RESUMEN
Histiocytic neoplasms are a heterogeneous group of clonal haematopoietic disorders that are marked by diverse mutations in the mitogen-activated protein kinase (MAPK) pathway1,2. For the 50% of patients with histiocytosis who have BRAFV600 mutations3-5, RAF inhibition is highly efficacious and has markedly altered the natural history of the disease6,7. However, no standard therapy exists for the remaining 50% of patients who lack BRAFV600 mutations. Although ERK dependence has been hypothesized to be a consistent feature across histiocytic neoplasms, this remains clinically unproven and many of the kinase mutations that are found in patients who lack BRAFV600 mutations have not previously been biologically characterized. Here we show ERK dependency in histiocytoses through a proof-of-concept clinical trial of cobimetinib, an oral inhibitor of MEK1 and MEK2, in patients with histiocytoses. Patients were enrolled regardless of their tumour genotype. In parallel, MAPK alterations that were identified in treated patients were characterized for their ability to activate ERK. In the 18 patients that we treated, the overall response rate was 89% (90% confidence interval of 73-100). Responses were durable, with no acquired resistance to date. At one year, 100% of responses were ongoing and 94% of patients remained progression-free. Cobimetinib treatment was efficacious regardless of genotype, and responses were observed in patients with ARAF, BRAF, RAF1, NRAS, KRAS, MEK1 (also known as MAP2K1) and MEK2 (also known as MAP2K2) mutations. Consistent with the observed responses, the characterization of the mutations that we identified in these patients confirmed that the MAPK-pathway mutations were activating. Collectively, these data demonstrate that histiocytic neoplasms are characterized by a notable dependence on MAPK signalling-and that they are consequently responsive to MEK inhibition. These results extend the benefits of molecularly targeted therapy to the entire spectrum of patients with histiocytosis.
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Azetidinas/uso terapéutico , Trastornos Histiocíticos Malignos/tratamiento farmacológico , Trastornos Histiocíticos Malignos/enzimología , Histiocitosis/tratamiento farmacológico , Histiocitosis/enzimología , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Piperidinas/uso terapéutico , Azetidinas/farmacología , Trastornos Histiocíticos Malignos/genética , Trastornos Histiocíticos Malignos/patología , Histiocitosis/genética , Histiocitosis/patología , Humanos , MAP Quinasa Quinasa 1/antagonistas & inhibidores , MAP Quinasa Quinasa 2/antagonistas & inhibidores , MAP Quinasa Quinasa 2/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mutación , Piperidinas/farmacología , Supervivencia sin Progresión , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-raf/genéticaRESUMEN
BACKGROUND: To assess the outcome of previously untreated patients with perihilar cholangiocarcinoma who present to a cancer referral center with or without pre-existing trans-papillary biliary drainage. METHODS: Consecutive patients with a diagnosis of perihilar cholangiocarcinoma presenting between January 1, 2013, and December 31, 2017, were identified from a prospective surgical database and by a query of the institutional database. Of 237 patients identified, 106 met inclusion criteria and were reviewed. Clinical information was obtained from the Electronic Medical Record and imaging studies were reviewed in the Picture Archiving and Communication System. RESULTS: 73 of 106 patients (69%) presenting with a new diagnosis of perihilar cholangiocarcinoma underwent trans-papillary biliary drainage (65 endoscopic and 8 percutaneous) prior to presentation at our institution. 8 of the 73 patients with trans-papillary biliary drainage (11%) presented with and 5 developed cholangitis; all 13 (18%) required subsequent intervention; none of the patients without trans-papillary biliary drainage presented with or required drainage for cholangitis (p = 0.008). Requiring drainage for cholangitis was more likely to delay treatment (p = 0.012) and portended a poorer median overall survival (13.6 months, 95%CI [4.08, not reached)] vs. 20.6 months, 95%CI [18.34, 37.51] p = 0.043). CONCLUSION: Trans-papillary biliary drainage for perihilar cholangiocarcinoma carries a risk of cholangitis and should be avoided when possible. Clinical and imaging findings of perihilar cholangiocarcinoma should prompt evaluation at a cancer referral center before any intervention. This would mitigate development of cholangitis necessitating additional drainage procedures, delaying treatment and potentially compromising survival.
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Neoplasias de los Conductos Biliares , Drenaje , Tumor de Klatskin , Humanos , Masculino , Tumor de Klatskin/cirugía , Tumor de Klatskin/mortalidad , Femenino , Neoplasias de los Conductos Biliares/cirugía , Anciano , Persona de Mediana Edad , Colangitis , Anciano de 80 o más Años , Resultado del Tratamiento , Adulto , Estudios RetrospectivosRESUMEN
BACKGROUND: To evaluate liver venous deprivation (LVD) outcomes in patients with colorectal liver metastasis (CRLM) heavily pretreated with systemic and hepatic arterial infusion pump (HAIP) chemotherapies that had an anticipated insufficient future liver remnant (FLR) hypertrophy after portal vein embolization (PVE). METHODS: PVE was performed with liquid embolics using a transsplenic or ipsilateral transhepatic approach. Simultaneously and via a trans-jugular approach, the right hepatic vein was embolized with vascular plugs. Liver volumetry was assessed on computed tomography before and 3-6 weeks after LVD. RESULTS: Twelve consecutive CRLM patients that underwent LVD before right hepatectomy or trisectionectomy were included, all previously treated with systemic chemotherapy for a mean of 11.9 months. Six patients had additional HAIP. After embolization, FLR ratio increased from 28.7% ± 5.9 to 42.2% ± 9.0 (P < 0.01). Mean kinetic growth rate (KGR) was 3.56%/week ± 2.3, with a degree of hypertrophy (DH) of 13.8% ± 7.1. In the HAIP subgroup, mean KGR and DH were respectively 3.58%/week ± 2.8 and 14.3% ± 8.7. No severe complications occurred. Ten patients reached surgery after 39 days ± 7.5. CONCLUSION: In heavily pretreated patients, LVD safely stimulated a rapid and effective FLR hypertrophy, with a resultant high rate of resection.
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Neoplasias del Colon , Embolización Terapéutica , Neoplasias Hepáticas , Neoplasias del Colon/patología , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Hepatectomía/efectos adversos , Venas Hepáticas , Humanos , Hígado/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Vena Porta/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver. MATERIAL AND METHODS: From October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35-78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1-9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient. RESULTS: The overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4-14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3-9.5). No grade 3-5 adverse events were detected in either group. CONCLUSIONS: HAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.
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Resinas Acrílicas/administración & dosificación , Embolización Terapéutica , Gelatina/administración & dosificación , Arteria Hepática , Neoplasias Hepáticas/terapia , Neoplasias Ováricas/terapia , Radiofármacos/administración & dosificación , Resinas Acrílicas/efectos adversos , Adulto , Anciano , Progresión de la Enfermedad , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/mortalidad , Femenino , Gelatina/efectos adversos , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Ciudad de Nueva York , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Tamaño de la Partícula , Supervivencia sin Progresión , Radiofármacos/efectos adversos , Estudios Retrospectivos , Factores de TiempoRESUMEN
Background Intermediate stage hepatocellular carcinomas (HCCs) are treated by inducing ischemic cell death with transarterial embolization (TAE) or transarterial chemoembolization (TACE). A subset of HCCs harbor nuclear factor E2-related factor 2 (NRF2), a major regulator of the oxidative stress response implicated in cell survival after ischemia. NRF2-mutated HCC response to TAE and/or TACE is unknown. Purpose To test whether ischemia resistance is present in individuals with NRF2-mutated HCC and if this resistance can be overcome by means of NRF2 inhibition in HCC cell lines. Materials and Methods This was a combined retrospective review of an institutional database (from January 2011 to December 2018) and prospective study (from January 2014 to December 2018) of participants with HCC who underwent TAE and a laboratory investigation of HCC cell lines. Imaging follow-up included liver CT or MRI at 1 month after the procedure followed by 3-month interval scans. Tumor radiologic response was assessed on the basis of follow-up imaging. The time to local progression after TAE for individuals with and individuals without NRF2 pathway alterations was estimated by using competing risk analysis (Gray test). The in vitro response to ischemia in four HCC cell lines with and without NRF2 overexpression was evaluated, and the combination of ischemia with NRF2 knockdown by means of short hairpin RNA or an NRF2 inhibitor was tested. Doubling time estimates, dose response curve regression, and comparison analyses were performed. Results Sixty-five individuals (median age, 69 years [range, 19-84 years]; 53 men) were evaluated. HCCs with NRF2 pathway mutation had a shorter time to local progression after TAE compared to those without mutation (6-month cumulative incidence of local progression, 56% [range, 19%-91%] vs 22% [range, 12%-34%], respectively; P < .001) and confirmed ischemia resistance in NRF2-overexpressing HCC cell lines. However, ischemia and NRF2 knock-down worked synergistically to decrease proliferation of NRF2-overexpressing HCC cell lines. Dose response curves of ML385, an NRF2 inhibitor, showed that ischemia induces addiction to NRF2 in cells with NRF2 alterations. Conclusion Hepatocellular carcinoma with nuclear factor E2-related factor 2 (NRF2) alterations showed resistance to ischemia, but ischemia simultaneously induced sensitivity to NRF2 inhibition. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Weiss and Nezami in this issue.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Factor 2 Relacionado con NF-E2/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Línea Celular Tumoral , Progresión de la Enfermedad , Embolización Terapéutica , Femenino , Humanos , Isquemia/genética , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: We investigated the efficacy and analyzed the complication risk factors of peritoneovenous shunt in treating refractory chylous ascites following retroperitoneal lymph node dissection in patients with urological malignancies. MATERIALS AND METHODS: From April 2001 to March 2019 all patients with refractory chylous ascites after retroperitoneal lymph node dissection treated with peritoneovenous shunt were reviewed. Demographic characteristics, technical success, efficacy, patency period and complications were studied. Univariate and multivariate logistic regression analysis was performed to identify predictors of complications. RESULTS: Twenty patients were included in this study. Testicular cancer was the most common malignancy (85%). The mean number of days from surgery to detection of chylous ascites was 21 days (SD 15, range 4 to 65). Ascites permanently resolved after peritoneovenous shunt in 18 patients (90%), leading to shunt removal in 17 patients (85%) between 46 and 481 days (mean 162, SD 141). The mean serum albumin level increased 24% after shunt placement (mean 3.0±0.6 gm/dl before, 3.9±0.8 gm/dl after, p <0.05). The most common complication was occlusion (30%). Relative risk of complications increased significantly when shunt placement was more than 70 days after surgery and in patients with more than 5 paracenteses before peritoneovenous shunt placement (AR 0.71% vs 0.25%, RR 2.9, p <0.048 and AR 0.6% vs 0.125%, RR 4.8, p <0.04, respectively). CONCLUSIONS: Peritoneovenous shunt permanently treated chylous ascites in 90% of patients after retroperitoneal lymph node dissection. Peritoneovenous shunt was removed in 85% of patients. Shunt placement is an effective and safe treatment option for refractory chylous ascites. These patients might benefit from earlier intervention, after 4 to 6 weeks of conservative management as opposed to 2 to 3 months.
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Ascitis Quilosa/cirugía , Escisión del Ganglio Linfático , Derivación Peritoneovenosa , Complicaciones Posoperatorias/cirugía , Neoplasias Urológicas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Escisión del Ganglio Linfático/métodos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Pronóstico , Espacio Retroperitoneal , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Neoplasias Urológicas/patología , Adulto JovenRESUMEN
Purpose To compare the effect of autologous blood patch injection (ABPI) with that of a hydrogel plug on the rate of pneumothorax at CT-guided percutaneous lung biopsy. Materials and Methods In this prospective randomized controlled trial ( https://ClinicalTrials.gov , NCT02224924), a noninferiority design was used for ABPI, with a 10% noninferiority margin when compared with the hydrogel plug, with the primary outcome of pneumothorax rate within 2 hours of biopsy. A type I error rate of 0.05 and 90% power were specified with a target study population of 552 participants (276 in each arm). From October 2014 to February 2017, all potential study participants referred for CT-guided lung biopsy (n = 2052) were assessed for enrollment. Results The data safety monitoring board recommended the trial be closed to accrual after an interim analysis met prespecified criteria for early stopping based on noninferiority. The final study group consisted of 453 participants who were randomly assigned to the ABPI (n = 226) or hydrogel plug (n = 227) arms. Of these, 407 underwent lung biopsy. Pneumothorax rates within 2 hours of biopsy were 21% (42 of 199) and 29% (60 of 208); chest tube rates were 9% (18 of 199) and 13% (27 of 208); and delayed pneumothorax rates within 2 weeks after biopsy were 1.4% (three of 199) and 1.5% (three of 208) in the ABPI and hydrogel plug arms, respectively. Conclusion Autologous blood patch injection is noninferior to a hydrogel plug regarding the rate of pneumothorax after CT-guided percutaneous lung biopsy. © RSNA, 2018 Online supplemental material is available for this article.
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Terapia Biológica , Hidrogeles , Biopsia Guiada por Imagen , Pulmón , Neumotórax , Adulto , Anciano , Anciano de 80 o más Años , Terapia Biológica/efectos adversos , Terapia Biológica/métodos , Terapia Biológica/estadística & datos numéricos , Femenino , Humanos , Hidrogeles/administración & dosificación , Hidrogeles/uso terapéutico , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Biopsia Guiada por Imagen/estadística & datos numéricos , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/cirugía , Masculino , Persona de Mediana Edad , Neumotórax/epidemiología , Neumotórax/etiología , Neumotórax/prevención & control , Neumotórax/terapia , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Trasplante Autólogo , Adulto JovenRESUMEN
OBJECTIVE: Percutaneous tunneled drainage catheter (PTDC) placement is a palliative alternative to serial paracenteses in patients with end-stage cancer and refractory ascites. The impact of PTDC on quality of life (QoL) and long-term outcomes has not been prospectively described. The objective was to evaluate changes in QoL after PTDC. METHOD: Eligible adult patients with end-stage cancer undergoing PTDC placement for refractory ascites completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and McGill Quality of Life instruments before PTDC placement and at 2 to 7 days and 2 to 4 weeks after PTDC. Catheter function, complications, and laboratory values were assessed. Analysis of QoL data was evaluated with a stratified Wilcoxon signed-rank test. RESULT: Fifty patients enrolled. Survey completion ranged from 65% to 100% (median 88%) across timepoints. All patients had a Tenckhoff catheter, with 98% technical success. Median survival after PTDC was 38 days (95% confidence interval = 32, 57 days). European Organization for Research and Treatment of Cancer scores showed improvement in global QoL (p = 0.03) at 1 week postprocedure (PP). Significant symptom improvement was reported for fatigue, nausea/vomiting, pain, dyspnea, insomnia, and appetite at 1 week PP and was sustained at 3 weeks PP for dyspnea (p < 0.01), insomnia (p < 0.01), and appetite loss (p = 0.03). McGill Quality of Life demonstrated overall QoL improvement at 1 (p = 0.03) and 3 weeks (p = 0.04) PP. Decline in sodium and albumin values pre- and post-PTDC slowed significantly (albumin slope -0.43 to -0.26, p = 0.055; sodium slope -2.50 to 1.31, p = 0.04). Creatinine values increased at an accelerated pace post-PTDC (0.040 to 0.21, p < 0.01). Thirty-eight catheter-related complications occurred in 24 of 45 patients (53%). SIGNIFICANCE OF RESULTS: QoL and symptoms improved after PTDC placement for refractory ascites in patients with end-stage malignancy. Decline in sodium and albumin values slowed postplacement. This study supports the use of a PTDC for palliation of refractory ascites in cancer patients.
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Ascitis/complicaciones , Neoplasias/terapia , Cuidados Paliativos/normas , Paracentesis/normas , Adulto , Anciano , Ascitis/psicología , Femenino , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Paracentesis/métodos , Estudios Prospectivos , Calidad de Vida/psicología , Encuestas y CuestionariosRESUMEN
PURPOSE: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes. MATERIALS AND METHODS: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq ± 1.8) between January 2011 and September 2017 after receiving ≥ 3 lines of chemotherapy. Twenty-four underwent genetic profiling with MSK-IMPACT or Sequenom; 26 had positron-emission tomography (PET)/CT imaging before and after treatment. Survival after the first radioembolization and 2-4-month PET/CT imaging response were assessed. Laboratory and imaging features were assessed to determine variables predictive of outcomes. Unpaired Student t tests and Fisher exact tests were used to compare responders and nonresponders categorized by changes in fluorodeoxyglucose avidity. Kaplan-Meier survival analysis was used to determine the impact of predictors on survival after radioembolization. RESULTS: Median survival after radioembolization was 11 months (range, 1-49 mo). Most patients (18 of 26; 69%) had complete or partial response based on changes in fluorodeoxyglucose avidity. Imaging response was associated with longer survival (P = .005). Whereas 100% of patients with PI3K pathway mutations showed an imaging response, only 45% of wild-type patients showed a response (P = .01). Median survival did not differ between PI3K pathway wild-type (10.9 mo) and mutant (undefined) patients (P = .50). CONCLUSIONS: These preliminary data suggest that genomic profiling may predict which patients with metastatic breast cancer benefit most from radioembolization. PI3K pathway mutations are associated with improved imaging response, which is associated with longer survival.
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Neoplasias de la Mama/diagnóstico por imagen , Embolización Terapéutica/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Mutación , Fosfatidilinositol 3-Quinasas/genética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos/administración & dosificación , Adulto , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Toma de Decisiones Clínicas , Análisis Mutacional de ADN , Embolización Terapéutica/efectos adversos , Femenino , Perfilación de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Ciudad de Nueva York , Selección de Paciente , Proyectos Piloto , Medicina de Precisión , Valor Predictivo de las Pruebas , Datos Preliminares , Radiofármacos/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Transducción de Señal/genética , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To identify common gene mutations in patients with neuroendocrine liver metastases (NLM) undergoing transarterial embolization (TAE) and establish relationship between these mutations and response to TAE. MATERIALS AND METHODS: Patients (n = 51; mean age 61 y; 29 men, 22 women) with NLMs who underwent TAE and had available mutation analysis were identified. Mutation status and clinical variables were recorded and evaluated in relation to hepatic progression-free survival (HPFS) (Cox proportional hazards) and time to hepatic progression (TTHP) (competing risk proportional hazards). Subgroup analysis of patients with pancreatic NLM was performed using Fisher exact test to identify correlation between mutation and event (hepatic progression or death) by 6 months. Changes in mutation status over time and across specimens in a subset of patients were recorded. RESULTS: Technical success of TAE was 100%. Common mutations identified were MEN1 (16/51; 31%) and DAXX (13/51; 25%). Median overall survival was 48.7 months. DAXX mutation status (hazard ratio = 6.21; 95% confidence interval [CI], 2.67-14.48; P < .001) and tumor grade (hazard ratio = 3.05; 95% CI, 1.80-5.17; P < .001) were associated with shorter HPFS and TTHP on univariate and multivariate analysis. Median HPFS was 3.6 months (95% CI, 1.7-5.3) for patients with DAXX mutation compared with 8.9 months (95% CI, 6.6-11.4) for patients with DAXX wild-type status. In patients with pancreatic NLMs, DAXX mutation status was associated with hepatic progression or death by 6 months (P = .024). DAXX mutation status was concordant between primary and metastatic sites. CONCLUSIONS: DAXX mutation is common in patients with pancreatic NLMs. DAXX mutation status is associated with shorter HPFS and TTHP after TAE.
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Proteínas Adaptadoras Transductoras de Señales/genética , Biomarcadores de Tumor/genética , Embolización Terapéutica/métodos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Mutación , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/terapia , Proteínas Nucleares/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Co-Represoras , Análisis Mutacional de ADN , Progresión de la Enfermedad , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/mortalidad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Chaperonas Moleculares , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/secundario , Fenotipo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of this study is to evaluate the accuracy of percutaneous fine needle biopsy (FNB) and brush biopsy (BB) at a cancer center. MATERIAL AND METHODS: Retrospective analysis of all bile duct biopsies performed in Interventional Radiology between January 2000 and January 2015 was performed. FNB was performed under real-time cholangiographic guidance using a notched needle directed at the bile duct stricture. BB was performed by advancing a brush across the stricture and moving it back and forth to scrape the stricture. Biopsy results were categorized as true positive (TP), true negative (TN), false positive (FP) and false negative (FN) based on pathology reports and confirmed by surgical specimens or clinical follow-up of at least six months. Fisher's exact test was used to compare the rate of TP in FNB and BB. RESULTS: One-hundred and nineteen patients underwent FNB or BB. Fifteen were censored because of lack of follow-up. The remaining 104 patients underwent a total of 117 bile duct biopsies during the study period: 34 FNB and 83 BB. There were no complications in either group. In the FNB group 22/34 (64%) biopsies were TP, 4/34(12%) were TN and there were 8(24%) FN biopsies. In the BB group, 20/83 (24%) were TP, 38/83 (46%) TN and 25/83 (30%) FN biopsies. There were no FP biopsies in either group. The sensitivity of detecting malignancy by FNB was significantly higher than that by BB (73% vs 44%, p < .0005). There were no complications associated with FNB or BB. CONCLUSIONS: FNB of bile duct strictures is safe and has a higher sensitivity for detecting malignancy than BB.
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Enfermedades de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/diagnóstico , Biopsia con Aguja Fina/métodos , Biopsia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/patología , Biopsia/efectos adversos , Biopsia con Aguja Fina/efectos adversos , Constricción Patológica/diagnóstico , Constricción Patológica/patología , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
PURPOSE: To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. MATERIALS AND METHODS: This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material-enhanced CT was used to assess technique effectiveness 4-8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2-4 months. Overall survival (OS) and local tumor progression-free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. RESULTS: Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. CONCLUSION: Tumor size of less than 3 cm and ablation margins greater than 5 mm are essential for satisfactory local tumor control. Tumor size of more than 3 cm and the presence of more than one site of EHD are associated with shorter OS.
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Ablación por Catéter/métodos , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética Intervencional/métodos , Radiografía Intervencional/métodos , Anciano , Medios de Contraste , Femenino , Hepatectomía/métodos , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Purpose To establish the prognostic value of biopsy of the central and marginal ablation zones for time to local tumor progression (LTP) after radiofrequency (RF) ablation of colorectal cancer liver metastasis (CLM). Materials and Methods A total of 47 patients with 67 CLMs were enrolled in this prospective institutional review board-approved and HIPAA-compliant study between November 2009 and August 2012. Mean tumor size was 2.1 cm (range, 0.6-4.3 cm). Biopsy of the center and margin of the ablation zone was performed immediately after RF ablation (mean number of biopsy samples per ablation zone, 1.9) and was evaluated for the presence of viable tumor cells. Samples containing tumor cells at morphologic evaluation were further interrogated with immunohistochemistry and were classified as either positive, viable tumor (V) or negative, necrotic (N). Minimal ablation margin size was evaluated in the first postablation CT study performed 4-8 weeks after ablation. Variables were evaluated as predictors of time to LTP with the competing-risks model (uni- and multivariate analyses). Results Technical effectiveness was evident in 66 of 67 (98%) ablated lesions on the first contrast material-enhanced CT images at 4-8-week follow-up. The cumulative incidence of LTP at 12-month follow-up was 22% (95% confidence interval [CI]: 12, 32). Samples from 16 (24%) of 67 ablation zones were classified as viable tumor. At univariate analysis, tumor size, minimal margin size, and biopsy results were significant in predicting LTP. When these variables were subsequently entered in a multivariate model, margin size of less than 5 mm (P < .001; hazard ratio [HR], 6.7) and positive biopsy results (P = .008; HR, 3.4) were significant. LTP within 12 months after RF ablation was noted in 3% (95% CI: 0, 9) of necrotic CLMs with margins of at least 5 mm. Conclusion Biopsy proof of complete tumor ablation and minimal ablation margins of at least 5 mm are independent predictors of LTP and yield the best oncologic outcomes. (©) RSNA, 2016.
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Ablación por Catéter/métodos , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Medios de Contraste , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Ondas de Radio , Resultado del Tratamiento , Carga TumoralRESUMEN
PURPOSE: To evaluate the incidence and risk factors of pneumothoraces requiring prolonged maintenance of a chest tube following CT-guided percutaneous lung biopsy in a retrospective, single-centre case series. MATERIALS AND METHODS: All patients undergoing CT-guided percutaneous lung biopsies between June 2012 and May 2014 who required chest tube insertion for symptomatic or enlarging pneumothoraces were identified. Based on chest tube dwell time, patients were divided into two groups: short term (0-2 days) or prolonged (3 or more days). The following risk factors were stratified between groups: patient demographics, target lesion characteristics, and procedural/periprocedural technique and outcomes. RESULTS: A total of 2337 patients underwent lung biopsy; 543 developed pneumothorax (23.2 %), 187 required chest tube placement (8.0 %), and 55 required a chest tube for 3 days or more (2.9 % of all biopsies, 29.9 % of all chest tubes). The median chest tube dwell time for short-term and prolonged groups was 1.0 days and 4.7 days, respectively. The transfissural needle path predicted prolonged chest tube requirement (OR: 2.5; p = 0.023). Other factors were not significantly different between groups. CONCLUSION: Of patients undergoing CT-guided lung biopsy, 2.9 % required a chest tube for 3 or more days. Transfissural needle path during biopsy was a risk factor for prolonged chest tube requirement. KEY POINTS: ⢠CT-guided percutaneous lung biopsy (CPLB) is an important method for diagnosing lung lesions ⢠A total of 2.9 % of patients require a chest tube for ≥3 days following CPLB ⢠Transfissural needle path is a risk factor for prolonged chest tube time.
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Tubos Torácicos , Neumotórax/etiología , Neumotórax/terapia , Radiografía Intervencional/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja/efectos adversos , Femenino , Humanos , Biopsia Guiada por Imagen/efectos adversos , Incidencia , Pulmón/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Toracotomía , TiempoRESUMEN
PURPOSE: To evaluate the safety and efficacy of percutaneous peritoneovenous shunt (PPVS) placement in treating intractable chylous ascites (CA) in patients with cancer. MATERIALS AND METHODS: Data from 28 patients with refractory CA treated with PPVS from April 2001 to June 2015 were reviewed. Demographic characteristics, technical success, efficacy, laboratory values, and complications were recorded. Univariate and multivariate logistic regression analysis was performed. RESULTS: Technical success was 100%, and ascites resolved or symptoms were relieved in 92.3% (26 of 28) of patients. In 13 (46%) patients with urologic malignancies, whose ascites had resulted from retroperitoneal lymph node dissection, the ascites resolved, resulting in shunt removal within 128 days ± 84. The shunt provided palliation of symptoms in 13 of the remaining 15 patients (87%) for a mean duration of 198 days ± 214. Serum albumin levels increased significantly (21.4%) after PPVS placement from a mean of 2.98 g/dL ± 0.64 before the procedure to 3.62 g/dL ± 0.83 (P < .001). The complication rate was 37%, including shunt malfunction/occlusion (22%), venous thrombosis (7%), and subclinical disseminated intravascular coagulopathy (DIC) (7%). Smaller venous limb size (11.5 F) and the presence of peritoneal tumor were associated with a higher rate of shunt malfunction (P < .05). No patient developed overt DIC. CONCLUSIONS: PPVS can safely and effectively treat CA in patients with cancer, resulting in significant improvement in serum albumin in addition to palliation of symptoms.
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Ascitis Quilosa/terapia , Neoplasias/complicaciones , Derivación Peritoneovenosa/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Ascitis Quilosa/sangre , Ascitis Quilosa/diagnóstico , Ascitis Quilosa/etiología , Coagulación Intravascular Diseminada/etiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cuidados Paliativos , Derivación Peritoneovenosa/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica/metabolismo , Albúmina Sérica Humana , Factores de Tiempo , Resultado del Tratamiento , Trombosis de la Vena/etiología , Adulto JovenRESUMEN
OBJECTIVE: Colorectal liver metastases (CLM) have a variable response to radioembolization. This may be due at least partly to differences in tumor arterial perfusion. The present study examines whether quantitative measurements of enhancement on preprocedure triphasic CT can be used to predict the response of CLM to radioembolization. MATERIALS AND METHODS: We retrospectively reviewed patients with CLM treated with radioembolization who underwent pretreatment PET/CT and triphasic CT examinations and posttreatment PET/CT examinations. A total of 31 consecutive patients with 60 target tumors were included in the present study. For each tumor, we calculated the hepatic artery coefficient (HAC), portal vein coefficient (PVC), and arterial enhancement fraction (AEF) based on enhancement measurements on pretreatment triphasic CT. HAC and PVC are estimates of the hepatic artery and portal vein blood supply. AEF, which is the arterial phase enhancement divided by the portal phase enhancement, provides an estimate of the hepatic artery blood supply as a fraction of the total blood supply. For each tumor, the metabolic response to radioembolization was based on findings from the initial follow-up PET/CT scan obtained at 4-8 weeks after treatment. RESULTS: A total of 55% of CLM had a complete or partial metabolic response. Arterial phase enhancement, the HAC, and the PVC did not predict which tumors responded to radioembolization. However, the AEF was statistically significantly greater in tumors with a complete or partial metabolic response than in tumors with no metabolic response (i.e., those with stable disease or disease progression) (p = 0.038). An AEF of less than 0.4 was associated with a 40% response rate, whereas an AEF greater than 0.75 was associated with a 78% response rate. CONCLUSION: Response to radioembolization can be predicted using the AEF calculated from the preprocedure triphasic CT.
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Neoplasias Colorrectales/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Aumento de la Imagen/métodos , Yohexol , Masculino , Microesferas , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Radioisótopos de Itrio/uso terapéuticoAsunto(s)
Procedimientos Quirúrgicos del Sistema Biliar/normas , Colecistostomía/normas , Mejoramiento de la Calidad/normas , Indicadores de Calidad de la Atención de Salud/normas , Radiología Intervencionista/normas , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Colecistostomía/efectos adversos , Consenso , Humanos , Seguridad del Paciente/normas , Factores de Riesgo , Resultado del TratamientoRESUMEN
PURPOSE: To identify factors affecting periprocedural morbidity and mortality and long-term survival following hepatic artery embolization (HAE) of hepatic neuroendocrine tumor (NET) metastases. MATERIALS AND METHODS: This single-center, institutional review board-approved retrospective review included 320 consecutive HAEs for NET metastases performed in 137 patients between September 1996 and September 2007. Forty-seven HAEs (15%) were performed urgently to manage refractory symptoms in inpatients (urgent group), and 273 HAEs (85%) were elective (elective group). Overall survival (OS) was estimated by Kaplan-Meier methodology. Complications were categorized per Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to determine independent predictors for OS, complications, and 30-day mortality. The independent factors were combined to develop clinical risk score groups. RESULTS: Urgent HAE (P = .007), greater than 50% liver replacement by tumor (P < .0001), and extrahepatic metastasis (P = .007) were independent predictors for shorter OS. Patients with all three risk factors had decreased OS versus those with none (median, 8.5 vs 86 mo; P < .001). Thirty-day mortality was significantly lower in the elective (1%) versus the urgent group (8.5%; P = .0009). There were eight complications (3%) in the elective group and five (10.6%) in the urgent group (P = .03). Male sex and urgent group were independent factors for higher 30-day mortality rate (P = .023 and P =.016, respectively) and complications (P = .012 and P =.001, respectively). CONCLUSIONS: Urgent HAE, replacement of more than 50% of liver by tumor, and extrahepatic metastasis are strong independent predictors of shorter OS. Male sex and urgent HAE carry higher 30-day mortality and periprocedural morbidity risks.
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Embolización Terapéutica , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Tumores Neuroendocrinos/secundario , Tumores Neuroendocrinos/terapia , Sobrevivientes , Adulto , Anciano , Anciano de 80 o más Años , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tumores Neuroendocrinos/mortalidad , Ciudad de Nueva York , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del TratamientoRESUMEN
Importance: Postpancreatectomy hemorrhage is an uncommon but highly morbid complication of pancreaticoduodenectomy. Clinical evidence often draws suspicion to the gastroduodenal artery stump, even without a clear source. Objective: To determine the frequency of gastroduodenal artery bleeding compared to other sites and the results of mitigation strategies. Design, Setting, and Participants: This cohort study involved a retrospective analysis of data for consecutive patients who had pancreaticoduodenectomy from 2011 to 2021 at Memorial Sloan Kettering Cancer Center (MSK) and Thomas Jefferson University Hospital (TJUH). Exposures: Demographic, perioperative, and disease-related variables. Main Outcomes and Measures: The incidence, location, treatment, and outcomes of primary (initial) and secondary (recurrent) hemorrhage requiring invasive intervention were analyzed. Imaging studies were re-reviewed by interventional radiologists to confirm sites. Results: Inclusion criteria were met by 3040 patients (n = 1761 MSK, n = 1279 TJUH). Patients from both institutions were similar in age (median [IQR] age at MSK, 67 [59-74] years, and at TJUH, 68 [60-75] years) and sex (at MSK, 814 female [46.5%] and 947 male [53.8%], and at TJUH, 623 [48.7%] and 623 male [51.3%]). Primary hemorrhage occurred in 90 patients (3.0%), of which the gastroduodenal artery was the source in 15 (16.7%), unidentified sites in 24 (26.7%), and non-gastroduodenal artery sites in 51 (56.7%). Secondary hemorrhage occurred in 23 patients; in 4 (17.4%), the gastroduodenal artery was the source. Of all hemorrhage events (n = 117), the gastroduodenal artery was the source in 19 (16.2%, 0.63% incidence in all pancreaticoduodenectomies). Gastroduodenal artery hemorrhage was more often associated with soft gland texture (14 [93.3%] vs 41 [62.1%]; P = .02) and later presentation (median [IQR], 21 [15-26] vs 10 days [5-18]; P = .002). Twenty-three patients underwent empirical gastroduodenal artery embolization or stent placement, 7 (30.4%) of whom subsequently experienced secondary hemorrhage. Twenty percent of all gastroduodenal artery embolizations/stents (8/40 patients), including 13% (3/13 patients) of empirical treatments, were associated with significant morbidity (7 hepatic infarction, 4 biliary stricture), with a 90-day mortality rate of 38.5% (n = 5) for patients with these complications vs 7.8% without (n = 6; P = .008). Ninety-day mortality was 12.2% (n = 11) for patients with hemorrhage (3 patients [20%] with primary gastroduodenal vs 8 [10.7%] for all others; P = .38) compared with 2% (n = 59) for patients without hemorrhage. Conclusions and Relevance: In this study, postpancreatectomy hemorrhage was uncommon and the spectrum was broad, with the gastroduodenal artery responsible for a minority of bleeding events. Empirical gastroduodenal artery embolization/stent without obvious sequelae of recent hemorrhage was associated with significant morbidity and rebleeding and should not be routine practice. Successful treatment of postpancreatectomy hemorrhage requires careful assessment of all potential sources, even after gastroduodenal artery mitigation.