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BACKGROUND: While resection remains the only curative option for perihilar cholangiocarcinoma, it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in perihilar cholangiocarcinoma surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered. METHODS: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided into a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome. RESULTS: A total of 2271 cases were analyzed: among them, 309 were classified within the "futile group" (13.6%). American Society of Anesthesiology (ASA) score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥3 cm (OR 1.76; p < 0.001), and left-sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (ie, low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort. CONCLUSIONS: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. nonsurgical treatments) according to preoperative features.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colangite , Tumor de Klatskin , Humanos , Tumor de Klatskin/cirurgia , Tumor de Klatskin/complicações , Futilidade Médica , Recidiva Local de Neoplasia/etiologia , Colangite/complicações , Hepatectomia/métodos , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: We sought to develop and validate a preoperative model to predict survival after recurrence (SAR) in hepatocellular carcinoma (HCC). BACKGROUND: Although HCC is characterized by recurrence as high as 60%, models to predict outcomes after recurrence remain relatively unexplored. METHODS: Patients who developed recurrent HCC between 2000 and 2020 were identified from an international multi-institutional database. Clinicopathologic data on primary disease and laboratory and radiologic imaging data on recurrent disease were collected. Multivariable Cox regression analysis and internal bootstrap validation (5000 repetitions) were used to develop and validate the SARScore. Optimal Survival Tree analysis was used to characterize SAR among patients treated with various treatment modalities. RESULTS: Among 497 patients who developed recurrent HCC, median SAR was 41.2 months (95% CI 38.1-52.0). The presence of cirrhosis, number of primary tumors, primary macrovascular invasion, primary R1 resection margin, AFP>400 ng/mL on the diagnosis of recurrent disease, radiologic extrahepatic recurrence, radiologic size and number of recurrent lesions, radiologic recurrent bilobar disease, and early recurrence (≤24 months) were included in the model. The SARScore successfully stratified 1-, 3- and 5-year SAR and demonstrated strong discriminatory ability (3-year AUC: 0.75, 95% CI 0.70-0.79). While a subset of patients benefitted from resection/ablation, Optimal Survival Tree analysis revealed that patients with high SARScore disease had the worst outcomes (5-year AUC; training: 0.79 vs. testing: 0.71). The SARScore model was made available online for ease of use and clinical applicability ( https://yutaka-endo.shinyapps.io/SARScore/ ). CONCLUSION: The SARScore demonstrated strong discriminatory ability and may be a clinically useful tool to help stratify risk and guide treatment for patients with recurrent HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Prognóstico , Recidiva Local de Neoplasia/patologia , Análise de Sobrevida , Estudos RetrospectivosRESUMO
OBJECTIVES: To define how dynamic changes in pre- versus post-operative serum aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels may impact postoperative morbidity after curative-intent resection of hepatocellular carcinoma (HCC). BACKGROUND: Hepatic ischemia/reperfusion can occur at the time of liver resection and may be associated with adverse outcomes following liver resection. METHODS: Patients who underwent curative resection for HCC between 2010-2020 were identified from an international multi-institutional database. Changes in AST and ALT (CAA) on postoperative day (POD) 3 versus preoperative values () were calculated using the formula: based on a fusion index via Euclidean norm, which was examined relative to the comprehensive complication index (CCI). The impact of CAA on CCI was assessed by the restricted cubic spline regression and Random Forest analyses. RESULTS: A total of 759 patients were included in the analytic cohort. Median CAA was 1.7 (range, 0.9 to 3.25); 431 (56.8%) patients had a CAA<2, 215 (28.3%) patients with CAA 2-5, and 113 (14.9%) patients had CAA ≥5. The incidence of post-operative complications was 65.0% (n=493) with a median CCI of 20.9 (IQR, 20.9-33.5). Spline regression analysis demonstrated a non-linear incremental association between CAA and CCI. The optimal cutoff value of CAA=5 was identified by the recursive partitioning technique. After adjusting for other competing risk factors, CAA≥5 remained strongly associated with risk of post-operative complications (Ref. CAA<5, OR 1.63, 95%CI 1.05-2.55, P=0.03). In fact, the use of CAA to predict post-operative complications was very good in both the derivative (AUC 0.88) and external (ACU 0.86) cohorts (n=1137). CONCLUSIONS: CAA was an independent predictor of CCI after liver resection for HCC. Use of routine labs such as AST and ALT can help identify patients at highest risk of post-operative complications following HCC resection.
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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 Ë0.01), 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.
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Neoplasias Hepáticas , Regeneração Hepática , Humanos , Hepatectomia/efeitos adversos , Estudos de Coortes , Veia Porta/cirurgia , Fígado/cirurgia , Fígado/patologia , Neoplasias Hepáticas/secundário , Ligadura , Resultado do TratamentoRESUMO
OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.
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BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Síndrome Metabólica , Humanos , Hepatectomia/métodos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Surgery for intrahepatic cholangiocarcinoma (iCCA) is jeopardized by significant risk of early recurrence (≤ 6 months). The aim of the present study is to analyze the oncological benefit provided by laparoscopic over open approach for iCCA in patients with high risk of very early recurrence (VER). MATERIALS AND METHODS: A total of 532 liver resections (LR) were performed for iCCA [265 by minimally invasive surgery (MIS) and 267 with open approach, matched through a 1:1 propensity score] and stratified using the postoperative prediction model of VER. Outcomes were compared between open and laparoscopic approaches, specifically evaluating oncological benefit. RESULTS: The percentage of patients with high risk of VER was similar (32.7% in the laparoscopic group and 35.3% in the open group, pNS). The number of retrieved nodes as well as the rate and depth of negative resection margins were comparable between laparoscopic and open. The surgery-adjuvant treatment interval was shorter in laparoscopic patients in the overall series, as well in the subgroup of high risk of VER. The rate of patients starting adjuvant treatments within 2 months from surgery was higher in laparoscopic group compared with open group. In VER high-risk group both disease-free survival (DFS) and overall survival (OS) were significantly improved in MIS compared with open group (p = 0.032 and p = 0.026, respectively). CONCLUSIONS: In patients with high risk of VER, laparoscopy translates into an advantage in terms of recurrence-free survival, likely related to lower biological impact of surgery, together with a shorter interval between surgery and start of adjuvant treatments, even allowing for a higher number of patients to start adjuvant therapies within 2 months from resection.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Laparoscopia , Humanos , Colangiocarcinoma/cirurgia , Hepatectomia , Intervalo Livre de Doença , Ductos Biliares Intra-Hepáticos/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) constitutes a group of heterogeneous malignancies within the liver. We sought to subtype ICC based on anatomical origin of tumors, as well as propose modifications of the current classification system. METHODS: Patients undergoing curative-intent resection for ICC, hilar cholangiocarcinoma (CCA), or hepatocellular carcinoma (HCC) were identified from three international multi-institutional consortia of databases. Clinicopathological characteristics and survival outcomes were assessed. RESULTS: Among 1264 patients with ICC, 1066 (84.3%) were classified as ICC-peripheral subtype, whereas 198 (15.7%) were categorized as ICC-perihilar subtype. Compared with ICC-peripheral subtype, ICC-perihilar subtype was more often associated with aggressive tumor characteristics, including a higher incidence of nodal metastasis, macro- and microvascular invasion, perineural invasion, as well as worse overall survival (OS) (median: ICC-perihilar 19.8 vs. ICC-peripheral 37.1 months; p < 0.001) and disease-free survival (DFS) (median: ICC-perihilar 12.8 vs. ICC-peripheral 15.2 months; p = 0.019). ICC-perihilar subtype and hilar CCA had comparable OS (19.8 vs. 21.4 months; p = 0.581) and DFS (12.8 vs. 16.8 months; p = 0.140). ICC-peripheral subtype tumors were associated with more advanced tumor features, as well as worse survival outcomes versus HCC (OS, median: ICC-peripheral 37.1 vs. HCC 74.3 months; p < 0.001; DFS, median: ICC-peripheral 15.2 vs. HCC 45.5 months; p < 0.001). CONCLUSIONS: ICC should be classified as ICC-perihilar and ICC-peripheral subtype based on distinct clinicopathological features and survival outcomes. ICC-perihilar subtype behaved more like carcinoma of the bile duct (i.e., hilar CCA), whereas ICC-peripheral subtype had features and a prognosis more akin to a primary liver malignancy.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Colangiocarcinoma/patologia , Prognóstico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologiaRESUMO
BACKGROUND: Recurrence of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR) remains high, and optimal therapy for recurrent ICC is challenging. Herein, we assess the outcomes of patients undergoing repeat resection for recurrent ICC in a large, international multicenter cohort. PATIENTS AND METHODS: Outcomes of adults from six large hepatobiliary centers in North America, Europe, and Asia with recurrent ICC following primary LR between 2001 and 2015 were analyzed. Cox models determined predictors of post-recurrence survival. RESULTS: Of patients undergoing LR for ICC, 499 developed recurrence. The median time to recurrence was 10 months, and 47% were intrahepatic. Overall 3-year post-recurrence survival rate was 28.6%. In total, 121 patients (25%) underwent repeat resection, including 74 (61%) repeat LRs. Surgically treated patients were more likely to have solitary intrahepatic recurrences and significantly prolonged survival compared with those receiving locoregional or systemic therapy alone with a 3-year post-recurrence survival rate of 47%. Independent predictors of post-recurrence death included time to recurrence < 1 year [HR 1.66 (1.32-2.10), p < 0.001], site of recurrence [HR 1.74 (1.28-2.38), p < 0.001], macrovascular invasion [HR 1.43 (1.05-1.95), p = 0.024], and size of recurrence > 3 cm [HR 1.68 (1.24-2.29), p = 0.001]. Repeat resection was independently associated with decreased post-recurrence death [HR 0.58 0.43-0.78), p < 0.001]. CONCLUSIONS: Repeat resection for recurrent ICC in select patients can result in extended survival. Thus, challenging the paradigm of offering these patients locoregional or chemo/palliative therapy alone as the mainstay of treatment.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatectomia , Recidiva Local de Neoplasia , Reoperação , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Masculino , Feminino , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Hepatectomia/mortalidade , Hepatectomia/métodos , Taxa de Sobrevida , Pessoa de Meia-Idade , Idoso , Reoperação/estatística & dados numéricos , Seguimentos , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Although up to 50-70% of patients with intrahepatic cholangiocarcinoma (ICC) recur following resection, data to predict post-recurrence survival (PRS) and guide treatment of recurrence are limited. METHODS: Patients who underwent resection of ICC between 2000 and 2020 were identified from an international, multi-institutional database. Data on primary disease as well as laboratory and radiologic data on recurrent disease were collected. Factors associated with PRS were examined and a novel scoring system to predict PRS (PRS score) was developed and internally validated. RESULTS: Among 986 individuals who underwent resection for ICC, 588 (59.6%) patients developed recurrence at a median follow up of 20.3 months. Among patients who experienced a recurrence, 97 (16.5%) underwent re-resection/ablation for recurrent ICC; 88 (15.0%) and 403 (68.5%) patients received intra-arterial treatment or systemic chemotherapy/supportive therapy, respectively. Patient American Society of Anesthesiologists (ASA) class > 2 (1 point), primary tumor N1/Nx status (1 point), primary R1 resection margin (1 point), primary tumor G3/G4 grade (1 point), carbohydrate antigen (CA) 19-9 > 37 UI/mL (2 points) at recurrence and carcinoembryonic antigen (CEA) > 5 ng/mL (2 points) at recurrence, as well as recurrent bilateral disease (1 point) and early recurrence (1 point) were included in the PRS score. The PRS score successfully stratified patients relative to PRS and demonstrated strong discriminatory ability (C-index 0.70, 95% confidence interval 0.68-0.72). While a PRS score of 0-3 was associated with a 3-year PRS of 62.5% following resection/ablation for recurrent ICC, a PRS score > 3 was associated with a low 3-year PRS of 35.5% (p = 0.03). CONCLUSIONS: The PRS score demonstrated strong discriminatory ability to predict PRS among patients who had developed recurrence following initial resection of ICC. The PRS score may be a useful tool to guide treatment among patients with recurrent ICC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Recidiva Local de Neoplasia , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Feminino , Masculino , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/mortalidade , Pessoa de Meia-Idade , Taxa de Sobrevida , Idoso , Seguimentos , Hepatectomia/mortalidade , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Immune dysregulation may be associated with cancer progression. We sought to investigate the prognostic value of perioperative lymphopenia on short- and long-term outcomes among patients undergoing resection of hepatocellular carcinoma (HCC). METHODS: Patients undergoing resection of HCC between 2000 and 2020 were identified using an international database. The incidence and impact of perioperative lymphopenia [preoperative, postoperative day (POD) 1/3/5], defined as absolute lymphocyte count (ALC) <1000/µL, on short- and long-term outcomes was assessed. RESULTS: Among 1448 patients, median preoperative ALC was 1593/µL [interquartile range (IQR) 1208-2006]. The incidence of preoperative lymphopenia was 14.0%, and 50.2%, 45.1% and 35.6% on POD1, POD3 and POD5, respectively. Preoperative lymphopenia predicted 5-year overall survival (OS) [lymphopenia vs. no lymphopenia: 49.1% vs. 66.1%] and 5-year disease-free survival (DFS) [25.0% vs. 41.5%] (both p < 0.05). Lymphopenia on POD1 (5-year OS: 57.1% vs. 71.2%; 5-year DFS: 30.0% vs. 41.1%), POD3 (5-year OS: 57.3% vs. 68.9%; 5-year DFS: 35.4% vs. 42.7%), and POD5 (5-year OS: 53.1% vs. 66.1%; 5-year DFS: 32.8% vs. 42.3%) was associated with worse long-term outcomes (all p < 0.05). Patients with severe lymphopenia (ALC <500/µL) on POD5 had worse 5-year OS and DFS (5-year OS: 44.7% vs. 54.3% vs. 66.1%; 5-year DFS: 27.8% vs. 33.3% vs. 42.3%) [both p < 0.05], as well as higher incidence of overall (45.5% vs. 25.3% vs. 30.9%; p = 0.013) and major complications (18.2% vs. 3.4% vs. 4.5%; p < 0.001) versus individuals with moderate (ALC 500-1000/µL) or no lymphopenia following hepatectomy for HCC. After adjusting for competing risk factors, prolonged lymphopenia was independently associated with higher hazards of death [hazard ratio (HR) 1.38, 95% CI 1.11-1.72] and recurrence (HR 1.22, 95% CI 1.02-1.45). CONCLUSION: Perioperative lymphopenia had short- and long-term prognostic implications among individuals undergoing hepatectomy for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Linfopenia , Humanos , Carcinoma Hepatocelular/patologia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Linfopenia/etiologia , Prognóstico , Intervalo Livre de DoençaRESUMO
INTRODUCTION: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. METHODS: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class <3, body mass index <35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. RESULTS: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0-67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. CONCLUSIONS: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Pessoa de Meia-Idade , Ductos Biliares Intra-Hepáticos/patologia , Benchmarking , Hepatectomia/métodos , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited. METHODS: Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (>50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases. RESULTS: Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p < 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients. CONCLUSIONS: Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/genética , Colangiocarcinoma/cirurgia , Prognóstico , Perfilação da Expressão Gênica , Hepatectomia , Genômica , Ductos Biliares Intra-Hepáticos/patologia , Antígenos de Histocompatibilidade Menor , Histona DesmetilasesRESUMO
BACKGROUND: Minimally invasive liver resections (MILR) offer potential benefits such as reduced blood loss and morbidity compared with open liver resections. Several studies have suggested that the impact of cirrhosis differs according to the extent and complexity of resection. Our aim was to investigate the impact of cirrhosis on the difficulty and outcomes of MILR, focusing on major hepatectomies. METHODS: A total of 2534 patients undergoing minimally invasive major hepatectomies (MIMH) for primary malignancies across 58 centers worldwide were retrospectively reviewed. Propensity score (PSM) and coarsened exact matching (CEM) were used to compare patients with and without cirrhosis. RESULTS: A total of 1353 patients (53%) had no cirrhosis, 1065 (42%) had Child-Pugh A and 116 (4%) had Child-Pugh B cirrhosis. Matched comparison between non-cirrhotics vs Child-Pugh A cirrhosis demonstrated comparable blood loss. However, after PSM, postoperative morbidity and length of hospitalization was significantly greater in Child-Pugh A cirrhosis, but these were not statistically significant with CEM. Comparison between Child-Pugh A and Child-Pugh B cirrhosis demonstrated the latter had significantly higher transfusion rates and longer hospitalization after PSM, but not after CEM. Comparison of patients with cirrhosis of all grades with and without portal hypertension demonstrated no significant difference in all major perioperative outcomes after PSM and CEM. CONCLUSIONS: The presence and severity of cirrhosis affected the difficulty and impacted the outcomes of MIMH, resulting in higher blood transfusion rates, increased postoperative morbidity, and longer hospitalization in patients with more advanced cirrhosis. As such, future difficulty scoring systems for MIMH should incorporate liver cirrhosis and its severity as variables.
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Hipertensão Portal , Laparoscopia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Hepatectomia/métodos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Cirrose Hepática/patologia , Laparoscopia/métodos , Hipertensão Portal/etiologia , Hipertensão Portal/cirurgia , Tempo de Internação , Pontuação de PropensãoRESUMO
BACKGROUND: Laparoscopic liver surgery is increasingly used for more challenging procedures. The aim of this study was to assess the feasibility and oncological safety of laparoscopic right hepatectomy for colorectal liver metastases after portal vein embolization. METHODS: This was an international retrospective multicentre study of patients with colorectal liver metastases who underwent open or laparoscopic right and extended right hepatectomy after portal vein embolization between 2004 and 2020. The perioperative and oncological outcomes for patients who underwent laparoscopic and open approaches were compared using propensity score matching. RESULTS: Of 338 patients, 84 patients underwent a laparoscopic procedure and 254 patients underwent an open procedure. Patients in the laparoscopic group less often underwent extended right hepatectomy (18% versus 34.6% (P = 0.004)), procedures in the setting of a two-stage hepatectomy (42% versus 65% (P < 0.001)), and major concurrent procedures (4% versus 16.1% (P = 0.003)). After propensity score matching, 78 patients remained in each group. The laparoscopic approach was associated with longer operating and Pringle times (330 versus 258.5 min (P < 0.001) and 65 versus 30 min (P = 0.001) respectively) and a shorter length of stay (7 versus 8 days (P = 0.011)). The R0 resection rate was not different (71% for the laparoscopic approach versus 60% for the open approach (P = 0.230)). The median disease-free survival was 12 (95% c.i. 10 to 20) months for the laparoscopic approach versus 20 (95% c.i. 13 to 31) months for the open approach (P = 0.145). The median overall survival was 28 (95% c.i. 22 to 48) months for the laparoscopic approach versus 42 (95% c.i. 35 to 52) months for the open approach (P = 0.614). CONCLUSION: The advantages of a laparoscopic over an open approach for (extended) right hepatectomy for colorectal liver metastases after portal vein embolization are limited.
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Neoplasias Colorretais , Embolização Terapêutica , Hepatectomia , Laparoscopia , Neoplasias Hepáticas , Veia Porta , Humanos , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/patologia , Laparoscopia/métodos , Masculino , Feminino , Veia Porta/cirurgia , Embolização Terapêutica/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Pontuação de Propensão , Resultado do Tratamento , Estudos de Viabilidade , Tempo de InternaçãoRESUMO
OBJECTIVES: The objective of the current study was to characterize prognostic factors related to long-term recurrence-free survival after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). METHODS: Data on patients who underwent curative-intent resection for ICC between 2000 and 2020 were collected from an international multi-institutional database. Prognostic factors were investigated among patients who recurred within 5 years versus long-term survivors who survived more than 5 years with no recurrence. RESULTS: Among 635 patients who underwent curative-intent resection for ICC, 104 (16.4%) patients were long-term survivors with no recurrence beyond 5 years after surgery. Patients who survived for more than 5 years with no recurrence were more likely to have less aggressive tumor features, as well as have undergone an R0 resection versus patients who recurred within 5 years after resection. On multivariable analysis, tumor size (>5 cm) (HR: 1.535, 95% CI: 1.254-1.879), satellite lesions (HR: 1.253, 95% CI: 1.003-1.564), and lymph node metastasis (HR: 1.733, 95% CI: 1.349-2.227) were independently associated with recurrence within 5 years. Patients who recurred beyond 5 years (n = 23), 2-5 years (n = 60), and within 2 years (n = 471) had an incrementally worse post-recurrence survival (PRS, 28.0 vs. 20.0 vs. 12.0 months, p = 0.032). Among patients with N0 status, tumor size (>5 cm) (HR: 1.612, 95% CI: 1.087-2.390) and perineural invasion (PNI) (HR: 1.562,95% CI: 1.081-2.255) were risk factors associated with recurrence. Among patients with N1 disease, only a minority (5/128, 3.9%) of patients survived with no recurrence to 5 years. CONCLUSION: Roughly 1 in 6 patients survived for more than 5 years with no recurrence following curative-intent resection of ICC. Among N0 patients, tumor recurrence was associated with tumor size and PNI. Only a small subset of N1 patients experienced long-term survival.
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BACKGROUND AND OBJECTIVES: An elevated platelet count may reflect neoplastic and inflammatory states, with cytokine-driven overproduction of platelets. The objective of this study was to evaluate the prognostic utility of high platelet count among patients undergoing curative-intent liver surgery for intrahepatic cholangiocarcinoma (ICC). METHODS: An international, multi-institutional cohort was used to identify patients undergoing curative-intent liver resection for ICC (2000-2020). A high platelet count was defined as platelets >300 *109/L. The relationship between preoperative platelet count, cancer-specific survival (CSS), and overall survival (OS) was examined. RESULTS: Among 825 patients undergoing curative-intent resection for ICC, 139 had a high platelet count, which correlated with multifocal disease, lymph nodes metastasis, poor to undifferentiated grade, and microvascular invasion. Patients with high platelet counts had worse 5-year (35.8% vs. 46.7%, p = 0.009) CSS and OS (24.8% vs. 39.8%, p < 0.001), relative to patients with a low platelet count. After controlling for relevant clinicopathologic factors, high platelet count remained an adverse independent predictor of CSS (HR = 1.46, 95% CI 1.02-2.09) and OS (HR = 1.59, 95% CI 1.14-2.22). CONCLUSIONS: High platelet count was associated with worse tumor characteristics and poor long-term CSS and OS. Platelet count represents a readily-available laboratory value that may preoperatively improve risk-stratification of patients undergoing curative-intent liver resection for ICC.
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BACKGROUND: Hepatic resection combined with intraoperative ablation has been described as a technical solution potentially widening the resectability rate of patients with colorectal liver metastases (CRLM). Nevertheless, the perioperative and oncological benefit provided by this combined approach remains unclear. We hypothesized that textbook outcome (TO), which is a composite measure achieved for patients for whom some desired health indicators are met, may help to refine the indications of this approach. METHODS: Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM ≤ 3 cm in two tertiary referral centers were included. TO was defined according to a recent definition for liver surgery based on a Delphi process including also the achievement of complete radiological response of the ablated lesion/s at 4 weeks. RESULTS: Between 2015 and 2022, 112 patients were enrolled. Among them, 63 (56.2%) achieved a TO. According to multivariate analysis, minimally invasive (MI) approach (OR 2.72, 95% CI 0.99-7.48, p = 0.050), simultaneous CR resection (OR 0.28, 95% CI 0.11-0.70, p = 0.007), tumor burden score (OR 0.89, 95% CI 0.82-0.96, p = 0.004), and major hepatectomy (OR 0.12, 95% CI 0.03-0.52, p = 0.004) were significantly associated with the achievement of TO. Median overall survival was longer in those patients who were able to achieve a TO compared to those who did not. CONCLUSIONS: The combination of hepatectomy and ablation constitutes a valuable solution in patients affected by multiple CRLM and it may provide, also using a MI approach, adequate perioperative and oncological outcomes, allowing to achieve TO, however, in a selected number of patients and depending on several factors including the burden of disease.
Assuntos
Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Hepatectomia/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Ablação por Radiofrequência/métodos , Estudos Retrospectivos , Ablação por Cateter/métodos , Micro-Ondas/uso terapêuticoRESUMO
PURPOSE: Radiomics may aid in predicting prognosis in patients with colorectal liver metastases (CLM). Consistent data is available on CT, yet limited data is available on MRI. This study assesses the capability of MRI-derived radiomic features (RFs) to predict local tumor progression-free survival (LTPFS) in patients with CLMs treated with microwave ablation (MWA). METHODS: All CLM patients with pre-operative Gadoxetic acid-MRI treated with MWA in a single institution between September 2015 and February 2022 were evaluated. Pre-procedural information was retrieved retrospectively. Two observers manually segmented CLMs on T2 and T1-Hepatobiliary phase (T1-HBP) scans. After inter-observer variability testing, 148/182 RFs showed robustness on T1-HBP, and 141/182 on T2 (ICC > 0.7).Cox multivariate analysis was run to establish clinical (CLIN-mod), radiomic (RAD-T1, RAD-T2), and combined (COMB-T1, COMB-T2) models for LTPFS prediction. RESULTS: Seventy-six CLMs (43 patients) were assessed. Median follow-up was 14 months. LTP occurred in 19 lesions (25%).CLIN-mod was composed of minimal ablation margins (MAMs), intra-segment progression and primary tumor grade and exhibited moderately high discriminatory power in predicting LTPFS (AUC = 0.89, p = 0.0001). Both RAD-T1 and RAD-T2 were able to predict LTPFS: (RAD-T1: AUC = 0.83, p = 0.0003; RAD-T2: AUC = 0.79, p = 0.001). Combined models yielded the strongest performance (COMB-T1: AUC = 0.98, p = 0.0001; COMB-T2: AUC = 0.95, p = 0.0003). Both combined models included MAMs and tumor regression grade; COMB-T1 also featured 10th percentile of signal intensity, while tumor flatness was present in COMB-T2. CONCLUSION: MRI-based radiomic evaluation of CLMs is feasible and potentially useful for LTP prediction. Combined models outperformed clinical or radiomic models alone for LTPFS prediction.
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Neoplasias Colorretais , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Progressão da Doença , Adulto , RadiômicaRESUMO
BACKGROUND: The introduction into the clinical practice of the navigator nurse (NaNu) to address the task of counseling and short term follow-up help the effective implementation of the fast track protocol. The aim of the present study was to investigate the impact of the standardization of the NaNu's role in patients undergoing liver surgery. METHODS: Patients undergoing elective liver surgery for all diagnosis and approach, from 2015, received counseling and postoperative follow-up by NaNu and constituted the study group (n = 890). This group was compared with the control group (n = 712) including patients treated in the era before the implementation of the NaNu role (2011-2014). Outcome was evaluated in terms of discrepancy between functional recovery and discharge, number of ER accesses, number of readmissions. RESULTS: Preoperative characteristics of patients and disease, as well as type of resection and postoperative outcomes were similar between the two groups. The proportion of laparoscopic cases was higher in the study group (51.2% vs. 32% in the control). Time for discharge, interval between functional recovery and discharge, number of ER accesses and number of readmissions were reduced in the study group. Benign diagnosis, absence of complications, laparoscopic approach and presence of NaNu were independent predictors of shorter length of stay. The positive effect of NaNu's activation was recorded in patients with complications and undergoing open surgery. CONCLUSION: The implementation of NaNu's role has allowed to us optimize the level of healthcare service offered to patients. The wider benefit was offered in the setting of complex patients.