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1.
Br J Surg ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35511599

RESUMO

BACKGROUND: The aim of this study was to investigate the prognostic impact of perineural invasion (PNI) on tumour recurrence and survival among patients with resected intrahepatic cholangiocarcinoma (ICC). METHODS: This was a multicentre, retrospective study of patients who underwent resection with curative intent for ICC between 2000 and 2017. The relationship between PNI, clinicopathological characteristics, and long-term survival was analysed in the overall cohort and the subset of patients with early-stage ICC. RESULTS: Among 1095 patients who underwent resection of ICC, PNI was present in 239 (21.8 per cent). In univariable analysis, PNI was associated with worse disease-free survival (DFS) (median 13.2 versus 16.1 months for patients with and without PNI respectively; P = 0.038) and overall survival (OS) (26.4 versus 41.5 months; P < 0.001). In multivariable analysis, PNI was an independent risk factor associated with reduced DFS (hazard ratio (HR) 1.56, 95 per cent c.i. 1.06 to 2.13; P = 0.019) and OS (HR 1.74, 1.16 to 2.60; P = 0.007). In subgroup analysis of patients with early-stage disease (AJCC T1-2, 981 patients; or N0, 249 patients), PNI remained associated with worse DFS (T1-2: median 13.7 versus 16.6 months in patients with and without PNI respectively, P = 0.019; N0: 11.7 versus 17.5 months, P = 0.022) and OS (T1-2: 28.5 versus 45.7 months, P < 0.001; N0: 34.9 versus 47.5 months, P = 0.036). CONCLUSION: PNI is a strong independent predictor of tumour recurrence and long-term survival following resection of ICC with curative intent, even among patients with early-stage disease. The presence of PNI should be assessed routinely.

2.
JAMA Surg ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35544131

RESUMO

Importance: Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation. Objective: To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection. Design, Setting, and Participants: In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible. The HAIP group consisted of consecutive patients from a single center who underwent HAIP floxuridine chemotherapy for unresectable multifocal iCCA between January 1, 2001, and December 31, 2018. The resection group consisted of consecutive patients from 12 centers who underwent a curative-intent resection for multifocal iCCA between January 1, 1990, and December 31, 2017. Resectable metastatic disease to regional lymph nodes and previous systemic therapy were permitted. Patients with distant metastatic disease (ie, stage IV), those who underwent resection before starting HAIP floxuridine chemotherapy, and those who received a liver transplant were excluded. Data were analyzed on September 1, 2021. Main Outcomes and Measures: Overall survival in the 2 treatment groups was compared using the Kaplan-Meier method and log-rank test. Results: A total of 319 patients with multifocal iCCA were included: 141 in the HAIP group (median [IQR] age, 62 [53-70] years; 79 [56.0%] women) and 178 in the resection group (median [IQR] age, 60 [50-69] years; 91 [51.1%] men). The HAIP group was characterized by a higher percentage of bilobar disease (88.0% [n = 124] vs 34.3% [n = 61]), larger tumors (median, 8.4 cm vs 7.0 cm), and a higher proportion of patients with 4 or more lesions (66.7% [94] vs 24.2% [43]). Postoperative mortality after 30 days was 0.8% (95% CI, 0.0%-2.1%) in the HAIP group vs 6.2% (95% CI, 2.3%-9.7%) in the resection group (P = .01). The median OS for HAIP was 20.3 months vs 18.9 months for resection (P = .32). Five-year OS in patients with 2 or 3 lesions was 23.7% (95% CI, 12.3%-45.7%) in the HAIP group vs 25.7% (95% CI, 17.9%-37.0%) in the resection group. Five-year OS in patients with 4 or more lesions was 5.0% (95% CI, 1.7%-14.3%) in the HAIP group vs 6.8% (95% CI, 1.8%-25.3%) in the resection group. After adjustment for tumor diameter, number of tumors, and lymph node metastases, the hazard ratio of HAIP vs resection was 0.75 (95% CI, 0.55-1.03; P = .07). Conclusions and Relevance: This cohort study found that patients with multifocal iCCA had similar OS after HAIP floxuridine chemotherapy vs resection. Resection of multifocal intrahepatic cholangiocarcinoma needs to be considered carefully given the complication rate of major liver resection; HAIP floxuridine chemotherapy may be an effective alternative option.

3.
Liver Int ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533020

RESUMO

BACKGROUND: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR). METHODS: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyze the influence of demographic, tumor type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in milliliter and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula. RESULTS: A total of 734 patients were included from 99 centers. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18-0.28) and 0.39 (IQR: 0.31-0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p=0.02), height ˃1.76 m (p˂0.01), weight ˃83 kg (p˂0.01), BMI˃28 (p˂0.01), male gender (p˂0.01), antihypertensive therapy (p˂0.01), operation time ˃370 minutes (p˂0.01), and hospital stay˃14 days (p˂0.01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared to 50% of female, and female present 15.3% in group ˃14 days compared to 20.6% of male. CONCLUSION: Height, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.

6.
J Vasc Interv Radiol ; 33(5): 525-529, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35489784

RESUMO

Future liver remnant (FLR) volume is an important indicator of the risk of posthepatectomy liver failure (PHLF) and limits the feasibility of major hepatectomies. A case series of 5 patients treated with a novel approach is presented. Laparoscopic liver partitioning was combined with subsequent liver venous deprivation (embolization of both the portal and the hepatic veins). Baseline average FLR was 28.8%. All procedures were successfully performed without major complications. Mean 1-, 2- and 4-week hypertrophy of the FLR were 35%, 40.3%, and 46.4%, respectively. Four patients underwent planned surgery after a mean interval of 28 days. Of these, 2 patients achieved sufficient FLR volume and function after 2 weeks and underwent surgery before the 4-week volumetric analysis. One patient did not undergo surgery because of intraoperative diagnosis of peritoneal metastases. No cases of PHLF were observed at 5-day follow-up.


Assuntos
Laparoscopia , Falência Hepática , Neoplasias Hepáticas , Humanos , Hipertrofia/complicações , Hipertrofia/cirurgia , Laparoscopia/efeitos adversos , Falência Hepática/diagnóstico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia
7.
Artigo em Inglês | MEDLINE | ID: mdl-35305075

RESUMO

BACKGROUND/PURPOSE: Quality measures in surgery are important to establish appropriate levels of care and to develop improvement strategies. The purpose of this study was to provide risk-adjusted outcome measures after laparoscopic liver resection (LLR). METHODS: Data from a prospective, multicenter database involving 4318 patients submitted to LLRs in 41 hospitals from an intention-to-treat approach (2014-2020) were used to analyze heterogeneity (I2 ) among centers and to develop a risk-adjustment model on outcome measures through multivariable mixed-effect models to account for confounding due to case-mix. RESULTS: Involved hospitals operated on very different patients: the largest heterogeneity was observed for operating in the presence of previous abdominal surgery (I2 :79.1%), in cirrhotic patients (I2 :89.3%) suffering from hepatocellular carcinoma (I2 :88.6%) or requiring associated intestinal resections (I2 :82.8%) and in regard to technical complexity (I2 for the most complex LLRs: 84.1%). These aspects determined substantial or large heterogeneity in overall morbidity (I2 :84.9%), in prolonged in-hospital stay (I2 :86.9%) and in conversion rate (I2 :73.4%). Major complication had medium heterogeneity (I2 :46.5%). The heterogeneity of mortality was null. Risk-adjustment accounted for all of this variability and the final risk-standardized conversion rate was 8.9%, overall morbidity was 22.1%, major morbidity was 5.1% and prolonged in-hospital stay was 26.0%. There were no outliers among the 41 participating centers. An online tool was provided. CONCLUSIONS: A benchmark for LLRs including all eligible patients was provided, suggesting that surgeons can act accordingly in the interest of the patient, modifying their approach in relation to different indications and different experience, but finally providing the same quality of care.

8.
HPB (Oxford) ; 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35293320

RESUMO

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.

9.
Chirurgia (Bucur) ; 117(1): 110-113, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35272761

RESUMO

The magnification of images provided by minimally-invasive surgery (MIS) allows a very sharp and precise dissection of the hepatic hilum, allowing to overcome the technical complexity of surgery of perihilar cholangiocarcinoma (PHC). Recently, the feasibility and reproducibility of MIS for PHC are reported: within centers with adequate expertise and respecting the cornerstones of oncological adequacy, it provides short term advantages in a selected population of patients. The video reports the case of a patient with PHC involving the right biliary duct and requiring right hepatectomy with biliary confluence and segment 1 resection, with associated lymphadenectomy. Current evidences, together with feasibility and reproducibility of the technique shown in this video, appear promising and constitute a good prerequisite for the further implementation of this approach to improve patients outcome while following the principles of surgical oncology in hilar cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Humanos , Tumor de Klatskin/cirurgia , Reprodutibilidade dos Testes , Resultado do Tratamento
10.
Ann Surg Oncol ; 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35298762

RESUMO

BACKGROUND: The prognostic impact of tumor necrosis among patients undergoing resection for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. METHODS: Patients who underwent curative-intent resection for ICC between 2000 and 2017 were identified using a multi-institutional database. The association of pathologic tumor necrosis with overall survival (OS) and recurrence-free survival (RFS) was examined. RESULTS: Among 757 patients who underwent resection for ICC, tumor necrosis was present in 384 (50.7%) patients (no necrosis: n = 373, 49.3%; <50% necrosis: n = 291, 38.4%; ≥50% necrosis: n = 93, 12.3%). Tumor necrosis was associated with worse OS (5-year OS: no necrosis 39.3% vs. <50% necrosis 34.7% and ≥50% necrosis 24.0%; p = 0.03) and RFS (5-year RFS: no necrosis 25.7% vs. <50% necrosis 13.9% and ≥50% necrosis 18.8%; p < 0.001). After stratifying by T stage, tumor necrosis was able to further stratify prognosis among patients with T1a ICC (5-year RFS: T1a and no necrosis 46.7% vs. T1a and necrosis 36.1%; p = 0.02), and T1b ICC (5-year RFS: T1b and no necrosis 31.1% vs. T1b and necrosis 11.2%; p = 0.006), but was not associated with outcomes among patients with more advanced T2-T3 disease. Patients with T1a ICC and tumor necrosis had similar 5-year RFS as individuals with T1b ICC and no tumor necrosis (36.1% vs. 31.1%; p = 0.66). CONCLUSION: Tumor necrosis was associated with worse prognosis among patients with T1 ICC. Tumor necrosis for T1 ICC should be considered as an important factor to further stratify outcomes of patients with early T-stage ICC.

11.
Trials ; 23(1): 206, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264216

RESUMO

BACKGROUND: A shift towards parenchymal-sparing liver resections in open and laparoscopic surgery emerged in the last few years. Laparoscopic liver resection is technically feasible and safe, and consensus guidelines acknowledge the laparoscopic approach in the posterosuperior segments. Lesions situated in these segments are considered the most challenging for the laparoscopic approach. The aim of this trial is to compare the postoperative time to functional recovery, complications, oncological safety, quality of life, survival and costs after laparoscopic versus open parenchymal-sparing liver resections in the posterosuperior liver segments within an enhanced recovery setting. METHODS: The ORANGE Segments trial is an international multicentre randomised controlled superiority trial conducted in centres experienced in laparoscopic liver resection. Eligible patients for minor resections in the posterosuperior segments will be randomised in a 1:1 ratio to undergo laparoscopic or open resections in an enhanced recovery setting. Patients and ward personnel are blinded to the treatment allocation until postoperative day 4 using a large abdominal dressing. The primary endpoint is time to functional recovery. Secondary endpoints include intraoperative outcomes, length of stay, resection margin, postoperative complications, 90-day mortality, time to adjuvant chemotherapy initiation, quality of life and overall survival. Laparoscopic liver surgery of the posterosuperior segments is hypothesised to reduce time to functional recovery by 2 days in comparison with open surgery. With a power of 80% and alpha of 0.04 to adjust for interim analysis halfway the trial, a total of 250 patients are required to be randomised. DISCUSSION: The ORANGE Segments trial is the first multicentre international randomised controlled study to compare short- and long-term surgical and oncological outcomes of laparoscopic and open resections in the posterosuperior segments within an enhanced recovery programme. TRIAL REGISTRATION: ClinicalTrials.gov NCT03270917 . Registered on September 1, 2017. Before start of inclusion. PROTOCOL VERSION: version 12, May 9, 2017.


Assuntos
Hepatectomia , Laparoscopia , Neoplasias Hepáticas , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
J Am Coll Surg ; 234(2): 99-112, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35213428

RESUMO

BACKGROUND: Despite many developments, postoperative bile leakage (POBL) remains a relatively common postoperative complication after laparoscopic liver resection (LLR) and open liver resection (OLR). This study aimed to assess the incidence and clinical impact of POBL in patients undergoing LLR and OLR in a large international multicenter cohort using a propensity score-matched analysis. STUDY DESIGN: Patients undergoing LLR or OLR for all indications between January 2000 and October 2019 were retrospectively analyzed using a large, international, multicenter liver database including data from 15 tertiary referral centers. Primary outcome was clinically relevant POBL (CR-POBL), defined as Grade B/C POBL. RESULTS: Overall, 13,379 patients met the inclusion criteria and were included in the analysis (6,369 LLR and 7,010 OLR), with 6.0% POBL. After propensity score matching, a total of 3,563 LLR patients were matched to 3,563 OLR patients. In both groups, propensity score matching accounted for similar extent and types of resections. The incidence of CR-POBL was significantly lower in patients after LLR as compared with patients after OLR (2.6% vs 6.0%; p < 0.001). Among the subgroup of patients with CR-POBL, patients after LLR experienced less severe (non-POBL) postoperative complications (10.1% vs 20.9%; p = 0.028), a shorter hospital stay (12.5 vs 17 days; p = 0.001), and a lower 90-day/in-hospital mortality (0% vs 5.4%; p = 0.027) as compared with patients after OLR with CR-POBL. CONCLUSION: Patients after LLR seem to experience a lower rate of CR-POBL as compared with the open approach. Our findings suggest that in patients after LLR, the clinical impact of CR-POBL is less than after OLR.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Bile , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Incidência , Laparoscopia/efeitos adversos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de Propensão , Estudos Retrospectivos
14.
HPB (Oxford) ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35125292

RESUMO

BACKGROUND: We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments. METHODS: Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments). RESULTS: 2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS. CONCLUSION: SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.

15.
J Chemother ; : 1-7, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35156913

RESUMO

Biliary tract cancer's (BTC) treatment main stone for advanced stages is constituted by chemotherapy. Surgical centralization and physicians' confidence in the use of new technologies and molecular analysis turned out to be of interest and potentially influencing survival. After applying a random-effect model, the relationship between each clinical variable on the main outcome was investigated through multilevel mixed-effects logistic regression. The risk-standardized outcomes were calculated for each centre involved. In the unadjusted cohort the median survival was 8.6 months (95%C.I.: 7.8-9.3) with a 9-month survival rate of 48.3% (95%C.I.: 45.0-51.5). A substantial heterogeneity across hospitals was found (I2: 70.3%). In multilevel mixed effect logistic regression, male, being treated for gallbladder cancer, higher ECOG, increased NLR, CEA and Ca 19.9 and low value of haemoglobin showed to increase the odds for 9-month mortality. The model estimated that the residual variance observed in 9-month mortality was attributable for the 2.6% to the treating hospital. Through a multilevel mixed effect model, average risk-standardized mortality within 9 months was 50.1%. As noticeable, all hospital's risk-standardized mortality falls within 95%C.I., thus all participating centres provided similar outcomes when adjusted for patient case-mix. Heterogenicity between hospital did not affect the outcome in term of overall survival.

16.
Updates Surg ; 74(2): 535-545, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35099776

RESUMO

Surgery has been the mainstay treatment for colorectal liver metastases (CRLM). Although the benefits of a laparoscopic approach have been evidenced by several comparative studies, the comparison between robotic and laparoscopic liver surgery has not been elucidated. Thus, in this study, we aim to analyze the short-term outcomes of a multicenter population that underwent robotic versus laparoscopic liver resection for CRLM. Consecutive patients with CRLM who were enrolled in the IGoMILS registry between November 2014 and June 2019 were retrospectively evaluated to compare robot-assisted procedures with laparoscopic procedures. Primary outcomes were postoperative morbidity and mortality, while secondary outcomes were length of hospital stay, operative time, and histological features of the surgical specimen. The effect size of surgical technique on resection margins was quantified using Hedges' g. In total, 1030 patients underwent minimally invasive liver surgery (MILS) for CRLM; of these, 77 (7.5%) underwent a robot-assisted approach (R-MILS), whereas 953 (92.5%) underwent a laparoscopic approach (L-MILS). Laparoscopy and robot-assisted surgery were comparable in terms of postoperative outcomes: specifically, complication rates, Comprehensive Complication Index (CCI®), intraoperative blood loss, conversion rate, operative time, and length of hospital stay did not differ significantly between the two groups. R-MILS showed a reduced rate of R1 resection margins (19.9 vs. 28.8%, p = 0.025) and wider surgical margins compared with L-MILS (8 vs. 3 mm, p < 0.001). The effect size of robot-assisted surgery was increased for posterosuperior lesions (g = 0.78) and difficult procedures (g = 1.92). As per our findings, it was determined that robot-assisted liver surgery offers some technical advantages over conventional laparoscopy, maintaining the benefits of minimally invasive surgery on short-term outcomes.


Assuntos
Neoplasias Colorretais , Laparoscopia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Neoplasias Colorretais/cirurgia , Humanos , Tempo de Internação , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento
17.
Eur Radiol ; 32(6): 4147-4159, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35092474

RESUMO

OBJECTIVES: Oligometastatic colorectal cancer benefits of locoregional treatments but data concerning microwave ablation (MWA) are limited and interactions with systemic therapy are still debated. The aim of this study is to evaluate safety and effectiveness of Thermosphere™ MWA (T-MWA) of colorectal liver metastases (CLM) and factors affecting local tumor progression-free survival (LTPFS). METHODS: In this multi-institutional retrospective study (January 2015-September 2019), patients who underwent T-MWA for CLM were enrolled. Complications according to SIR classification were collected, primary efficacy and LTP were calculated. Analyzed variables included CLM size at diagnosis and at ablation, CLM number, ablation margins, intra-segment progression, chemotherapy before ablation (CBA), variations in size (ΔSDIA-ABL), and velocity of size variation (VDIA-ABL) between CLM diagnosis and ablation. Uni/multivariate analyses were performed using mixed effects Cox model to account for the hierarchical structure of data, patient/lesions. RESULTS: One hundred thirty-two patients with 213 CLM were evaluated. Complications were reported in 6/150 procedures (4%); no biliary complications occurred. Primary efficacy was achieved in 204/213 CLM (95.7%). LTP occurred in 58/204 CLM (28.4%). Six-, twelve-, and eighteen-month LTPFS were 88.2%, 75.8%, and 69.9%, respectively. At multivariate analysis, CLM size at ablation (p = 0.00045), CLM number (p = 0.046), ablation margin < 5 mm (p = 0.0035), and intra-segment progression (p < 0.0001) were statistically significant for LTPFS. ΔSDIA-ABL (p = 0.63) and VDIA-ABL (p = 0.38) did not affect LTPFS. Ablation margins in the chemo-naïve group were larger than those in the CBA group (p < 0.0001). CONCLUSION: T-MWA is a safe and effective technology with adequate LTPFS rates. Intra-segment progression is significantly linked to LTPFS. CBA does not affect LTPFS. Anticipating ablation before chemotherapy may take the advantages of adequate tumor size with correct ablation margin planning. KEY POINTS: • Thermosphere™-Microwave ablation is a safe and effective treatment for colorectal liver metastases with no registered biliary complications in more than 200 ablations. • Metastases size at time of ablation, intra-segment progression, and minimal ablation margin < 5 mm were found statistically significant for local tumor progression-free survival. • Chemotherapy before ablation modifies kinetics growth of the lesions but deteriorates ablation margins and does not significantly impact local tumor progression-free survival.


Assuntos
Ablação por Cateter , Neoplasias Colorretais , Neoplasias Hepáticas , Ablação por Radiofrequência , Ablação por Cateter/métodos , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
18.
Ann Surg ; 275(4): 743-752, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35081572

RESUMO

OBJECTIVE: The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario. BACKGROUND DATA: The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. METHODS: BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups. RESULTS: Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. Eastern Cooperative Oncological Group Performance Status (ECOG-PS), presence of cirrhosis, steatosis, Child-Pugh grade, hepatitis B virus and hepatitis C virus, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG = 374 and SOR = 263. After IPW, 1-3-5 years OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (P < 0.001). Similar trends were observed after subgrouping patients by ECOG-PS = 0 and ECOG-PS >0, and by the intrahepatic location of portal vein invasion. At Cox regression, sorafenib treatment (hazard ratio 4.436; 95% confidence interval 3.19-6.15; P < 0.001) and Charlson Index (hazard ratio 1.162; 95% confidence interval 1.06-1.27; P = 0.010) were the only independent predictors of mortality. PFS at 1-3-5 years were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (P = 0.007). CONCLUSIONS: In BCLC C patients without extrahepatic spread but with intrahepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estadiamento de Neoplasias , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Estudos Retrospectivos , Sorafenibe/uso terapêutico , Resultado do Tratamento
20.
Nat Biotechnol ; 40(2): 235-244, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34635836

RESUMO

Recent efforts have succeeded in surveying open chromatin at the single-cell level, but high-throughput, single-cell assessment of heterochromatin and its underlying genomic determinants remains challenging. We engineered a hybrid transposase including the chromodomain (CD) of the heterochromatin protein-1α (HP-1α), which is involved in heterochromatin assembly and maintenance through its binding to trimethylation of the lysine 9 on histone 3 (H3K9me3), and developed a single-cell method, single-cell genome and epigenome by transposases sequencing (scGET-seq), that, unlike single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq), comprehensively probes both open and closed chromatin and concomitantly records the underlying genomic sequences. We tested scGET-seq in cancer-derived organoids and human-derived xenograft (PDX) models and identified genetic events and plasticity-driven mechanisms contributing to cancer drug resistance. Next, building upon the differential enrichment of closed and open chromatin, we devised a method, Chromatin Velocity, that identifies the trajectories of epigenetic modifications at the single-cell level. Chromatin Velocity uncovered paths of epigenetic reorganization during stem cell reprogramming and identified key transcription factors driving these developmental processes. scGET-seq reveals the dynamics of genomic and epigenetic landscapes underlying any cellular processes.


Assuntos
Eucromatina , Heterocromatina , Cromatina/genética , Epigênese Genética/genética , Eucromatina/genética , Heterocromatina/genética , Humanos , Transposases/genética
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