RESUMO
In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence.
RESUMO
BACKGROUND: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single-photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection. METHODS: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose-limiting toxicities were assessed 6-8 weeks and 6 months after completing radiotherapy. RESULTS: All 12 patients had colorectal liver metastases and received prior hepatotoxic chemotherapy; 8 patients underwent prior liver resection. Median computed tomography anatomical nontumor liver volume was 1584 cc (range = 764-2699 cc). Median SPECT functional liver volume was 1117 cc (range = 570-1928 cc). Median nontarget computed tomography and SPECT liver volumes below the volumetric dose constraint were 997 cc (range = 544-1576 cc) and 684 cc (range = 429-1244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No dose-limiting toxicities were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%. CONCLUSION: Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process, which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function. TRIAL REGISTRATION: NCT02626312.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Fígado , Radioterapia Guiada por Imagem , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Masculino , Feminino , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Radioterapia Guiada por Imagem/métodos , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/diagnóstico por imagem , Tamanho do Órgão , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Planejamento da Radioterapia Assistida por Computador/métodos , AdultoAssuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Mutação , Terapia Neoadjuvante/métodos , Hepatectomia/métodos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Feminino , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Portal vein embolization with stem cell augmentation (PVESA) is an emerging approach for enhancing the growth of the liver segment that will remain after surgery (i.e., future liver remnant, FLR) in patients with liver cancer. Conventional portal vein embolization (PVE) aims to induce preoperative FLR growth, but it has a risk of failure in patients with underlying liver dysfunction and comorbid illnesses. PVESA combines PVE with stem cell therapy to potentially improve FLR size and function more effectively and efficiently. Various types of stem cells can help improve liver growth by secreting paracrine signals for hepatocyte growth or by transforming into hepatocytes. Mesenchymal stem cells (MSCs), unrestricted somatic stem cells, and small hepatocyte-like progenitor cells have been used to augment liver growth in preclinical animal models, while clinical studies have demonstrated the benefit of CD133 + bone marrow-derived MSCs and hematopoietic stem cells. These investigations have shown that PVESA is generally safe and enhances liver growth after PVE. However, optimizing the selection, collection, and application of stem cells remains crucial to maximize benefits and minimize risks. Additionally, advanced stem cell technologies, such as priming, genetic modification, and extracellular vesicle-based therapy, that could further enhance efficacy outcomes should be evaluated. Despite its potential, PVESA requires more investigations, particularly mechanistic studies that involve orthotopic animal models of liver cancer with concomitant liver injury as well as larger human trials.
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Embolização Terapêutica , Veia Porta , Humanos , Embolização Terapêutica/métodos , Animais , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Regeneração Hepática , Fígado/patologia , Transplante de Células-Tronco , Células-Tronco Mesenquimais/citologiaAssuntos
Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Margens de Excisão , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
BACKGROUND: For liver volumetry, manual tracing on computed tomography (CT) images is time-consuming and operator dependent. To overcome these disadvantages, several three-dimensional simulation software programs have been developed; however, their efficacy has not fully been evaluated. METHODS: Three physicians performed liver volumetry on preoperative CT images on 30 patients who underwent formal right hepatectomy, using manual tracing volumetry and two simulation software programs, SYNAPSE and syngo.via. The future liver remnant (FLR) was calculated using each method of volumetry. The primary endpoint was reproducibility and secondary outcomes were calculation time and learning curve. RESULTS: The mean FLR was significantly lower for manual volumetry than for SYNAPSE or syngo.via; there was no significant difference in mean FLR between the two software-based methods. Reproducibility was lower for the manual method than for the software-based methods. Mean calculation time was shortest for SYNAPSE. For the two physicians unfamiliar with the software, no obvious learning curve was observed for using SYNAPSE, whereas learning curves were observed for using syngo.via. CONCLUSIONS: Liver volumetry was more reproducible and faster with three-dimensional simulation software, especially SYNAPSE software, than with the conventional manual tracing method. Software can help even inexperienced physicians learn quickly how to perform liver volumetry.
Assuntos
Hepatectomia , Imageamento Tridimensional , Fígado , Interpretação de Imagem Radiográfica Assistida por Computador , Software , Humanos , Reprodutibilidade dos Testes , Hepatectomia/métodos , Masculino , Feminino , Fígado/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Tamanho do Órgão , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Curva de Aprendizado , Adulto , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Variações Dependentes do Observador , Estudos Retrospectivos , Idoso de 80 Anos ou maisRESUMO
We aimed to evaluate the practice and the associated outcomes of surgical treatment for young-onset colorectal cancer (YOCRC) patients presenting with synchronous liver metastases. The study cohort was divided into two groups according to surgery date: 131 patients in the early era (EE, 1998-2011) and 179 in the contemporary era (CE, 2012-2020). The CE had a higher rate of node-positive primary tumors, higher carcinoembryonic antigen level, and lower rate of RAS/BRAF mutations. The CE had higher rates of reverse or combined resection, multi-drug prehepatectomy chemotherapy, and two-stage hepatectomy. The median survival was 8.4 years in the CE and 4.3 years in the EE (p = 0.011). On multivariate analysis, hepatectomy in the CE was independently associated with improved overall survival (HR 0.48, p = 0.001). With a combination of perioperative systemic therapy, careful selection of treatment approach, and coordinated resections, durable cure can be achieved in YOCRC patients.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Hepatectomia/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Postoperative hepatic insufficiency (PHI) is the most feared complication after hepatectomy. Volume of the future liver remnant (FLR) is one objectively measurable indicator to identify patients at risk of PHI. In this review, we summarized the development and rationale for the use of liver volumetry and liver-regenerative interventions and highlighted emerging tools that could yield new advancements in liver volumetry. METHODS: A review of MEDLINE/PubMed, Embase, and Cochrane Library databases was conducted to identify literature related to liver volumetry. The references of relevant articles were reviewed to identify additional publications. RESULTS: Liver volumetry based on radiologic imaging was developed in the 1980s to identify patients at risk of PHI and later used in the 1990s to evaluate grafts for living donor living transplantation. The field evolved in the 2000s by the introduction of standardized FLR based on the hepatic metabolic demands and in the 2010s by the introduction of the degree of hypertrophy and kinetic growth rate as measures of the FLR regenerative and functional capacity. Several liver-regenerative interventions, most notably portal vein embolization, are used to increase resectability and reduce the risk of PHI. In parallel with the increase in automation and machine assistance to physicians, many semi- and fully automated tools are being developed to facilitate liver volumetry. CONCLUSION: Liver volumetry is the most reliable tool to detect patients at risk of PHI. Advances in imaging analysis technologies, newly developed functional measures, and liver-regenerative interventions have been improving our ability to perform safe hepatectomy.
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Hepatectomia , Regeneração Hepática , Fígado , Humanos , Hepatectomia/métodos , Tamanho do Órgão , Fígado/diagnóstico por imagem , Fígado/cirurgia , Insuficiência Hepática/etiologia , Embolização Terapêutica/métodos , Complicações Pós-Operatórias/etiologia , Transplante de Fígado/métodos , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgiaAssuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Diagnóstico por ImagemRESUMO
CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of incidental ring-hyperenhancing liver micronodules (RHLMs) and investigated whether there is a correlation of RHLMs with histologic analysis or intrahepatic tumor progression at imaging follow-up after applying a biomechanical deformable image registration method. The analysis revealed 25 incidental RHLMs in 41.7% (10 of 24) of the CTHA images from the respective guided ablation sessions. Of those, four RHLMs were ablated. Among the remaining 21 RHLMs, 71.4% (15 of 21) were confirmed to be CLM with either histology (n = 3) or imaging follow-up (n = 12). The remaining 28.6% (six of 21) of RHLMs were not observed at follow-up imaging. This suggests that RHLMs at CTHA may be an early indicator of incidental small CLMs. Keywords: Colorectal Neoplasms, Liver, Angiography, CT, Incidental Findings, Ablation Supplemental material is available for this article. © RSNA, 2024.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/diagnóstico por imagem , Angiografia/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Distinguishing malignant from benign causes of obstruction at the liver hilum can pose a diagnostic dilemma. This study aimed to determine factors that predict benign causes of hilar obstruction and long-term outcomes after resection. METHODS: Consecutive patients who underwent surgery for hilar obstruction at a single institution between 1997 and 2022 were retrospectively analyzed. Median follow-up was 26 months (range 0-281 months). RESULTS: Among 182 patients who underwent surgery for hilar obstruction, 25 (14%) patients were found to have benign disease. Median CA19-9 level after normalization of serum bilirubin was 80 U/mL (range 1-5779) and 21 U/mL (range 1-681) among patients with malignant and benign strictures, respectively (p = 0.001). Cross-sectional imaging features associated with malignancy were lobar atrophy, soft tissue mass/infiltration, and vascular involvement (all p < 0.05). Factors not correlated with malignancy were jaundice upon presentation, peak serum bilirubin, sex, and race. Preoperative bile duct brushing or biopsy had sensitivity and specificity rates of 82% and 55%, respectively. Among patients who underwent resection with curative intent, grade 3-4 complications occurred in 55% and 29% of patients with malignant and benign strictures, respectively (p = 0.028). Postoperative long-term complications of chronic portal hypertension and recurrent cholangitis occurred in ≥ 10% of patients with both benign and malignant disease (p = non-significant). CONCLUSIONS: Strictures at the liver hilum continue to present diagnostic and management challenges. Postoperative complications and long-term sequelae of portal hypertension and recurrent cholangitis develop in a significant number of patients after resection of both benign and malignant strictures.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colangite , Hipertensão Portal , Neoplasias , Humanos , Estudos Retrospectivos , Constrição Patológica/cirurgia , Bilirrubina , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgiaRESUMO
BACKGROUND: Early recurrence following hepatectomy for colorectal liver metastases (CLM) is associated with worse survival; yet, impact of further local therapy is unclear. We sought to evaluate whether local therapy benefits patients with early recurrence following hepatectomy for CLM. METHODS: Clinicopathologic and survival outcomes of patients managed with hepatectomy for CLM (1/2001-12/2020) were queried from a prospectively maintained database. Timing of recurrence was stratified as early (recurrence-free survival [RFS] < 6 months), intermediate (RFS 6-12 months), and later (RFS > 12 months). Local therapy was defined as ablation, resection, or radiation. RESULTS: Of 671 patients, 541 (81%) recurred with 189 (28%) early, 180 (27%) intermediate, and 172 (26%) later recurrences. Local therapy for recurrence resulted in improved survival, regardless of recurrence timing (early 78 vs. 32 months, intermediate 72 vs. 39 months, later 132 vs. 65 months, all p < 0.001). Following recurrence, treatment with local therapy (hazard ratio [HR] = 0.24), liver and extrahepatic recurrence (HR = 1.81), RAS + TP53 co-mutation (HR = 1.52), and SMAD4 mutation (HR = 1.92) were independently associated with overall survival (all p ≤ 0.002). Among patients with recurrence treated by local therapy, patients older than 65 years (HR 1.79), liver and extrahepatic recurrence (HR 2.05), primary site or other recurrence (HR 1.90), RAS-TP53 co-mutation (HR 1.63), and SMAD4 mutation (HR 2.06) had shorter post-local therapy survival (all p ≤ 0.04). CONCLUSIONS: While most patients recur after hepatectomy for CLM, local therapy may result in long-term survival despite early recurrence. Somatic mutational profiling may help to guide the multidisciplinary consideration of local therapy after recurrence.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Prognóstico , Neoplasias Colorretais/patologia , Hepatectomia , Modelos de Riscos Proporcionais , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/patologia , Taxa de Sobrevida , Estudos RetrospectivosRESUMO
BACKGROUND: While risk-stratified post-hepatectomy pathways (RSPHPs) reduce length-of-stay, can they stratify hepatectomy patients by risk of early postoperative events. METHODS: 90-day outcomes from consecutive hepatectomies were analyzed (1/1/2017-12/31/2021). Pre/post-pathway analysis was performed for pathways: minimally invasive surgery ("MIS"); non-anatomic resection/left hepatectomy ("low-intermediate risk"); right/extended hepatectomy ("high-risk"); "Combination" operations. Time-to-event (TTE) analyses for readmission and interventional radiology procedures (IRPs) was performed. RESULTS: 1354 patients were included: MIS/n= â119 (9 â%); low-intermediate risk/n= â443 (33 â%); high-risk/n= â328 (24 â%); Combination/n= â464 (34 â%). There was no difference in readmission (pre: 13 â% vs. post:11.5 â%, p â= â0.398). There were fewer readmissions in post-pathway patients amongst MIS, low-intermediate risk, and Combination patients (all p â> â0.1). 114 (8.4 â%) patients required IRPs. Time-to-readmission and time-to-IR-procedure plots demonstrated lower plateaus and flatter slopes for MIS/low-intermediate-risk pathways post-pathway implementation (p â< â0.001). CONCLUSION: RSPHPs can reliably stratify patients by risks of readmission or need for an IR procedure by predicting the most frequent period for these events.
Assuntos
Hepatectomia , Alta do Paciente , Readmissão do Paciente , Complicações Pós-Operatórias , Humanos , Hepatectomia/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Medição de Risco , Estudos Retrospectivos , Tempo de Internação/estatística & dados numéricos , Neoplasias Hepáticas/cirurgiaRESUMO
BACKGROUND: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems. METHODS: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created. RESULTS: We identified 383 patients with HCC with imaging and survival outcomes, nâ =â 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems. CONCLUSIONS: Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
Cancer stem cells (CSC) play a critical role in metastasis, relapse, and therapy resistance in colorectal cancer. While characterization of the normal lineage of cell development in the intestine has led to the identification of many genes involved in the induction and maintenance of pluripotency, recent studies suggest significant heterogeneity in CSC populations. Moreover, while many canonical colorectal cancer CSC marker genes have been identified, the ability to use these classical markers to annotate stemness at the single-cell level is limited. In this study, we performed single-cell RNA sequencing on a cohort of 6 primary colon, 9 liver metastatic tumors, and 11 normal (nontumor) controls to identify colorectal CSCs at the single-cell level. Finding poor alignment of the 11 genes most used to identify colorectal CSC, we instead extracted a single-cell stemness signature (SCS_sig) that robustly identified "gold-standard" colorectal CSCs that expressed all marker genes. Using this SCS_sig to quantify stemness, we found that while normal epithelial cells show a bimodal distribution, indicating distinct stem and differentiated states, in tumor epithelial cells stemness is a continuum, suggesting greater plasticity in these cells. The SCS_sig score was quite variable between different tumors, reflective of the known transcriptomic heterogeneity of CRC. Notably, patients with higher SCS_sig scores had significantly shorter disease-free survival time after curative intent surgical resection, suggesting stemness is associated with relapse. IMPLICATIONS: This study reveals significant heterogeneity of expression of genes commonly used to identify colorectal CSCs, and identifies a novel stemness signature to identify these cells from scRNA-seq data.
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Neoplasias Colorretais , Recidiva Local de Neoplasia , Humanos , Recidiva Local de Neoplasia/patologia , Perfilação da Expressão Gênica , Neoplasias Colorretais/patologia , Recidiva , Análise de Sequência de RNA , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular TumoralRESUMO
BACKGROUND: The prognostic relevance of laterality, microsatellite instability (MSI), and KRAS status in colon cancer has been established. However, their effect on conditional overall survival (COS) remains unknown. METHODS: COS is the probability of surviving additional years after a time from diagnosis. The National Cancer Database (2010-2017) was queried for adults with non-metastatic colon cancer and known mutation status undergoing curative resection. COS was investigated at 2 years. RESULTS: Of 4838 patients, 3716 survived at least 2 years: 15% had stage I, 38% stage II, and 46% stage III disease. Fifty-nine percent had a right-sided tumor, 16% were MSI-high, and 37% were mutated KRAS (mKRAS). The proportion of patients alive at 2 years was higher for stage I compared with stage II and III (65 vs. 61 vs. 54%). The 5-year overall survival for stage I-III was 80, 76, and 67% for the initial cohort, and 90, 88, and 86% for those alive at 2 years. After adjustment, higher pathologic T and N stage, tumor deposits, and no chemotherapy were associated with worse COS (p < 0.01). While laterality and MSI status were not associated with COS, mKRAS was independently associated with decreased COS (HR 1.35, 95% CI 1.12-1.62). CONCLUSION: Patients with mKRAS had worse COS, suggesting that these mutations confer an aggressive biologic behavior, with patients remaining at higher risk of death 2 years after diagnosis. Routine evaluation of KRAS status should be considered in patients with non-metastatic disease for prognostication and to identify those who might benefit from modified surveillance protocols.