression and were excluded). We prospectively compare these results with the increased remnant volume obtained in 18 patients with right PVE.The median FRV was higher in the patients with PVE, rising from 501 ml (range 309-703) to 636 ml (range 387-649), than those with PVL, rising from 510 ml (range 203-824) to 595 ml (range 313-1213) (p0.05). The median %FRVI was higher in the patients with PVE (median 40%; range 21-65%) than those with PVL (median 30%; range 21-60%) (p0.05).PVL and PVE were effective in all cases for obtaining hypertrophy of the FRV before major liver resection. Right PVE obtains better results and should be used where necessary to achieve a further increase in volume.

Two stage hepatectomy is currently a method of choice for the treatment of multifocal bilobar hepatic lesions, especially in the setting of hepatic metastases of colorectal malignancies. We describe a technique that facilitates second-stage hepatectomy by taping the major vascular structures of the right liver and performing a hanging maneuver during the first stage.At the first-stage hepatectomy, the right hepatic artery and the right portal branch are dissected free and taped with color-coded silicone tapes. A classic hanging maneuver is performed using a silicone loop. These three loops are left in situ until the second-stage hepatectomy.During the second-stage hepatectomy, the presence of the vascular tapes appears a major aid in the subsequent dissection and control of the major vascular structures, and the hanging loop helps parenchymal section and surgeon orientation, without liver mobilization. Six patients underwent this procedure. In one patient a biliary leak developed after the first-stage procedure, and this required reoperation for drainage. Although there is a risk of thrombosis in this setting, there were no vascular complications related to the tape positioning, nor was there any incidence of infection related to the use of the silicone tape.The technique described here has been in regular use in our department since 2009, and in our experience, it may facilitate second-stage hepatectomy.

Two-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal liver metastases (CLM), but 25-35% of patients fail to complete the scheduled procedure (drop-out). To elucidate if drop-out of TSH is a patient selection (as usually considered) or a loss of chance.All the consecutive patients scheduled for a TSH at the Paul Brousse Hospital between 2000 and 2012 were considered. TSH patients were matched 1:1 with patients receiving a one-stage ultrasound-guided hepatectomy (OSH) at the Humanitas Research Hospital in the same period. Matching criteria were: primary tumor N status; timing of CLM diagnosis; CLM number and distribution into the liver.Sixty-three pairs of patients were analyzed. Demographic and tumor characteristics were similar (median 7 CLM), except for more chemotherapy lines and adjuvant chemotherapy in TSH. Drop-out rate of TSH was 38.1% (0% of OSH). The two groups had similar R0 resection rate (19.0% OSH vs. 15.9% TSH). OSH and completed TSH had similar five-year survival (from CLM diagnosis 49.8% vs. 49.7%, from liver resection 36.1% vs. 44.3%), superior to drop-out (10% three-year survival, p 0.001). OSH and completed TSH had similar recurrence-free survival (at three years 21.7% vs. 20.5%) and recurrence sites. The completion of resection (drop-out vs. OSH/completed TSH) was the only independent prognostic factor (p = 0.003).Drop-out of TSH could be a loss of chance rather than a criteria for patient selection. "Unselected" OSH patients had the same outcomes of selected patients who completed TSH. A complete resection is the main determinant of prognosis.