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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. 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. 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. 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.

The surgical strategy to resolve the underlying biliary pathology in patients with acute gallstone pancreatitis (AGP) remains controversial. The aim of this study was to evaluate the safety and effectiveness of early laparoscopic cholecystectomy (ELC) in patients with mild AGP. A retrospective cohort of consecutive patients diagnosed with mild AGP according to the Atlanta Guidelines from January 2009 to July 2019 was selected. Patients were assigned to surgery on the first available surgical shift, 48 h after the symptoms onset. Univariate analysis was performed to determine the association between AGP and grades of Balthazar (A, B and C) with time to surgery, days of hospitalization and postoperative complications. From 239 patients evaluated, 238 (99.58%) were operated by laparoscopic approach. Intraoperative cholangiogram was performed routinely. Choledocholithiasis, if present, was successfully treated by laparoscopic common bile duct exploration in all cases. A significant association was found between Balthazar grades and time to surgery (median of 3 days, p = 0.003), with length hospitalization and from surgery to discharge, with median of 4 days (p = 0.0001) and 2 days (p = 0.003), respectively. Mild postoperative complications (CD I/II) were observed in 22/239 patients (9.2%). This represents 2% of patients with grade A of Balthazar, 9% of grade B and 14% of grade C (p = 0.016). We observed no severe complications or mortality. ELC with routine intraoperative cholangiogram, performed on the first available surgical shift 48 h after the symptoms of pancreatitis onset, is a viable, effective and safe strategy for the resolution of mild AGP and its underlying biliary pathology in a single procedure.

BACKGROUND Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications CASE SUMMARY A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up. CONCLUSION HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.

To evaluate short- and long-term outcomes after live-donor liver transplantation (LT) with hyper-reduced grafts in low-weight pediatric recipients. LT is an established curative therapy for children with end-stage chronic liver disease or acute liver failure. A major problem in pediatric LT has been the lack of size-matched donor organs. The disadvantage of the use of large-for-size grafts is the insufficient tissue oxygenation and graft compression, which result in poor outcomes. The shortage of suitable donors is most notable in children under 10 kg. To overcome such obstacle, in situ hyper-reduced live-donor liver grafts have been introduced. Available articles in the literature are based on small samples and are deficient in long-term follow-up. A single-cohort, retrospective analysis was conducted including 59 pediatric patients under 10 kg who underwent hyper-reduced (in situ “a la carte” left lateral segment reduction) live-donor LT (LDLT) between February 1994 and February 2018. The most frequent cause of liver failure was biliary atresia (70%). Median recipient weight was 8 kg. Vascular complications were confirmed in 15% of the sample, while 45% presented biliary complications. Median follow-up time was 40.3 months. Ten-year overall survival rate was 74%. Pediatric end-stage liver disease score > 23 was associated with a higher risk of post-operative complications. LDLT can be undertaken in children with body weight

Factor XI (FXI) deficiency is a rare congenital hemostatic disorder associated with increased bleeding tendency in trauma, surgery or when other hemostatic defects are present. Perioperative hemostatic management of a patient with a severe FXI deficiency undergoing major oncological liver and colorectal surgery with therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) is reported.A 54-year-old male with severe FXI deficiency was scheduled for resection of synchronous rectal cancer and multiple liver metastases. Baseline prothrombin time (PT) was 97 %, activated partial thromboplastin time (aPTT) 89 s(s) and FXI levels1 IU/dL. The rotational thromboelastometry (ROTEM™) presented a prolonged INTEM clotting time (CT) = 443 s (RV 100-240 s) and a clot formation time (CFT) = 110 s (RV 30-100 s). TPE with FFP was carried out achieving FXI levels up to 46 IU/dL and an aPTT of 33 s, normalizing thromboelastometry parameters to an INTEM CT = 152 s and a CFT = 86 s before the procedure. After surgery, the patient received daily FFP to maintain FXI levels above 30 IU/dL until discharge on the eighth day. A total of 30 FFP units were transfused during hospital stay. No significant bleeding events neither transfusion related complications were observed during the perioperative period.Given the lack of correlation between FXI levels and bleeding risk, a multidisciplinary approach based on daily FXI levels monitoring, close clinical assessment and factor supplementation is mandatory. In conclusion, TPE with FFP is an efficacious alternative strategy to correct severe FXI deficiency in patients undergoing major surgery.

Introduction Two novel clinical risk scores (CRS) that incorporate KRAS mutation status (modified CRS (mCRS) and GAME score) were developed. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS. Methods Patients undergoing hepatectomy for CRLM (2000-2018) in ten centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrel's C-index and Akaike's Information Criterion. Results In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14405, 14447, and 14319, respectively. Conclusion In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS.

Acute biliary pancreatitis (ABP) is often associated with persistent common bile duct (CBD) stones. The best strategy in terms of timing of surgery is still controversial. The aim of the current study is to describe the prevalence of persistent common bile duct (CBD) stones in ABP during the first week of symptoms at a high-volume referral center. Single-institution retrospective analysis of a prospectively collected database. Patients with diagnosis of ABP who underwent laparoscopic cholecystectomy (LC) between January 2009 and December 2019 were extracted. Two hundred thirty-one patients were included. Cholecystectomy was performed laparoscopically in 230 (99.57%) patients. Intraoperative cholangiogram was performed in all patients. Two hundred nine (90%) patients had surgery within the first 7 days. Global prevalence of persistent CBD stones during IOC was 19.91% (95% CI 14.96–25.65). No significant association between timing to surgery and presence of CBD stones was found for the first week since the initial attack (p=0.28). Prevalence of CBD stones was significantly higher after day 7 (p=0.007 and 0.005). Positive findings in preoperative MRCP are significantly related to intraoperative CBD stones (p=0.0001). Mild postoperative complications (CD I/II) were present in 21 patients (9.09%). No difference was found in morbidity between CBD stones group and non-CBD stones group (p=0.48). We observed no severe complications nor mortality. In patients with mild acute biliary pancreatitis, the prevalence of persistent CBD stones does not change within the first 7 days since the onset of symptoms. This fact may have major clinical relevance when deciding the optimal therapeutic strategy in this population.

Background Liver transplantation (LT) has been used as a last resort in patients with end-stage liver disease due to bile duct injuries (BDI) following cholecystectomy. Our study aimed to identify and evaluate factors that cause or contribute to an extended liver disease that requires LT as ultimate solution, after BDI during cholecystectomy. Methods Data from 8 high-volume LT centers relating to patients who underwent LT after suffering BDI during cholecystectomy were prospectively collected and retrospectively analyzed. Results Thirty-four patients (16 men, 18 women) with a median age of 45 (range 22-69) years were included in this study. Thirty of them (88.2%) underwent LT because of liver failure, most commonly as a result of secondary biliary cirrhosis. The median time interval between BDI and LT was 63 (range 0-336) months. There were 23 cases (67.6%) of postoperative morbidity, 6 cases (17.6%) of post-transplant 30-day mortality, and 10 deaths (29.4%) in total after LT. There was a higher probability that patients with concomitant vascular injury (hazard ratio 10.69, P=0.039) would be referred sooner for LT. Overall survival following LT at 1, 3, 5 and 10 years was 82.4%, 76.5%, 73.5% and 70.6%, respectively. Conclusion LT for selected patients with otherwise unmanageable BDI following cholecystectomy yields acceptable long-term outcomes. CA extern

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach emerged as a promising surgical strategy for rapid and large hypertrophy of the future liver remnant (FLR) when a major liver resection is necessary. Colorectal liver metastasis (CRLM) is their main indication. However, the promising results published so far, are very difficult to interpret since they usually focus on the technique and not on the underlying disease. Moreover, they are usually made up of complex populations, which received different chemotherapy schemes, with the ALPPS technical variations implemented over time and without consistent long-term follow-up results as well. Whereby, its role in CRLM should be analyzed as carefully as possible to indicate and select the best candidates who will benefit the most from this approach. We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to the ALPPS and CRLM.

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. 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. 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. 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.

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.

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.

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.

Annals of surgical oncology (2020). doi:10.1245/s10434-019-08192-z, Published by Springer, Berlin [u.a.]

Purpose Pancreatic cancer (PC) has not changed overall survival in recent years despite therapeutic efforts. Surgery with curative intent has shown the best long-term oncological results. However, 80%-85% of patients with these tumors are unresectable at the time of diagnosis. In those patients, first therapeutic attempts are minimally invasive or surgical procedures to alleviate symptoms. The addition of radiotherapy (RT) to standard chemotherapy, ergo chemoradiation, in patients with locally advanced pancreatic cancer (LAPC) is still controversial. The study aims to compare outcomes in patients with a double bypass surgery due to LAPC treated or not with RT. Materials and methods A retrospective cohort study of patients with double bypass for LAPC were registered and divided into two groups: treated or not with postoperative RT. Baseline characteristics, postoperative complications, those related to RT and their relation to the main event (mortality) were compared. Results Seventy-four patients were included. Surgical complications between the groups did not offer significant differences. Complications related to RT were mostly mild, and 86% of patients completed the treatment. Overall survival at 1 and 2 years for patients in the exposed group was 64% and 35% vs. 50% and 28% in the non-exposed group, respectively (p = 0.11; power 72%; hazard ratio = 0.53; 95% confidence interval, 0.24-1.18). Conclusion We observed a tendency for survival improvement in patients with postoperative RT. However, we've not had enough power to demonstrate this difference, possibly due to the small sample size. It is indispensable to develop randomized and prospective trials to guide more specific treatment lines in this patients.

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.

Background Acute calculous cholecystitis (ACC) is the most common complication of cholelithiasis. Laparoscopic cholecystectomy (LC) is the gold standard treatment in mild and moderate forms. Currently there is consensus for the use of antibiotics in the preoperative phase of ACC. However, the need for antibiotic therapy after surgery remains undefined with a low level of scientific evidence. Methods The CHART (Cholecystectomy Antibiotic Randomised Trial) study is a single-center, prospective, double blind, and randomized trial. Patients with mild to moderate ACC operated by LC were randomly assigned to receive antibiotic (amoxicillin/clavulanic acid) or placebo treatment for 5 consecutive days. The primary endpoint was postoperative infectious complications. Secondary endpoints were as follows: (1) duration of hospital stay, (2) readmissions, (3) reintervention, and (4) overall mortality. Results In the per-protocol analysis, 6 of 104 patients (5.8%) in the placebo arm and 6 of 91 patients (6.6%) in the antibiotic arm developed postoperative infectious complications (absolute difference 0.82 (95% confidence interval, −5.96 to 7.61, P = .81). The median hospital stay was 3 days. There was no mortality. There were no differences regarding readmissions and reoperations between the 2 groups. Conclusion Although this trial failed to show noninferiority of postoperative placebo compared to antibiotic treatment after LC for mild and moderate ACC within a noninferiority margin of 5%, the use of antibiotics in the postoperative period does not seem justified, because it was not associated with a decrease in the incidence of infectious and other types of morbidity in the present study.

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 >7mg/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

Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative, 2-staged hepatectomy which has elicited controversy within the international hepatobiliary community. Uptake of ALPPS has been limited due to concerns related to evidence of high morbidity and mortality, and scant oncologic and outcome data on quality of life (Qol). Demonstrating reasonable long-term benefits with a short-term risk is necessary to support more widespread endorsement of ALPPS. Our aim was to describe the intermediate-term survival and patient-reported quality of life outcomes after an ALPPS. Methods Prospectively collected data from 2 high-volume ALPPS centers, who were pioneers with the technique, were combined and analyzed for disease-free and overall survival from date of the ALLPS. Only patients treated for colorectal liver metastases with >6 month postoperative follow-up were included. All patients had bilateral colorectal liver metastases with an initially unresectable tumor load, and received preoperative chemotherapy. Information concerning the demographics of the patients, characteristics of the tumor, and treatment were analyzed. The well-validated European Organization for Research and Treatment for Cancer Quality of Life Core Questionnaire version 3.0 questionnaire was used to assess patient quality of life. Results A total of 58 patients underwent ALPPS for colorectal liver metastases, and 47 patients met our inclusion criteria. There were no perioperative mortalities, and the rate of severe complications was 21%. At 3 years post-ALPPS, the overall survival was 50%, while the disease-free survival was 13%. The commonest site of first recurrence was the liver alone (38%). Patient-reported quality of life after ALPPS was similar to reference values for general population. Conclusion In select patients operated at experienced centers, ALPPS results in low perioperative risk, satisfactory overall survival, and excellent quality of life. Hepatic recurrence and not systemic recurrence is the most common site of relapse after ALPPS.

Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows the resection of colorectal liver metastases with curative intent which would otherwise be unresectable and only eligible for palliative systemic therapy. This study aimed to compare outcomes of ALPPS in patients with otherwise unresectable colorectal liver metastases with matched historic controls treated with palliative systemic treatment. Methods All patients with colorectal liver metastases from the international ALPPS registry were identified and analyzed. Survival data were compared according to the extent of disease. Otherwise unresectable ALPPS patients were defined by at least 2 of the following criteria: ≥6 metastasis, ≥2 future remnant liver metastasis, ≥6 involved segments excluding segment 1. These patients were matched with patients included in 2, phase 3, metastatic, colorectal cancer trials (CAIRO and CAIRO2) using propensity scoring in order to compare survival. Results Of 295 patients with colorectal liver metastases in the ALPPS registry, 70 patients had otherwise unresectable disease defined by the proposed criteria. Two-year overall survival was 49% and 72% for patients with ≥2 and

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

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.

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.

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.

Liver resection combined with colorectal surgery (CRS) is the only curative option in many patients presenting with synchronous colorectal cancer and liver metastases (CRLM). Simultaneous resection has been shown to offer benefits in patients with low hepatic tumor load; however, in the setting of in situ colorectal tumor with extensive CRLM and a small predicted future liver remnant (FLR), the use of simultaneous ALPPS and CRS is controversial, lacking outcome data. Thirty-one cases of simultaneous ALPPS and CRS prospectively entered into the International ALPPS Registry were examined. Univariate analysis was used to identify factors associated with 90-day mortality after stage-2. Thirty patients (97%) completed both stages. CRS was performed during stage-1 in 22 patients (73%). Seven patients (23%) had severe complications (Clavien-Dindo ≥ IIIb) following stage-2 ALPPS. The 90-day mortality rate was 15%. Patients who had a severe complication after stage-1 were significantly more likely to have 90-day mortality following stage-2 (p = 0.002). MELD score > 10 on postoperative day-5 after stage-1 was also significantly associated with 90-day mortality (p = 0.011). Disease-free survival and overall survival were 36% and 76% at 1 year, respectively. In light of the high mortality and poor long-term survival identified in this series, the adoption of ALPPS with CRS cannot be recommended without further data. Patients who suffer severe complications or have an elevated MELD score after stage-1 are at higher risk of mortality following stage-2.

The current associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach is represented by an aggressive first surgical procedure followed by a shorter and less aggressive second procedure. This paradigm has been associated with high morbidity and mortality. Inverting the aggressiveness of the surgical stages might be beneficial in order to facilitate patient recovery during interval period. We propose a new technical paradigm for the ALPPS approach. During the first stage, partial parenchymal transection combined with intraoperative portal vein embolization (PVE) was performed. Liver mobilization was kept at minimum while hilar plate or hilum dissection was strictly avoided. The completion surgery by means of the anterior approach was carried out once sufficient future liver remnant (FLR) hypertrophy and function were certified. We applied this technique in four patients (hepatocellular carcinoma in a cirrhotic liver = 1 and colorectal liver metastases = 3). The mean FLR hypertrophy was 62.6 % (range 49–79). All the four patients underwent the completion surgery with R0 margins, and neither one developed liver failure nor major complications. The technique proposed inverts the current ALPPS strategy, minimizing the first stage impact to promote rapid patient recovery and leaving the main surgical procedure for the second stage. The combination of evidence-based facts such as partial parenchymal transection, intraoperative PVE, and “non-touch” oncological rules was feasible and safe, allowing complete tumor resection in highly selected candidates with extensive liver disease.

Backgrounds/aims Metastasis in the pancreatic gland is infrequent, representing between 2-5% of the tumors that affect this organ. However, secondary lesions of clear cell renal carcinoma (CCRC) can occur mainly in this location and it is frequently the only site of dissemination. Treatment of choice is resection in surgically fit patients, as it has been shown that it improves the quality of life and prognosis substantially. We retrospectively reviewed the clinical data of patients with pancreatic resections for metastatic CCRC since there are no reports of the treatment modality of this singular entity in Argentina. Methods Retrospective cohort analysis over a 10-year period including eight patients who underwent pancreatic resection for metastatic CCRC. Results 75% of patients were male with an average age of 65.5 years. The pancreatic surgery occurred at a median time of 9.2 years (1-24.8) from the renal operation. The pancreatic lesions were mostly solitary and asymptomatic. A pancreaticoduodenectomy (PD) was performed in 4 patients (50%). Distal pancreatectomy (DP) was performed in 3 patients (37.3%) and one patient (12.5%) underwent a total pancreaticoduodenectomy. All the patients presented a confirmatory biopsy of pancreatic metastasis of CCRC. Complications were recorded in 3 patients (42.85%). No intraoperative or postoperative mortality was registered. With a median follow-up of 45 months, three patients presented recurrence at 32, 46 and 51 months, respectively. Only one patient showed death due to recurrence at 7.8 month. Conclusions CCRC pancreatic metastases treated surgically have a low morbidity and mortality rate in high volume centers, showing excellent long-term survival.

Objective To evaluate the use of the caudal vena cava collapsibility index (CVCCI) as a predictor of fluid responsiveness in hospitalized, critically ill dogs with hemodynamic or tissue perfusion abnormalities. Design Retrospective observational study. Setting Private referral center. Animals Twenty-seven critically ill, spontaneously breathing dogs with compromised hemodynamics or tissue hypoperfusion. Interventions None. Measurements and main results The electronic medical records were searched for dogs admitted for any cause, from August 2016 to December 2017. We included dogs with ultrasound measurements of: CVCCI, performed at baseline; and velocity time integral (VTI) of the subaortic blood flow, carried out before and after a fluid load. CVCCI was estimated as: (maximum diameter-minimum diameter/maximum diameter) × 100. Dogs in which VTI increased ≥15% were considered fluid responders. The CVCCI accurately predicted fluid responsiveness with an area under the receiver operating characteristic curve of 0.96 (95% CI, 0.88 to 1.00). The optimal cut-off of CVCCI that better discriminated between fluid responders and nonresponders was 27%, with 100.0% sensitivity and 83.3% specificity. At baseline, fluid responders had lower VTI (5.48 [4.26 to 7.40] vs 10.61 [7.38 to 13.23] cm, P = 0.004) than nonresponders. The basal maximum diameter of the caudal vena cava adjusted to body weight was not different between responders and nonresponders (0.050 [0.030 to 0.100] vs 0.079 [0.067 to 0.140] cm/kg, P = 0.339). The increase in VTI was related to basal CVCCI (R = 0.60, P = 0.001). Bland-Altman analysis showed narrow 95% limits of agreement between measurements of CVCCI and VTI performed by different observers or by the same observer. Conclusions The results of this small cohort study suggest that CVCCI can accurately predict fluid responsiveness in critically ill dogs with perfusion abnormalities. Further research is necessary to extrapolate these results to larger populations of hospitalized dogs.

The initial mortality rates of associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) were high. However, recent data from the International Registry show a continuous reduction of early mortality and major morbidity due to risk adjustment in patient selection and less invasive techniques in stage-1 surgery. During the first ALPPS International Consensus in 2015, we introduced a paradigm inversion of ALPPS, the so-called "Mini-ALPPS."We combined a partial liver partition with a novel technique of laparoscopic-assisted percutaneous cannulation of the inferior mesenteric vein for intraoperative transmesenteric portal vein embolization. We report here for the first time, a case of a successful totally laparoscopic Mini-ALPPS, and describe in detail the technical aspects of this new approach.A 61-year-old man with a 6 cm hepatocellular carcinoma compromising the right glissonian pedicle in a fibrotic liver was treated by an extended right hepatectomy using the laparoscopic Mini-ALPPS approach. The patient had an uneventful first stage and was discharged 3 days after. A CT scan performed on postoperative day 8 showed sufficient future liver remnant volume after a 59% hypertrophy. An extended right hepatectomy was uneventfully completed and the patient was discharged 5 days after surgery. The histopathological analysis indicated advanced F4 liver fibrosis and negative tumor margins.This technical innovation allows avoiding a laparotomy to access the mesenteric venous territory and the risks of liver remnant injuries during percutaneous transhepatic approach. This new alternative may result of great utility not only in ALPPS but also for many different circumstances and scenarios.

Background/Aims: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations influence survival after hepatectomy for colorectal liver metastases (CRLM). However, their prognostic significance has never been evaluated in patients who undergo Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS). Methods: Between June 2011 and March 2016, 26 patients underwent ALPPS for CRLM. Complications were classified according to the Clavien-Dindo classification. Bi- and multivariate cox analyses were performed to evaluate variables potentially associated with survival. Results: Overall, morbidity grade ≥3a and 90-day mortality were 38.5 and 0%, respectively. The median follow-up from the time of discharge was 21.5 months (interquartile range 9.6-35.6). One- and 3-year overall survival (OS) was 83.4 and 48.9%, respectively. Patients with mutated (MT) KRAS had a median OS of 15.3 vs. 38.3 months for those with wild-type (WT) KRAS (p < 0.0001). Median disease-free survival was 7.9, 5.6 vs. 12.3 months for MT and WT KRAS, respectively (p = 0.023). KRAS mutation was found to be an independent risk factor for OS (hazard ratio 7.15, 95% CI 1.50-34.11; p = 0.014). Conclusion: KRAS mutation is an independent predictor of poor survival after ALPPS. This finding will help to optimize patient selection, both avoiding futile surgical indication and maximizing the benefit for patients with extensive disease who are otherwise subjected to high-risk aggressive surgery.

OBJECTIVES: The aim of this study was to identify predictors of 90-day mortality after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), available after stage-1, either to omit or delay stage-2. BACKGROUND DATA: ALPPS is a two-stage hepatectomy for patients with extensive liver tumors with predicted small liver remnants, which has been criticized for its high mortality rate. Risk factors for mortality are unknown. METHODS: Patients in the International Registry undergoing ALPPS from April 2011 to July 2014 were analyzed. Primary outcome was 90-day mortality. Liver function after stage-1 was assessed using the criteria of the International Study Group for Liver Surgery (ISGLS) after stage-1 among others. A multivariable model was used to identify independent predictors of 90-day mortality. RESULTS: Three hundred twenty patients registered by 55 centers worldwide were evaluated. Overall 90-day mortality was 8.8% (28/320). The predominant cause for 90-day mortality was postoperative liver failure in 75% of patients. Fourteen percent of patients developed liver failure according to ISGLS criteria already after stage-1 ALPPS. Those and patients with a model of end-stage liver disease (MELD) score more than 10 before stage-2 were at significantly higher risk for 90-day mortality after stage-2 with an odds ratio (OR) 3.9 [confidence interval (CI) 1.4-10.9, P = 0.01] and OR 4.9 (CI 1.9-12.7, P = 0.006), respectively. Other factors, such as size of future liver remnant (FLR) before stage-2 and time between stages, were not predictive. CONCLUSIONS: This analysis of the largest cohort of ALPPS patients so far identifies those patients in whom stage-2 ALPPS surgery should be delayed or even denied. These findings may help to make ALPPS safer.

The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) strategy induces rapid future liver remnant (FLR) hypertrophy. Hepatocyte cellular and molecular changes associated with liver hypertrophy during ALPPS remain ill-defined in humans.Patients undergoing the ALPPS approach between June 2011 and October 2014 were extracted. Biopsies from the FLR were obtained during the first and second stages. Hematoxylin-eosin staining and immunohistochemical analysis for expression of the proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were performed. The proliferative index was defined as: PCNA-TUNEL ratio.Eleven of 34 patients treated were studied during both stages. Median FLR hypertrophy was 104 % in 6 days, with a mean difference between preoperative and postoperative volume of 361 ml (P 0.001). The mean hepatocyte number increased from 52.7 cells/mm(2) in the first stage to 89.6 cells/mm(2) in the second stage (P = 0.001). PCNA expression increased by 190 % between stages with a linear correlation (r = 0.58) with macroscopic hypertrophy. The proliferative index increased from -3.78 cells/mm(2) in first stage to 2.32 cells/mm(2) in the second stage (P = 0.034).The results of the present study indicate that the rapid FLR volumetric increase observed in ALPPS is accompanied by histological and molecular features of hepatocyte cell proliferation.

To determine the safety, feasibility, and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in a single high-volume hepatobiliary center.The ALPPS approach allows achieving resectability of liver malignancies by a rapid and large future liver remnant (FLR) hypertrophy. However, this proposal has been associated with high morbidity and mortality rates.This was a single-cohort, prospective, observational study [NCT02164292]. Between June 2011 and April 2014, patients with liver malignancies considered unresectable due to an insufficient FLR who underwent ALPPS were included.Thirty patients were treated. Median age was 58.6 years (range = 35-81) and 19 patients were males (63%). In a median of 6 days (range = 4-67), the median FLR hypertrophy was 89.7% (range = 21-287). Twenty-nine patients completed the second stage (97% feasibility). Morbidity according to the Dindo-Clavien classification was 53% (grade ≥IIIa 43% and grade ≥IIIb 31%). The mortality rate was 6.6%. Total parenchymal transection was identified as an independent risk factor for complications (P = 0.049). There was not significant difference in terms of FLR hypertrophy between total or partial parenchymal transection (P = 0.45). Median hospital stay was 16 days (range = 11-62). The overall and disease-free survival at 1 year was 78% and 67% and at 2 years was 63% and 40%, respectively.This prospective study on the largest reported single-center experience shows that ALPPS has acceptable morbidity and mortality, together with a high oncological feasibility and hypertrophic efficacy. Partial parenchymal transection seems to reduce morbidity without negatively impacting FLR hypertrophy.

Common bile duct injuries (CBDI) are serious complications of cholecystectomies which are often associated with vascular involvement, meaning that their management represents a major challenge to the physician. We present our experience in major hepatectomy due to CBDI, highlighting indications, postoperative complications, and long-term outcomes. From August 1993 to September 2013, 287 patients with CBDI were treated in our centre. In 15 patients of this group (5 %), a major hepatectomy was performed. Eleven patients presented E4 and four presented E5 injuries of Strasberg classification. Seven patients presented vascular involvement. In 12 patients, prior treatment attempts, either biliodigestive anastomosis, endoscopic or percutaneous drainage, was performed without success. The median time delay between lesional surgery and hepatectomy was 24 months. Right hepatectomy was performed in 10 patients and left hepatectomy in 5. Postoperative morbidity was 60 %. The incidence of serious complications (≥grade IIIa of DC classification) was 40 %. There was no mortality in our study. The mean follow-up was 43.5 months and the overall survival was 100 %. Three patients had a single episode of ascendant cholangitis who were successfully treated with medical treatment. All other patients were asymptomatic during follow-up. No patients required further surgical procedures. In our series, major hepatectomy due to CBDI was a successful treatment with high rates of postoperative morbidity and excellent long-term outcomes which require a multidisciplinary approach in referral centres of HPB surgery.

Background: Although several studies relate frailty with poor postoperative outcomes, trials with specific intraabdominal surgery cohorts are scarce.

The management of colorectal liver metastases has evolved over the past decades, with more patients now being offered surgery. The use of modern chemotherapeutic and adjunct techniques to surgery has contributed greatly to improve resectability rates and outcomes. As a consequence, patients with advanced CLM are living longer than they did previously due to these major advances in treatment. The surgical strategy should be tailored according to the existence of both patient and liver-related operative risks. From a technical perspective, the availability of state-of-the-art abdominal imaging is crucial to define resectability and to plan the optimal surgical procedure. Associating an acceptable patient risk with a safe technical proposal and a reasonable oncological indication should be the goal of liver surgeons when selecting candidates for surgery. Patient treatment should be routinely discussed by a multidisciplinary tumor board including colorectal surgeons, liver surgeons, oncologists, radiation oncologists, radiologists, and pathologists. Such a multidisciplinary approach has been demonstrated to offer better patient care and survival outcomes, as well as improved consistency, continuity, coordination, and cost-effectiveness of treatment.

In the last 2 decades, the results of hepatic resections (HR) have significantly improved. This improvement was possible because of the development of new anesthetic techniques, better postoperative care, better patient selection, the development of new technological devices and the specialization of hepatobiliary surgery units. The low mortality in referral centers has extended indication for HRs, allowing surgeons to perform extreme procedures in patients considered unresectable 20 years ago. These extreme procedures include associated vascular resections and reconstruction, ex vivo surgeries and the simultaneous resection of adjacent organs. The incidence of complications and perioperative mortality varies in the literature, between 15–45% and 0–25% respectively. The different criteria used to define morbidity as well as the inclusion (or not) of mild complications (Dindo-Clavien’s Grade 1 and 2) explains in part the variability of morbidity rates in the literature. Different factors have been associated with the development of postoperative complications: blood loss, number of resected segments, preoperative hypoalbuminemia, renal insufficiency, associated biliary procedures, associated vascular procedures, male gender and associated patients comorbidities. In addition, the experience of the surgical team, type of tumor, the moment of indication (elective, urgency, emergency resection), extent of resection, parenchymal quality of the liver (steatosis, steatohepatitis, fibrosis, cirrhosis, post-chemotherapy changes) and patient selection are also key aspects. Reoperations to solve postoperative complications vary between 3 and 19%. The most frequent cause of reoperations is postoperative bleeding and intra-abdominal collections. In this chapter, local specific postoperative complications related to HR are described along with their specific management and prevention.

At diagnosis, 15–25% of patients with stage IV colon cancer have synchronous detected liver metastases. About 30% of patients are not initially resectable due to the extent of hepatic disease or a small future liver remnant (FLR). When size of FLR is regarded to be not sufficient to sustain liver function in the postoperative course, techniques of portal vein occlusion (PVO) such as portal vein embolization (PVE) or portal vein ligation (PVL) can be used in the context of a classic two-stage hepatectomy (TSH) to get increase of the residual liver. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel two-stage technique which combines PVO and parenchymal transection, followed by hepatectomy in a shorter period of time than classical TSH. However, many concerns have been addressed to the safety of this procedure. Further refinements of the original technique have been explored to improve its results. We report herein the case of a 44-year-old female patient with an obstructive cancer of the sigmoid colon and synchronous bilateral colorectal liver metastases, treated with the so-called “mini-ALPPS” approach.