RESUMO
OBJECTIVE: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. BACKGROUND: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.
Assuntos
Hepatectomia , Laparoscopia , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Humanos , Hepatectomia/métodos , Feminino , Masculino , Laparoscopia/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Hepatopatias/cirurgiaRESUMO
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: Tumors at the hepatocaval confluence can be treated with parenchyma-sparing surgery, also with minimally invasive approach.1,2 The "Liver Tunnel" was described for tumors involving the paracaval portion of Sg1 in contact or infiltrating the middle hepatic vein (MHV).3 A "Liver Tunnel" with laparoscopic approach is proposed. METHODS: A 48-year-old woman was referred for three synchronous colorectal liver metastases in the paracaval portion of Sg1 in contact with the inferior vena cava and the MHV, in Sg8 ventral and in Sg6, after an urgent left laparoscopic hemicolectomy for an obstructing carcinoma. A laparoscopic Sg1 resection extended to Sg8 ventral were planned after neoadjuvant chemotherapy. Estimated future liver remnant (FLR) was 75% (840 ml) of healthy liver (Fig. 1). In case of right hepatectomy extended to Sg1, estimated FLR was 25% (280 ml) of healthy liver. Fig. 1 3D reconstruction and intraoperative images of Liver Tunnel (A) and Sg6 resection (B). Total liver volume: 1110 ml. Total resected liver volume 270 ml: Liver Tunnel 93 ml; Sg6 177 ml. Liver volumes were measured with HA3D™ technology with Medics3D software (Medics3D, Turin, Italy) RESULTS: Pneumoperitoneum is established, and four operative ports are placed. Sg1 is approached from the left, dividing the Glissonean pedicles and short hepatic veins. MHV is approached cranio-caudally from the dorsal side. The resection continues on the ventral side, according to our "Ultrasound Liver Map technique" with a cranio-caudal approach to the MHV.4 Sg8 ventral pedicles are divided and the resection completed with aid of indocyanine green negative staining. A Sg6 resection is then performed. Operative time was 480 min. Blood loss was 100 ml. The postoperative course was uneventful, and the patient was discharged on fourth postoperative day. The two parenchyma-sparing resections saved an estimated volume of 75% (840 ml) of healthy liver (Fig. 1). The estimated remnant liver volume after a right hepatectomy extended to Sg1 would have been only 25%. CONCLUSIONS: Tumors at the hepatocaval confluence involving Sg1 can be removed with the "Liver Tunnel," which can be performed with minimally invasive approach. The "Laparoscopic Liver Tunnel" pushes further the limit of minimally invasive parenchyma-sparing surgery for ill-located tumors with complex vascular relationship.
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Laparoscopia , Neoplasias Hepáticas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Hepáticas/secundário , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Veias Hepáticas/cirurgia , Veias Hepáticas/patologia , Hepatectomia/métodos , Laparoscopia/métodosRESUMO
BACKGROUND: For many tumors, radiomics provided a relevant prognostic contribution. This study tested whether the computed tomography (CT)-based textural features of intrahepatic cholangiocarcinoma (ICC) and peritumoral tissue improve the prediction of survival after resection compared with the standard clinical indices. METHODS: All consecutive patients affected by ICC who underwent hepatectomy at six high-volume centers (2009-2019) were considered for the study. The arterial and portal phases of CT performed fewer than 60 days before surgery were analyzed. A manual segmentation of the tumor was performed (Tumor-VOI). A 5-mm volume expansion then was applied to identify the peritumoral tissue (Margin-VOI). RESULTS: The study enrolled 215 patients. After a median follow-up period of 28 months, the overall survival (OS) rate was 57.0%, and the progression-free survival (PFS) rate was 34.9% at 3 years. The clinical predictive model of OS had a C-index of 0.681. The addition of radiomic features led to a progressive improvement of performances (C-index of 0.71, including the portal Tumor-VOI, C-index of 0.752 including the portal Tumor- and Margin-VOI, C-index of 0.764, including all VOIs of the portal and arterial phases). The latter model combined clinical variables (CA19-9 and tumor pattern), tumor indices (density, homogeneity), margin data (kurtosis, compacity, shape), and GLRLM indices. The model had performance equivalent to that of the postoperative clinical model including the pathology data (C-index of 0.765). The same results were observed for PFS. CONCLUSIONS: The radiomics of ICC and peritumoral tissue extracted from preoperative CT improves the prediction of survival. Both the portal and arterial phases should be considered. Radiomic and clinical data are complementary and achieve a preoperative estimation of prognosis equivalent to that achieved in the postoperative setting.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatectomia , Radiômica , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/mortalidade , Seguimentos , Hepatectomia/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodosRESUMO
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
BACKGROUND: Laparoscopic liver resection (LLR) has proved effective in the treatment of oligometastatic disease (1 or 2 colorectal liver metastases CRLM) with similar long-term outcomes and improved short-term results compared to open liver resection (OLR). Feasibility of parenchymal sparing LLR for high tumour burden diseases is largely unknown. Aim of the study was to compare short and long-term results of LLR and OLR in patients with ≥ 3 CRLM. METHODS: Patients who underwent first LR of at least two different segments for ≥ 3 CRLM between 01/2012 and 12/2021 were analysed. Propensity score nearest-neighbour 1:1 matching was based on relevant prognostic factors. RESULTS: 277 out of 673 patients fulfilled inclusion criteria (47 LLR and 230 OLR). After match two balanced groups of 47 patients with a similar mean number of CRLM (5 in LLR vs 6.5 in OLR, p = 0.170) were analysed. The rate of major hepatectomy was similar between the two group (10.6% OLR vs. 12.8% LLR). Mortality (2.1% OLR vs 0 LLR) and overall morbidity rates (34% OLR vs 23.4% LLR) were comparable. Length of stay (LOS) was shorter in the LLR group (5 vs 9 days, p = 0.001). No differences were observed in median overall (41.1 months OLR vs median not reached LLR) and disease-free survival (18.3 OLR vs 27.9 months LLR). CONCLUSION: Laparoscopic approach should be considered in selected patients scheduled to parenchymal sparing LR for high tumour burden disease as associated to shorter LOS and similar postoperative and long-term outcomes compared to the open approach.
Assuntos
Neoplasias Colorretais , Hepatectomia , Laparoscopia , Neoplasias Hepáticas , Pontuação de Propensão , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Carga Tumoral , Estudos Retrospectivos , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Tratamentos com Preservação do Órgão/métodosRESUMO
PURPOSE: Single large hepatocellular carcinoma >5cm (SLHCC) traditionally requires a major liver resection. Minor resections are often performed with the goal to reduce morbidity and mortality. Aim of the study was to establish if a major resection should be considered the best treatment for SLHCC or a more limited resection should be preferred. METHODS: A multicenter retrospective analysis of the HE.RC.O.LE.S. Group register was performed. All collected patients with surgically treated SLHCC were divided in 5 groups of treatment (major hepatectomy, sectorectomy, left lateral sectionectomy, segmentectomy, non-anatomical resection) and compared for baseline characteristics, short and long-term results. A propensity-score weighted analysis was performed. RESULTS: 535 patients were enrolled in the study. Major resection was associated with significantly increased major complications compared to left lateral sectionanectomy, segmentectomy and non-anatomical resection (all p<0.05) and borderline significant increased major complications compared to sectorectomy (p=0.08). Left lateral sectionectomy showed better overall survival compared to major resection (p=0.02), while other groups of treatment resulted similar to major hepatectomy group for the same item. Absence of oncological benefit after major resection and similar outcomes among the 5 groups of treatment was confirmed even in the sub-population excluding patients with macrovascular invasion. CONCLUSION: Major resection was associated to increased major post-operative morbidity without long-term survival benefit; when technically feasible and oncologically adequate, minor resections should be preferred for the surgical treatment of SLHCC.
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Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Pontuação de Propensão , Humanos , Hepatectomia/métodos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Taxa de Sobrevida , AdultoRESUMO
OBJECTIVE: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). BACKGROUND: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. MATERIAL AND METHODS: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. RESULTS: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival. CONCLUSIONS: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.
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Carcinoma Hepatocelular , Laparoscopia , Falência Hepática , Neoplasias Hepáticas , Síndrome Metabólica , Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Ascite/complicações , Ascite/cirurgia , Síndrome Metabólica/complicações , Síndrome Metabólica/cirurgia , Hepatectomia , Pontuação de Propensão , Falência Hepática/cirurgia , Tempo de Internação , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
AIM: Textbook outcome (TO) is a new surgical quality measure that combines structure, process and surgical outcomes into a single element. Our study aimed to determine the incidence of TO after simultaneous rectal and liver surgery and to use the achievement of TO as a tool to identify the best candidates for these complex procedures. METHODS: In total, 256 patients who underwent simultaneous liver and rectal surgery for Stage IV rectal cancer between January 2004 and August 2019 at five tertiary centres were enrolled. TO was defined as a lack of complication, prolonged length of stay, readmission and death. RESULTS: Mortality rate at 90 days and major morbidity rate were 2.3% and 15.6%, respectively. An overall TO was achieved in 59% of the patients, which is associated with significantly improved overall (median TO 86.3 months vs. no TO 37.4 months) and disease-free (median TO 70.6 months vs. no TO 24.9 months) survival. On multivariate analysis the presence of multi-comorbidities (OR 3.073) was associated with a reduced likelihood of achieving TO. Left lateral sectionectomy/limited resection was a protective factor (OR 0.416). CONCLUSION: TO was achieved in six of 10 patients undergoing simultaneous resections for rectal cancer and liver metastases. Achieving a TO is strongly associated with improved long-term survival. The best candidates for these procedures were patients without multiple comorbidities and those treated with left lateral sectionectomy/limited resection.
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Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Neoplasias Colorretais/cirurgia , Hepatectomia/métodos , Humanos , Incidência , Fígado/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: The difficulty of laparoscopic right liver resections (LRLR) is mainly associated with their poor accessibility. Anthropometric data rather than BMI was reported to predict transection time and blood loss. Aim of the study was to evaluate the correlation between anthropometric data and preparatory manoeuvres difficulties during LRLR. METHODS: All patients who underwent LRLR requiring full right liver mobilization from November 2019 to March 2021 were prospectively included in the study. Data on surgeons' difficulty perceptions on liver mobilization (LM), isolation of right hepatic vein (RHVI), liver manageability and visibility were rated with a 5-point scale. Data on cranio-caudal liver diameters (CCliv), CHALLENGE Index (CCliv/latero-lateral abdomen diameter), times needed to LM and RHVI were collected. RESULTS: Sixty-five patients (29 wedge and 36 anatomical resections) with a median BMI of 25.5 were analysed. One patient required open conversion due to oncological reason. No correlations between BMI and CCliv or CHALLENGE Index were found. Larger CCliv diameter correlated with longer time for both RHVI (r = 0.589, p = 0.002) and LM (r = 0.222, p = 0.049). Higher CHALLENGE index correlated with longer time for RHVI (r = 0.589, p = 0.002). The CHALLENGE index showed a linear correlation with difficulty to the isolation of RHV (r = 0.327, p = 0.045), whilst the liver manipulation difficulty increased with latero-lateral liver diameter (r = 0.244, p = 0.033). BMI had no correlation with the duration of preparatory maneuvers neither with surgeons' difficulties. CONCLUSIONS: Anthropometric data can help to anticipate the difficulty of preparatory maneuvers during laparoscopic right liver resections.
Assuntos
Laparoscopia , Neoplasias Hepáticas , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined. METHODS: Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care (ABC) method was employed to identify the benchmarks. The outcomes assessed were the rate of complications, major comorbidities, post-operative ascites (POA), post-hepatectomy liver failure (PHLF), 90-day mortality. Benchmarking was stratified for surgical complexity (CP1, CP2 and CP3). RESULTS: A total of 978 of 2698 patients fulfilled the inclusion criteria. 431 (44.1%) patients were treated with CP1 procedures, 239 (24.4%) with CP2 and 308 (31.5%) with CP3 procedures. Patients submitted to CP1 had a worse underlying liver function, while the tumor burden was more severe in CP3 cases. The ABC for complications (13.1%, 19.2% and 28.1% for CP1, CP2 and CP3 respectively), major complications (7.6%, 11.1%, 12.5%) and 90-day mortality (0%, 3.3%, 3.6%) increased with the surgical difficulty, but not POA (4.4%, 3.3% and 2.6% respectively) and PHLF (0% for all groups). CONCLUSION: We propose benchmarks for open liver resections in HCC cirrhotic patients, stratified for surgical complexity. The difference between the benchmark values and the results obtained during everyday practice reflects the room for potential growth, with the aim to encourage constant improvement among liver surgeons.
Assuntos
Carcinoma Hepatocelular , Falência Hepática , Neoplasias Hepáticas , Benchmarking , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Falência Hepática/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
Colorectal cancer is the third most common cancer worldwide, with 1.2 million patients diagnosed annually. In late-stage colorectal cancer, the most commonly used targeted therapies are the monoclonal antibodies cetuximab and panitumumab, which prevent epidermal growth factor receptor (EGFR) activation. Recent studies have identified alterations in KRAS and other genes as likely mechanisms of primary and secondary resistance to anti-EGFR antibody therapy. Despite these efforts, additional mechanisms of resistance to EGFR blockade are thought to be present in colorectal cancer and little is known about determinants of sensitivity to this therapy. To examine the effect of somatic genetic changes in colorectal cancer on response to anti-EGFR antibody therapy, here we perform complete exome sequence and copy number analyses of 129 patient-derived tumour grafts and targeted genomic analyses of 55 patient tumours, all of which were KRAS wild-type. We analysed the response of tumours to anti-EGFR antibody blockade in tumour graft models and in clinical settings and functionally linked therapeutic responses to mutational data. In addition to previously identified genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary resistance to this therapy. Novel alterations in the ectodomain of EGFR were identified in patients with acquired resistance to EGFR blockade. Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumours with increased sensitivity to anti-EGFR therapy. Therapeutic resistance to EGFR blockade could be overcome in tumour graft models through combinatorial therapies targeting actionable genes. These analyses provide a systematic approach to evaluating response to targeted therapies in human cancer, highlight new mechanisms of responsiveness to anti-EGFR therapies, and delineate new avenues for intervention in managing colorectal cancer.
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Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Genoma Humano/genética , Genômica , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Neoplasias Colorretais/metabolismo , Variações do Número de Cópias de DNA/genética , Receptores ErbB/química , Receptores ErbB/genética , Exoma/genética , Feminino , Humanos , Proteínas Substratos do Receptor de Insulina/genética , MAP Quinase Quinase 1/genética , Camundongos , Terapia de Alvo Molecular , Mutação/genética , Panitumumabe , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor ErbB-2/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Laparoscopic segment 7 segmentectomy and segment 6-7 bisegmentectomy are challenging resections because of the posterior position and the lack of landmarks. The anatomy of the right posterior Glissonean pedicle and the caudal view of laparoscopy make such resections suitable for the Glissonean pedicle-first approach. METHODS: The study population included all consecutive patients treated with laparoscopic liver resection from August 2019 to February 2020. The approach is based on the ultrasonographic identification of the right posterior or segmental pedicle from the dorsal side of the liver after complete mobilization. The pedicle of interest is isolated through mini-hepatotomy and clamped. The segment anatomy is defined by ischemia. The transection starts from the ventral side, close to the right hepatic vein that is exposed and followed craniocaudally. RESULTS: Ten patients underwent anatomical laparoscopic resection of right posterolateral segments. There were 7 colorectal liver metastases, 2 hepatocellular carcinoma, and 1 biliary cysto-adenoma. Five patients underwent Sg7 resection, one patient underwent a Sg7 subsegmentectomy, and 4 underwent Sg6-7 bisegmentectomy. The Glissonean pedicle-first approach was feasible in eight patients. The craniocaudal approach to the RHV was feasible in six patients, not indicated in three cases and was abandoned in one patient for technical difficulty. There was no operative morbidity or mortality. Median post-operative hospital stay was 5 days. CONCLUSIONS: The Glissonean pedicle-first approach is safe and effective for laparoscopic anatomic resections of the right posterior sector. The craniocaudal approach to right hepatic vein from the ventral side is a convenient procedure to follow the segmental anatomy deep in the parenchyma.
Assuntos
Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/cirurgia , Feminino , Veias Hepáticas/cirurgia , Humanos , Tempo de Internação , Fígado/anatomia & histologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Duração da CirurgiaRESUMO
BACKGROUND: Intraoperative liver ultrasound appears superior to liver-specific contrast-enhanced magnetic resonance imaging (MRI) to stage colorectal liver metastases (CRLMs). Most of the data come from studies on open surgery. Laparoscopic ultrasound (LUS) is technically demanding and its reliability is poor investigated. Aim of the study was to assess the accuracy of LUS staging for CRLMs compared to MRI. METHODS: All patients with CRLMs scheduled for laparoscopic liver resection (LLR) between 01/2010 and 06/2019 who underwent preoperative MRI were considered for the study. LUS and MRI performance was compared on a patient by patient basis. Reference standards were final pathology and 6 months follow-up results. RESULTS: Amongst 189 LLR for CRLMs, 146 met inclusion criteria. Overall, 391 CRLMs were preoperatively detected by MRI. 24 new nodules in 16 (10.9%) patients were found by LUS and resected. Median diameter of new nodules was 5.5 mm (2-10 mm) and 10 (41.6%) were located in the hepatic dome. Pathology confirmed 17 newly detected malignant nodules (median size 4 mm) in 11 (7.5%) patients. Relationships between intrahepatic vessels and tumours differed between LUS and MRI in 9 patients (6.1%). Intraoperative surgical strategy changed according LUS findings in 19 (13%) patients, requiring conversion to open approach in 3 (15.8%) of them. The sensitivity of LUS was superior to MRI (93.1% vs 85.6% whilst specificity was similar (98.6% MRI vs 96.5% LUS). CONCLUSIONS: Laparoscopic liver ultrasound improves liver staging for CRLMs compared to liver-specific MRI.
Assuntos
Neoplasias Colorretais , Laparoscopia , Neoplasias Hepáticas , Neoplasias Colorretais/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The high technical difficulty of using a laparoscopic approach to reach the posterosuperior liver segments is mainly associated with their poor accessibility. This study was performed to analyze correlations between anthropometric data and intraoperative outcomes. STUDY DESIGN: All patients who underwent segmentectomy or wedge laparoscopic liver resection (LLR) of segments seven and/or eight from June 2012 to November 2019 were retrospectively analyzed. The exclusion criteria were intrahepatic cholangiocarcinoma, associated resection, multiple concomitant LLR, redo resection, and lack of preoperative imaging. Anthropometric data were correlated with intraoperative outcomes. RESULTS: Forty-one patients (wedge resection, n = 32; segmentectomy, n = 9) were analyzed. A strong correlation was found between the craniocaudal liver diameter (CCliv) and liver volume (r = 0.655, p < 0.001). The anteroposterior liver diameter was moderately correlated with both the laterolateral abdominal diameter (LLabd) (r = 0.372, p = 0.008) and anteroposterior abdominal diameter (r = 0.371, p = 0.008). The body mass index (BMI) was not correlated with liver diameters. Women had a longer CCliv (p = 0.002) and shorter LLabd (p < 0.001) than men. The liver and abdominal measurements were combined to reduce this sex-related disparity. The CCliv/LLabd ratio (CHALLENGE index) was significantly correlated with the time of transection (r = 0.382, p = 0.037) and blood loss (r = 0.352, p = 0.029). The association between the CHALLENGE index and intraoperative blood loss was even stronger when considering only anatomical resection (r = 0.577, p = 0.048). A CHALLENGE index of > 0.4 (area under the curve, 0.757; p = 0.046) indicated a higher bleeding risk. The BMI predicted no intraoperative outcomes. CONCLUSION: Anthropometric data rather than the BMI can help anticipate the difficulty of LLR of segments seven and eight.
Assuntos
Laparoscopia , Neoplasias Hepáticas , Feminino , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Masculino , Duração da Cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: and purpose: FDG-PET/CT has gained acceptance for tumours staging. Few and conflicting data exist on the sensitivity of FDG-PET/CT in identifying colorectal mucinous liver metastases (mucCRLM). The aim of this study was to evaluate the diagnostic performance of the FDG-PET/CT in patients with mucCRLM who underwent liver surgery. METHODS: All patients affected by mucCRLM scheduled for liver resection who had undergone preoperative FDG-PET/CT between 2005 and 2018 were analyzed. Diagnostic performance of FDG-PET/CT was assessed in organ and lesion-based analysis. RESULTS: 58 patients out of 131 (44.2%) affected by mucCRLM fulfilled the inclusion criteria. 118 mucCRLM were detected. FDG-PET/CT confirmed 71 (60.2%) CRLM in 51 patients. The sensitivity and specificity of FDG-PET/CT were 89.4% and 100% in the organ-based analysis and 60.7% and 100% in lesion-based analysis. Absence of micro-vascular invasion (100% vs. 23%, p < 0.001) and median percentage of viable tumour cells were associated with FDG-PET/CT false negative (15% vs. 60%, p = 0.007). At ROC analysis viable tumour cells percentage >25% was associated with low risk of false negative (AUC 0.848; p = 0.006). CONCLUSIONS: FDG-PET/CT had a significant rate of false negative results in patients with mucinous colorectal liver metastases. Negative FDG-PET/CT in patients with low percentage of viable tumour cells after chemotherapy should be considered with caution.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Fluordesoxiglucose F18 , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Difficulty scores (DSs) have been proposed to rate laparoscopic liver resection (LLR) technical difficulty increasing surgical safety. The aim of the study was to validate three DSs (Hasegawa, Halls and Kawaguchi) and compare their ability to predict technical difficulty and postoperative outcomes. MATERIALS AND METHODS: All patients who underwent LLR from January 2006 to January 2019 were analyzed. Exclusion criteria were cyst fenestrations, thermal ablation, missing data for the computation of the DS and a follow-up < 90 days. RESULTS: The population comprised 300 patients. The DS distribution in the study population was: Halls low 55 (18.3%), moderate 82 (27.3%), high 111 (37%) and extremely high 52 (17.3%); Hasegawa low 130 (43.3%), medium 105 (35%) and high 65 (21.7%); Kawaguchi Grade I 194 (64.7%), Grade II 47 (15.7%) and Grade III 59 (19.7%). Hasegawa and Kawaguchi showed the strongest correlation (r = 0.798, p < 0.001). Technical complexity, evaluated using the Pringle maneuver, Pringle time, blood loss and operative time, increased significantly with Hasegawa and Kawaguchi score classes (p < 0.001 for all comparisons). None of the scores properly stratified postoperative complications. The highest Kawaguchi (23.7% grade III vs. 13.7% grades I and II, p = 0.057) and Hasegawa (24.6% high vs. 13.2% low/medium, p = 0.025) classes had a higher overall morbidity rate than medium-low ones. CONCLUSIONS: Kawaguchi and Hasegawa scores predicted LLR's technical difficulty. None of the scores discriminated the postoperative complication risk of low classes compared with medium ones.
Assuntos
Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: To evaluate early outcomes of venous reconstruction with peritoneal patch (PP) during resection for hepatic malignancies. METHODS: Since May 2015, PP was considered as the first option for venous reconstruction in the case of lateral resection. Between May 2015 and June 2019, 579 consecutive hepatectomies for malignancies were performed at our institution. Among 27 patients requiring venous resection, PP was used in 22, who were included in the present study. Data from a prospectively collected database were analysed. RESULTS: Tumour types were ten colorectal metastases (CRLM), six intrahepatic cholangiocarcinomas, four hilar cholangiocarcinomas, one hepatocellular carcinoma and one gallbladder carcinoma. Hepatectomies were major in 50% of cases. Eleven patients had hepatic vein resections, eight portal vein and three inferior vena cava. Venous reconstruction enabled resection in 12 (54.5%) patients, otherwise non-resectable. Among CRLM, the venous reconstruction allowed avoidance of major resection in eight (80%) cases. Median operative time was 456 min (range 270-960). Blood loss was a median 300 cc (range 40-1500), and blood transfusions were required in three patients (13.6%). At pathological examination, venous infiltration was confirmed in 14 (63.6%) patients. No vascular complications related to the patch were recorded. Post-operative major (Dindo III/IV) complications were observed in two (9%) patients. One patient died because of liver failure without vascular thrombosis and one due to biliary fistula complicated by arterial bleeding. Overall, post-operative mortality was 9% (2/22). CONCLUSIONS: Venous reconstruction with peritoneal patch during hepatectomy for malignancies can feasibly allow resection in otherwise unresectable patients and decrease the rate of major resection in colorectal liver metastases.
Assuntos
Hepatectomia/métodos , Veias Hepáticas/cirurgia , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Veia Cava Inferior/cirurgia , Adulto , Idoso , Neoplasias dos Ductos Biliares/irrigação sanguínea , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/irrigação sanguínea , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirurgia , Feminino , Neoplasias da Vesícula Biliar/irrigação sanguínea , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Procedimentos de Cirurgia Plástica/métodos , UltrassonografiaRESUMO
BACKGROUND: Several studies have described a worse prognosis for right-sided colon cancer compared to left-sided. The aim of this study was to compare patterns of recurrence and survival following resection of liver metastases (LM) from right-sided (RS) versus left-sided (LS) colon cancer. METHODS: Patients undergoing resection for colon cancer LM between 2000 and 2017 were analyzed. Rectal cancer, multiple primaries and unknown location were excluded. RESULTS: Out of 995 patients, 686 fulfilled inclusion criteria (RS-LM = 322, LS-LM = 364). RS colon cancer had higher prevalence of metastatic lymph nodes (67.4% vs. 57.1%, P = 0.008). RS-LM were more often mucinous (16.8% vs. 8.5%, P = 0.001) and G3 (58.3% vs. 48.9%, P = 0.014). 451 (65.7%) patients experienced recurrence (RS-LM 68.9% vs. LS-LM 62.9%). In RS-LM group, recurrence was more often encephalic (2.3% vs. 0%, P = 0.029) and at multiple sites (34.2% vs. 23.5%, P = 0.012). The rate of re-resection was lower in RS-LM patients (27.9% vs. 37.5%, P = 0.024). Multivariate analysis showed RS-LM to have worse 5-year overall (35.8% vs. 51.2%, P = 0.002) and disease-free survival (26% vs. 43.6%, P = 0.002). CONCLUSIONS: RS-LM is associated with worse survival and aggressive recurrences, with lower chance of re-resection.
Assuntos
Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/terapia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Metastasectomia , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.