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

BACKGROUND AND AIMS: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate. METHODS: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis. RESULTS: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P ˂0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively). CONCLUSIONS: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.

Early laparoscopic cholecystectomy in acute mild gallstone pancreatitis. Is there a role for routine admission contrast-enhanced CT Scan?

PURPOSE: This study aims to evaluate the efficacy of admission contrast-enhanced CT scans in formulating strategies for performing early laparoscopic cholecystectomy in cases of acute gallstone pancreatitis. METHODS: Patients diagnosed with acute gallstone pancreatitis underwent a CT scan upon admission (after at least 24 h from symptom onset) to confirm diagnosis and assess peripancreatic fluid, collections, gallstones, and common bile duct stones. Patients with mild acute gallstone pancreatitis, following the Atlanta classification and Baltazar score A or B, were identified as candidates for early cholecystectomy (within 72 h of admission). RESULTS: Within the analyzed period, 272 patients were diagnosed with mild acute gallstone pancreatitis according to the Atlanta Guidelines. A total of 33 patients (12.1%) were excluded: 17 (6.25%) due to SIRS, 10 (3.6%) due to local complications identified in CT (Balthazar D/E), and 6 (2.2%) due to severe comorbidities. Enhanced CT scans accurately detected gallstones, common bile duct stones, pancreatic enlargement, inflammation, pancreatic collections, and peripancreatic fluid. Among the cohort, 239 patients were selected for early laparoscopic cholecystectomy. Routine intraoperative cholangiogram was conducted in all cases, and where choledocholithiasis was present, successful treatment occurred through common bile duct exploration. Only one case required conversion from laparoscopic to open surgery. There were no observed severe complications or mortality. CONCLUSION: Admission CT scans are instrumental in identifying clinically stable patients with local tomographic complications that contraindicate early surgery. Patients meeting the criteria for mild acute gallstone pancreatitis, as per Atlanta guidelines, without SIRS or local complications (Baltazar D/E), can safely undergo early cholecystectomy within the initial 72 h of admission.

Fascial dehiscence: predictable complication? Development and validation of a risk model: a retrospective cohort study.

PURPOSE: Fascial dehiscence is still an important cause of morbidity and mortality in the postoperative period of abdominal surgery. Different authors have sought to identify risk factors for this entity. Two risk scores have been developed, but they include postoperative variables, which hinder preventive decision-making during the early surgical period. Our aim is to identify preoperative and intraoperative risk factors for fascial dehiscence and to develop and validate a risk prediction score that allows taking preventive behaviors. METHODS: All adult patients, with no prior history of abdominal surgery, who underwent midline laparotomy by a general surgery division between January 2009 and December 2019 were included. Recognized preoperative risk factors for fascial dehiscence were evaluated in a univariate analysis and subsequently entered in a multivariate stepwise logistic regression model. A prognostic risk model was developed and posteriorly validated by bootstrapping. This study was conducted following the STROBE statement. RESULTS: A total of 594 patients were included. Fascial dehiscence was detected in 41 patients (6.9%). On multivariate analysis, eight factors were identified: chronic obstructive pulmonary disease (COPD), immunosuppression, smoking, prostatic hyperplasia, anticoagulation use, sepsis, and overweight. The resulting score ranges from 1 to 8. Scores above 3 are predictive of 18% risk of dehiscence with a sensitivity of 70% and specificity of 80% (ROC 0.88). CONCLUSIONS: We present a new preoperative prognostic score to identify patients with a high risk of fascial dehiscence. It can be a guide for decision-making that allows taking intraoperative preventive measures. External validation is still required.

Surgical strategies to treat portal vein thrombosis during adult liver transplantation.

BACKGROUND: The incidence of portal vein thrombosis (PVT) at the time of liver transplantation (LT) may be variable and underestimated. Therefore, preoperative diagnosis and stratification of its extension is so relevant for adequate surgical planning. Revascularization of the portal vein graft becomes essential for graft and patient survival after LT. Early stages of PVT may be managed with eversion thrombectomy and end-to-end anastomoses. However, severe PVT (grades 3 and 4) poses significant challenges for patients requiring LT, resulting in more complex surgeries and higher complication rates. To address these complexities, various surgical techniques have been developed, including collateral alternative vessel utilization, renoportal anastomoses, mesoportal jump graft placement, cavoportal hemitranspositions, portal vein arterialization, or even multivisceral transplantation. PURPOSE: We herein describe the preoperative surgical planning as well as the different surgical strategies possible to treat portal vein thrombosis during LT. CONCLUSION: A comprehensive preoperative evaluation of PVT is crucial for accurately assessing its extent and severity. This information is vital for proper surgical planning, which ultimately prepares both the surgeon and the patient for potentially complex procedures during LT. The surgical alternatives presented in this technical report offer promising solutions for treating PVT during LT, making it a viable option for selected patients.

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

AIM: To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies. BACKGROUND: Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown. METHODS: Data from consecutive hepatectomy patients (55 females, 67 males) and from the international ALPPS (Associating-Liver-Partition-and-Portal-vein-ligation-for-Staged-hepatectomy, a two stage hepatectomy) registry (449 females, 729 males) were analyzed. Endpoints were severe morbidity (≥3b Clavien-Dindo grades), Model for End-stage Liver Disease (MELD) scores, and ALPPS interstage intervals. For validation and mechanistic insight, female-male ALPSS mouse models were established. t , χ 2 , or Mann-Whitney tests were used for comparisons. Univariate/multivariate analyses were performed with sensitivity inclusion. RESULTS: Following major hepatectomy (Hx), males had more severe complications ( P =0.03) and higher liver dysfunction (MELD) P =0.0001) than females. Multivariate analysis established male sex as a predictor of complications after ALPPS stage 1 (odds ratio=1.78; 95% confidence interval: 1.126-2.89; P =0.01), and of enhanced liver dysfunction after stage 2 (odds ratio=1.93; 95% confidence interval: 1.01-3.69; P =0.045). Female patients displayed shorter interstage intervals (<2 weeks, 64% females versus 56% males, P =0.01), however, not in postmenopausal subgroups. In mice, females regenerated faster than males after ALPPS stage 1, an effect that was lost upon estrogen antagonism. CONCLUSIONS: Poorer outcomes after major surgery in males and shorter ALPPS interstage intervals in females not necessarily suggest a superior regenerative capacity of female liver. The loss of interstage advantages in postmenopausal women and the mouse experiments point to estrogen as the driver behind these sex disparities. Estrogen's benefits call for an assessment in postmenopausal women, and perhaps men, undergoing major liver surgery.

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

BACKGROUND: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR). METHODS: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula. RESULTS: A total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18-0.28) and 0.39 (IQR: 0.31-0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p = .02), height ˃1.76 m (p ˂ .01), weight ˃83 kg (p ˂ .01), BMI˃28 (p ˂ .01), male gender (p ˂ .01), antihypertensive therapy (p ˂ .01), operation time ˃370 minutes (p ˂ .01) and hospital stay˃14 days (p ˂ .01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male. CONCLUSIONS: Height, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.

Impact of resident involvement on patient outcomes in laparoscopic cholecystectomy of different degrees of complexity: analysis of 2331 cases.

BACKGROUND: Resident involvement in the operating room is a vital component of their medical education. Laparoscopic cholecystectomy (LC) represents the paradigmatic minimally invasive training procedure, both due to its prevalence and its different forms of complexity. We aim to evaluate whether the supervised participation of residents as operative surgeons in LC of different degrees of complexity affects postoperative outcomes in a university hospital. METHODS: This is a retrospective, single-center study that included all consecutive adult (> 18 years old) patients operated for a LC between January 1, 2012 and December 31, 2017. Each surgical procedure was recorded according to the level of complexity that we established in three types of categorization (level 1: elective surgery; level 2: cholecystitis; level 3: biliary instrumentation). Patients were clinically monitored at an outpatient clinic 7 and 30-day postoperative. Postoperative outcomes of patients operated by supervised residents (SR) and trained surgeons (TS) were compared. Postoperative complications were graded according to the Clavien-Dindo classification of surgical complications. RESULTS: A total of 2331 patients underwent LC during the study period, of whom 1573 patients (67.5%) were operated by SR and 758 patients (32.5%) by TS. There were no significant differences among age, sex, and BMI between patients operated in both groups, with the exception of ASA (P = 0.0001). Intraoperative cholangiography was performed in 100% of the patients, without bile duct injuries. There were no deaths in the 30 postoperative days. The overall complication rate was 5.70% (133 patients), with no significant differences when comparing LC performed by SR and TS (5.09 vs. 6.99%; P = 0.063). The severity rates of complications were similar in both groups (P = 0.379). Patient readmission showed a statistical difference comparing SR vs TS (0.76% vs. 2.2%; P = 0.010). The postoperative complications rate according to the complexity level of LC was not significant in level 1 and 2 for both groups. However in complexity level 3 the TS group experienced a greater rate of complications compared to the SR group (18.12% vs. 9.38%; P = 0.058). In the multivariate analysis, the participation of the residents as operating surgeons was not independently associated with an increased risk of complications (OR 1.22, 95% CI 0.84-1.77; P = 0.275), neither other risk factors like age ≥ 65 years, BMI, complexity level 2-3, or ASA ≥ 3-4. The association of another surgical procedure with the LC was an independent factor of morbidity (OR 3.85, 95% CI 2.54-5.85; P = 0.000). CONCLUSION: Resident involvement in LC with different degrees of complexity did not affect postoperative outcomes. The participation of a resident as operating surgeon is not an independent risk factor and may be considered ethical, safe, and reliable whenever implemented in the background of a residency-training program with continuous supervision and national accreditation. The sum of other procedures not related to a LC should be taken as a risk factor of morbidity.

Role of laparoscopy in the treatment of internal biliary fistulas in a high-volume center and a review of the literature.

BACKGROUND: Biliary fistulas may result as a complication of gallstone disease. According to their tract, abdominal internal biliary fistulas may be classified into cholecystobiliary and bilioenteric fistulas. Surgical treatment is challenging and requires highly trained surgeons with high preoperative suspicion. Conventional surgery is still of choice by most of the authors. However, laparoscopy is emerging as a minimally invasive alternative. We investigated the surgical approach, conversion rate, and outcomes according to the type of biliary fistula. METHODS: We retrospectively reviewed 11,130 laparoscopic cholecystectomies, 31 open cholecystectomies, and 31 surgeries for gallstone ileus at our institution from May 2007 to May 2020. We diagnosed internal biliary fistula in 73 patients and divided them into two groups according to their fistulous tract: cholecystobiliary fistula and bilioenteric fistula. We described demographic characteristics, preoperative imaging modalities, surgical approach, conversion rates, surgical procedures, and outcomes. We additionally revised the literature and compared our results with 13 studies from the past 10 years. RESULTS: There were 22 and 51 patients in the cholecystobiliary and bilioenteric groups, respectively. Our preoperative suspicion of a fistula was 80%. We started 88% of procedures by laparoscopic approach. The effectiveness of laparoscopy in the resolution of internal biliary fistula was 40% for cholecystobiliary fistula and 55% for bilioenteric fistulas. The most frequent cause for conversion to laparotomy was the difficulty to identify anatomical features, in addition to the need to perform a Roux en-Y hepaticojejunostomy. Choledocholithiasis was not associated with an increase in conversion rates. CONCLUSIONS: Laparoscopic resolution of a biliary fistula is still a matter of controversy. Despite the high conversion rates, we believe that a great number of patients benefit from this minimally invasive technique. A high preoperative suspicion and trained surgeons are vital in the treatment of internal biliary fistulas.

Laparoscopic vs open liver resection for metastatic colorectal cancer: analysis of surgical margin status and survival.

BACKGROUND: Liver resection represents the curative treatment of choice for patients with colorectal liver metastases (CRLM). Laparoscopic hepatectomy in CRLM is considered a safe approach. However, the information on their oncological results in the different series is deficient. This study aimed to compare the surgical margin, overall survival (OS), and disease-free survival (DFS) in patients with oncological resections of CRLM according to the type of surgical approach performed. METHODS: Between April 2007 and June 2017, 263 patients with CRLM underwent hepatic resection. Inclusion criteria were initial resectability, tumor size ≤ 50 mm, 3 or less metastases, no bilobar involvement, and absence of extrahepatic disease. A propensity score was performed to adjust the indication bias. RESULTS: Eighty-two patients were included (56 open and 26 laparoscopic). Twenty-eight (50%) patients had synchronous presentation in the open approach and 6 (23%) in the laparoscopic approach (p = 0.021), with more frequent simultaneous open resections (p = 0.037). The resection margin was positive (R1) in 5 patients with an open approach and 2 with a laparoscopic approach (8.9% and 7.6% respectively; p = 0.852). Nine patients (16%) with conventional approach and 2 (7.7%) with laparoscopic approach had local complications (p = 0.3). There was one death in the open group and none in the laparoscopic. There were no significant differences in OS and DFS rate between both groups (1-3 years, OS: 92-77% and 96-75% respectively; 1-3 years, DFS: 63-20% and 73-36% respectively). CONCLUSIONS: There were no significant differences in terms of surgical margin, OS rate, and DFS rate between the laparoscopic and open approach in patients with CRLM.

Long-term follow-up of Branch-Duct Intraductal Papillary Mucinous Neoplasms with negative Sendai Criteria: the therapeutic challenge of patients who convert to positive Sendai Criteria.

BACKGROUND: The management of Branch-Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN) is still controversial. Our objective was to assess the long-term follow-up (FU) of patients with "low-risk" BD-IPMN according to the Sendai-International Consensus Guidelines (ICG-I). METHODS: We retrospectively analyzed a cohort of patients with BD-IPMN and Negative Sendai-Criteria (NSC) from January 2004 to October 2019. A univariate analysis was performed to determine factors associated with conversion to Positive Sendai-Criteria (PSC) and malignancy. Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the IGC-I were assessed for the development of malignancy. RESULTS: A total of 219 patients were selected and underwent a median 58-month FU. Thirty-seven (17%) patients developed PSC during FU including 12 (5.5%) with malignant lesions. Conversely, 182 patients (83%) did not develop malignancy. The NPV and PPV of ICG-I for malignancy were 100% and 32.4%, respectively. Among patients who developed PSC, those with cancer were >65years (OR = 3.57;p = 0.015) and had significantly higher serum CA-19-9 levels (OR = 5.27;p = 0.007). CONCLUSION: The ICG-I is a safe strategy for FU of patients with BD-IPMN. The absence of PSC exclude malignancy. Among patients who develops PSC, the risk of cancer remains low and surgery should be decided according to their surgical risk and life expectancy.

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

BACKGROUND: Repeated liver resections for the recurrence of colorectal liver metastasis (CRLM) are described as safe and have similar oncological outcomes compared to first hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is performed in patients with conventionally non-resectable CRLM. Repeated resections after ALPPS has not yet been described. METHODS: Patients that underwent repeated liver resection in recurrence of CRLM after ALPPS were included in this study. The primary endpoint was morbidity and secondary endpoints were mortality, resection margin and survival. RESULTS: Thirty patients were included in this study. During ALPPS, most of the patients had classical split (60%, n = 18) and clearance of the FLR (77%, n = 23). Hepatic recurrence was treated with non-anatomical resection (57%, n = 17), resection combined with local ablation (13%, n = 4), open ablation (13%, n = 4), segmentectomy (10%, n = 3) or subtotal segmentectomy (7%, n = 2). Six patients (20%) developed complications (10% minor complications). No post-hepatectomy liver failure or perioperative mortality was observed. One-year patient survival was 87%. Five patients received a third hepatectomy. CONCLUSION: Repeated resections after ALPPS for CRLM in selected patients are safe and feasible with low morbidity and no mortality. Survival seems to be comparable with repeated resections after conventional hepatectomy.

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

BACKGROUND: Various, often conflicting, estimates for post-operative morbidity and mortality following ALPPS have been reported in the literature, suggesting that considerable center-level variation exists. Some of this variation may be related to center volume and experience. METHODS: Using data from seventeen centers who were early adopters of the ALPPS technique, we estimated the variation, by center, in standardized 90-day mortality and comprehensive complication index (CCI) for patients treated between 2012 and 2018. RESULTS: We estimated that center-specific 90-day mortality following treatment with ALPPS varied from 4.2% (95% CI: 0.8, 9.9) to 29.1% (95% CI: 13.9, 50.9), and that center-specific CCI following treatment with ALPPS varied from 17.0 (95% CI: 7.5, 26.5) to 49.8 (95% CI: 38.1, 61.8). Declines in estimated 90-day mortality and CCI were observed over time, and almost all individual centers followed this trend. Patients treated at centers with a higher number of ALPPS cases performed over the prior year had a lower risk of post-operative mortality. CONCLUSION: Despite considerable center-level variation in ALPPS outcomes, perioperative outcomes following ALPPS have improved over time and treatment at higher volume centers results in a lower risk of 90-day mortality. Morbidity and mortality remain concerningly high at some centers.

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

OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Liver transplantation for non-resectable colorectal liver metastasis: where we are and where we are going.

PURPOSE: Almost 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastasis (LM). Although their only long-term curative treatment is surgery, less than half of these patients can be eventually resected. Therefore, palliative chemotherapy is offered as a definitive option, though with poor results. Recently, the University of Oslo group has published encouraging results in the treatment of these patients with liver transplantation (LT), whereby worldwide interest in this option has been renewed. METHODS: A literature review of LT for patients with unresectable colorectal metastasis was performed. This included information regarding patient selection, complications, overall survival (OS) and disease-free survival (DFS), immunosuppression, chemotherapy, and description of the ongoing trials. RESULTS: Improvements in OS and DFS have been observed in consecutive published prospective trials, as patient selection has been refined. Papers reporting OS of patients who randomly presented similar selection criteria also exhibited good results. CONCLUSION: LT within the available therapeutic options in patients with CRC-LM seems to be a compelling alternative in carefully selected patients. The ongoing trials will provide valuable information regarding selection criteria, immunosuppressive therapy and different modalities of adjuvant chemotherapy, which are, to our knowledge, the vital platform of LT in CRC-LM. Although some of the developing techniques involve living donors, graft availability for these patients remains a matter of major concern.

ALPPS in neuroendocrine liver metastases not amenable for conventional resection - lessons learned from an interim analysis of the International ALPPS Registry.

BACKGROUND: Surgery is the most effective treatment option for neuroendocrine liver metastases (NELM). This study investigated the role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a novel strategy in treatment of NELM. METHODS: The International ALPPS Registry was reviewed to study patients who underwent ALPPS for NELM. RESULTS: From 2010 to 2017, 954 ALPPS procedures from 135 international centers were recorded in the International ALPPS Registry. Of them, 24 (2.5%) were performed for NELM. Twenty-one patients entered the final analysis. Overall grade ≥3b morbidity was 9% after stage 1 and 27% after stage 2. Ninety-day mortality was 5%. R0 resection was achieved in 19 cases (90%) at stage 2. Median follow-up was 28 (19-48) months. Median disease free survival (DFS) was 17.3 (95% CI: 7.1-27.4) months, 1-year and 2-year DFS was 73.2% and 41.8%, respectively. Median overall survival (OS) was not reached. One-year and 2-year OS was 95.2% and 95.2%, respectively. CONCLUSIONS: ALPPS appears to be a suitable strategy for inclusion in the multimodal armamentarium of well-selected patients with neuroendocrine liver metastases. In light of the morbidity in this initial series and a high rate of disease-recurrence, the procedure should be taken with caution.

Defining Benchmark Outcomes for ALPPS.

OBJECTIVE: 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). BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Biliary reconstruction before clamp removal to avoid portal vein thrombosis in pediatric living-donor liver transplantation using hyper-reduced left lateral segment grafts: A novel technical strategy.

LT has become the treatment of choice for children with end-stage liver disease. The scarcity of donors and the considerable mortality on waiting lists have propelled the related living-donor techniques, especially in small children. This population need smaller and good quality grafts and are usually candidates to receive a LLS from a related donor. Many times this grafts are still large and do not fit in the receptor's abdomen, so a further hyper-reduction may be required. Despite all advances in LT field, vascular complications still occur in a considerable proportion remaining as a significant cause of morbidity, graft loss, and mortality. Technical issues currently play an essential role in its genesis. The widely spread technique for biliary and vascular reconstruction in living donor LT (LDLT) nowadays implies removal of the portal vein (PV) clamp after the venous anastomosis, then the arterial reconstruction is done, followed by the biliary reconstruction. However, due to the posterior location of the LLS bile duct, for its reconstruction, a rotation of the liver is required risking a potential transient PV occlusion leading to thrombosis afterward. We describe a new technique that involves performing biliary reconstruction after the PV anastomosis and before removing the vascular clamp, thus allowing to freely rotate the liver with less risk of PV occlusion and thrombosis.

Prognostic impact of K-RAS mutational status and primary tumor location in patients undergoing resection for colorectal cancer liver metastases: an update.

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10-1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1-R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.

Interstage Assessment of Remnant Liver Function in ALPPS Using Hepatobiliary Scintigraphy: Prediction of Posthepatectomy Liver Failure and Introduction of the HIBA Index.

OBJECTIVE: The aim of this study was to evaluate interstage liver function in associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) using hepatobiliary scintigraphy (HBS) and whether this may help to predict posthepatectomy liver failure (PHLF). BACKGROUND: ALPPS remains controversial given the high rate of liver-related mortality after stage 2. HBS combined with single photon emission computed tomography (SPECT) accurately estimates future liver remnant function and may be useful to predict PHLF. METHODS: Between 2011 and 2016, 20 of 39 patients (51.3%) underwent SPECT-HBS before ALPPS stage 2 for primary (n = 3) or secondary liver tumors (n = 17) at the Hospital Italiano de Buenos Aires (HIBA). PHLF was defined by the International Study Group of Liver Surgery criteria, 50-50 criteria, or peak bilirubin >7 mg/dL. Grade A PHLF was excluded, as it requires no change in clinical management. Receiver-operating characteristic curves were used to determine cutoff for HBS parameters. RESULTS: Interstagely, 3 HBS parameters differed significantly between patients with (n = 4) and without PHLF (n = 16) after stage 2. Among these, the HIBA-index best predicted PHLF, with a cutoff value of 15%. The risk of PHLF in patients with cutoff <15% was 80%, whereas no patient with cutoff ≥15% developed PHLF. CONCLUSIONS: Interstage HBS could help to predict clinically significant PHLF after ALPPS stage 2. An HIBA-index cutoff of 15% seemed to give the best diagnostic performance. Although further studies are needed to confirm our findings, the routine application of this noninvasive low-cost examination could facilitate decision-making in institutions performing ALPPS.