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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.
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Pancreaticoduodenectomía , Hemorragia Posoperatoria , Humanos , Pancreaticoduodenectomía/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/epidemiología , Duodeno/irrigación sanguínea , IncidenciaRESUMEN
BACKGROUND: Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC. METHODS: We conducted a single-center, retrospective observational study using institutional databases. Clinical data and outcomes for patients with stage IV PDAC and at least one documented episode of AC, were assessed. Overall survival (OS) was estimated using the Kaplan-Meier method, and Cox regression model was employed to identify predictors of AC recurrence and mortality. RESULTS: One hundred and twenty-four patients with stage IV PDAC and AC identified between January 01, 2014 and October 31, 2020 were included. Median OS after first episode of AC was 4.1 months (95 % CI, 4.0-5.5), and 30-day, 6, and 12-month survival was 86.2 % (95 % CI, 80.3-92.5), 37 % (95 % CI, 29.3-46.6 %) and 18.9 % (95 % CI, 13.1-27.3 %), respectively. Primary tumor in pancreatic body/tail (HR 2.29, 95 % CI: 1.26 to 4.18, p = 0.011), concomitant metastases to liver and other sites (HR 1.96, 95 % CI: 1.16 to 3.31, p = 0.003) and grade 3 AC (HR 2.26, 95 % CI: 1.45 to 3.52, p < 0.001), predicted worse outcomes. Intensive care unit admission, sepsis, systemic therapy, treatment regimen, and time to intervention did not predict survival or risk of recurrence of AC. CONCLUSIONS: AC confers significant morbidity and mortality in advanced PDAC. Worse outcomes are associated with higher grade AC, primary tumor location in pancreatic body/tail, and metastases to liver and other sites.
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Colangitis , Neoplasias Pancreáticas , Humanos , Colangitis/complicaciones , Colangitis/mortalidad , Masculino , Femenino , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Estadificación de Neoplasias , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/patología , Anciano de 80 o más Años , Adenocarcinoma/mortalidad , Adenocarcinoma/complicaciones , Adenocarcinoma/patología , Enfermedad Aguda , Factores de RiesgoRESUMEN
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
The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112-444, range), and 18/21 (85.7%) patients received 112-140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4-61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3-58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8-27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.
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Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Radioisótopos de Itrio , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/terapia , Masculino , Femenino , Anciano , Embolización Terapéutica/métodos , Radioisótopos de Itrio/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Guidewire-facilitated access to peripheral vessels is commonplace in vascular access, but guidewire insertion into small vessels, such as the radial and distal radial arteries, can still be challenging. Failure to gain access on the first attempt may contribute to increased risks of procedural complications, such as vessel dissection, spasm, and occlusion. This research assessed the safety and efficacy of radial and distal radial artery access using a novel, FDA-cleared, small-core-diameter guidewire with an articulating tip, under ultrasound guidance. METHODS: This was a prospective, single-arm, single-center trial. Patients in need of vascular access were screened for participation and enrolled in the study. Guidewire insertion was attempted by four physicians (three interventional radiologists and an interventional nephrologist) at 162 arterial sites-65 radial and 97 distal radial, having a mean diameter of 2.0 mm. RESULTS: First-attempt successful placement of the guidewire in the artery occurred at 87.6% of access sites (142/162) and differences in the success rate between the radial and distal radial arteries or between vessels with diameter smaller or larger than 2 mm were not observed (62/68 and 67/77, respectively; p = 0.6). Four of the five reported adverse events were unrelated to the study device or procedure. Two of the three distal radial artery spasms occurred before the guidewire was used. The other two events were a radial artery spasm, and a distal radial artery site hematoma. All adverse events resolved spontaneously. CONCLUSIONS: First-attempt placement of a novel articulating tip guidewire in the radial and distal radial arteries occurred at a high rate in our study and was not associated with safety concerns.
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In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.
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Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Neoplasias de la Vesícula Biliar , Neoplasias Hepáticas , Humanos , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/terapia , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/terapia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Conductos Biliares IntrahepáticosRESUMEN
Background: Despite considerable advances in preoperative imaging, up to one-third of patients operatively explored for hepatic colorectal metastases are unexpectedly found to harbor unresectable intrahepatic or extrahepatic disease. Methods: The current study is a prospective, blinded study comparing utility of [18F]2-fluoro-2-deoxyglucose positron emission tomography (18F-FDG-PET) to computed tomography (CT) and CT arterial portography (CTAP) as preoperative staging. Results: The 125 planned subjects were enrolled. Findings seen on FDG-PET alone changed therapy for 23 of 125 patients (18%). FDG-PET confirmed other radiologic findings in 16 cases (13%), for an overall influence on therapy in 39 cases (31%). FDG-PET was the most sensitive diagnostic imaging test for extrahepatic cancer; it was 80-90% sensitive for extrahepatic cancer and 70-90% specific. For the 28 cases of unresectable disease due to extrahepatic disease, FDG-PET findings solely changed therapies in 16 cases (57%) and influenced therapy in seven other cases (25%). Of the 21 unresectable cases due to extent of intrahepatic disease, FDG-PET did not solely change therapy in any. Overall, FDG-PET had the lowest sensitivity for hepatic sites compared with CT or CTAP. In particular, small (<1 cm) liver tumors were particularly poorly detected by FDG-PET. The area under the receiver operating characteristic (ROC) curve for small tumors was 0.58 and for patients on chemotherapy it was 0.66, a modest improvement over no imaging. Conclusions: FDG-PET is an important test for preoperative staging of patients with hepatic colorectal metastases, affecting treatment decisions in nearly one-third of patients. The high yield is due mainly to detection of extrahepatic disease. It is therefore recommended in patients with extrahepatic lesions suspected to be disseminated cancer or those with high risk for extrahepatic disease. It is not a good test for identification of small tumors in the liver.
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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide accounting for over 800,000 new cases in 2018, with the highest incidence in Asia and Africa where hepatitis B is the most common risk factor. In Europe, Japan, and the United States, hepatitis C chronic alcohol abuse and non-alcoholic fatty liver disease are more common risk factors. Five-year survival is low, less than 20% worldwide. HCC is a particularly challenging disease to treat because therapeutic options and prognosis must also consider hepatitis or cirrhosis independent of the malignancy. Locoregional therapies (LRT) including ablation, arterially directed therapy and external beam radiation are the preferred treatments for patients with good performance status, unresectable disease limited to the liver and preserved liver function. In practice, patients with portal vein tumor thrombus and limited extrahepatic disease may also be considered candidates for LRT. There are several guidelines developed by expert panels provide recommendations on treating this challenging disease including the Barcelona Clinic Liver Cancer, European Association for the Study of the Liver, European Society for Medical Oncology, American Association for the Study of the Liver Diseases, and the National Comprehensive Cancer Network. The purpose of this paper is to review the guidelines as they are applied clinically in regions with high incidence of HCC.
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Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Europa (Continente)/epidemiología , Hepatitis B/complicaciones , Humanos , Neoplasias Hepáticas/patología , América del Norte , Estados UnidosRESUMEN
BACKGROUND: Thermal ablation is a definitive local treatment for selected colorectal liver metastases (CLM) that can be ablated with adequate margins. A critical limitation has been local tumor progression (LTP). METHODS: This prospective, single-group, phase 2 study enrolled patients with CLM < 5 cm in maximum diameter, at a tertiary cancer center between November 2009 and February 2019. Biopsy of the ablation zone center and margin was performed immediately after ablation. Viable tumor in tissue biopsy and ablation margins < 5 mm were assessed as predictors of 12-month LTP. RESULTS: We enrolled 107 patients with 182 CLMs. Mean tumor size was 2.0 (range, 0.6-4.6) cm. Microwave ablation was used in 51% and radiofrequency ablation in 49% of tumors. The 12- and 24-month cumulative incidence of LTP was 22% (95% confidence interval [CI]: 17, 29) and 29% (95% CI: 23, 36), respectively. LTP at 12 months was 7% (95% CI: 3, 14) for the biopsy tumor-negative ablation zone with margins ≥ 5 mm vs. 63% (95% CI: 35, 85) for the biopsy-positive ablation zone with margins < 5 mm (p < 0.001). CONCLUSIONS: Biopsy-proven complete tumor ablation with margins of at least 5 mm achieves optimal local tumor control for CLM, regardless of the ablation modality used.
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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
Management of malignant bile duct obstruction is both a clinically important and technically challenging aspect of caring for patients with advanced malignancy. Bile duct obstruction can be caused by extrinsic compression, intrinsic tumor/stone/debris, or by biliary ischemia, inflammation, and sclerosis. Common indications for biliary intervention include lowering the serum bilirubin level for chemotherapy, ameliorating pruritus, treating cholangitis or bile leak, and providing access for bile duct biopsy or other adjuvant therapies. In some institutions, biliary drainage may also be considered prior to hepatic or pancreatic resection. Prior to undertaking biliary intervention, it is essential to have high-quality cross-sectional imaging to determine the level of obstruction, the presence of filling defects or atrophy, and status of the portal vein. High bile duct obstruction, which we consider to be obstruction above, at, or just below the confluence (Bismuth classifications IV, III, II, and some I), is optimally managed percutaneously rather than endoscopically because interventional radiologists can target specific ducts for drainage and can typically avoid introducing enteric contents into isolated undrained bile ducts. Options for biliary drainage include external or internal/external catheters and stents. In the setting of high obstruction, placement of a catheter or stent above the ampulla, preserving the function of the sphincter of Oddi, may lower the risk of future cholangitis by preventing enteric contamination of the biliary tree. Placement of a primary suprapapillary stent without a catheter, when possible, is the procedure most likely to keep the biliary tree sterile.
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The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Sorafenib/uso terapéuticoRESUMEN
INTRODUCTION: The purpose of this study was to identify risk factors associated with local tumor progression-free survival (LTPFS) and complications after colorectal liver metastases (CLM) thermal ablation (TA). PATIENTS AND METHODS: This retrospective analysis included 286 patients with 415 CLM undergoing TA (radiofrequency and microwave ablation) in 378 procedures from January 2003 to July 2017. Prior hepatic artery infusion (HAI), bevacizumab, pre-existing biliary dilatation, ablation modality, minimal ablation margin (MM), prior hepatectomy, CLM number, and size were analyzed as factors influencing complications and LTPFS. Statistical analysis included the Kaplan-Meier method, Cox proportional hazards model, competing risk analysis, univariate/multivariate logistic/exact logistic regressions, and the Fisher exact test. Complications were reported according to modified Society of Interventional Radiology guidelines. RESULTS: The median follow-up was 31 months. There was no LTP for MM > 10 mm. Smaller tumor size, increased MM, and prior hepatectomy correlated with longer LTPFS. The major complications occurred following 28 (7%) of 378 procedures. There were no biliary complications in HAI-naive patients, versus 11% in HAI patients (P < .001), of which 7% were major. Biliary complications predictors in HAI patients included biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, ablation with 6 to 10 mm and > 10 mm MM resulted in major biliary complication rates of 4% and 21% (P = .0011), with corresponding LTP rates of 24% and 0% (P = .0033). In HAI-naive patients, the LTP rates for 6 to 10 mm and > 10 mm MM were 27% and 0%, respectively. CONCLUSIONS: No LTP was seen for MM > 10 mm. Biliary complications occurred only in HAI patients, especially in those with biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, MM of 6 to 10 mm resulted in 76% local tumor control and 4% major biliary complications incidence.
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Ablación por Catéter/métodos , Neoplasias Colorrectales/terapia , Hipertermia Inducida/métodos , Neoplasias Hepáticas/terapia , Anciano , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Alpelisib is a selective inhibitor of PI3Kα, shown to improve outcomes for PIK3CA mutant, hormone receptor positive (HR+) metastatic breast cancers (MBC) when combined with antiestrogen therapy. To uncover mechanisms of resistance, we conducted a detailed, longitudinal analysis of tumor and plasma circulating tumor DNA among such patients from a phase I/II trial combining alpelisib with an aromatase inhibitor (AI) (NCT01870505). The trial's primary objective was to establish safety with maculopapular rash emerging as the most common grade 3 adverse event (33%). Among 44 evaluable patients, the observed clinical benefit rate was 52%. Correlating genetic alterations with outcome, we identified loss-of-function PTEN mutations in 25% of patients with resistance. ESR1 activating mutations also expanded in number and allele fraction during treatment and were associated with resistance. These data indicate that genomic alterations that mediate resistance to alpelisib or antiestrogen may promote disease progression and highlight PTEN loss as a recurrent mechanism of resistance to PI3Kα inhibition.
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Inhibidores de la Aromatasa , Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inhibidores de la Aromatasa/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Moduladores de los Receptores de Estrógeno/uso terapéutico , Femenino , Humanos , Fosfohidrolasa PTEN/genética , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , TiazolesRESUMEN
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
OBJECTIVE. Industry relationships drive technologic innovation in interventional radiology and offer opportunities for professional growth. Women are underrepresented in interventional radiology despite the growing recognition of the importance of diversity. This study characterized gender disparities in financial relationships between industry and academic interventional radiologists. MATERIALS AND METHODS. In this retrospective cross-sectional study, U.S. academic interventional radiology physicians and their academic ranks were identified by searching websites of practices with accredited interventional radiology fellowship programs. Publicly available databases were queried to collect each physician's gender, years since medical school graduation, h-index, academic rank, and industry payments in 2018. Wilcoxon and chi-square tests compared payments between genders. A general linear model assessed the impact of academic rank, years since graduation, gender, and h-index on payments. RESULTS. Of 842 academic interventional radiology physicians, 108 (13%) were women. A total $14,206,599.41 was received by 686 doctors (81%); only $147,975.28 (1%) was received by women. A lower percentage of women (74%) than men (83%) received payments (p = 0.04); median total payments were lower for women ($535) than men ($792) (p = 0.01). Academic rank, h-index, years since graduation, and male gender were independent predictors of higher payments. Industry payments supporting technologic advancement were made exclusively to men. CONCLUSION. Female interventional radiology physicians received fewer and lower industry payments, earning 1% of total payments despite constituting 13% of physicians. Gender independently predicted industry payments, regardless of h-index, academic rank, or years since graduation. Gender disparity in interventional radiology physician-industry relationships warrants further investigation and correction.
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Docentes Médicos/estadística & datos numéricos , Industrias/economía , Industrias/estadística & datos numéricos , Médicos Mujeres/economía , Médicos Mujeres/estadística & datos numéricos , Radiología Intervencionista/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Retrospectivos , Distribución por SexoRESUMEN
BACKGROUND: This retrospective study reviews long-term outcome of hepatic artery embolization (HAE) using microspheres alone in patients presenting with Hepatocellular Carcinoma (HCC) and portal vein tumor (PVT). METHODS: From 2005 to 2015, 43 patients with HCC and PVT underwent HAE. Response to treatment, time-to-progression (TTP), local-tumor-progression (LTP), distant-hepatic-progression (DHP), PVT-progression (PVTP), and/or the development of extra-hepatic progression (EHP) were assessed on pre-HAE CT/MRI scans, within 4 weeks post-HAE and at quarterly intervals thereafter, along with liver function (Child-Pugh score, CP). RESULTS: Forty (40/43) patients progressed during a median follow-up of 10 months with a median TTP of 2.9 months. Eleven of the 40 patients (27.5%) developed EHP, with only 2 patients (5%) demonstrating solely LTP. Six patients (15%) developed PVTP only. At progression, 27 patients (27/40, 77%) maintained their initial CP status, including all 5 CP-B patients. Median survival was 12.5 (95% CI 8-23) months for the entire group; 17.3 (95% CI 10-33) months for the patients with segmental/lobar PVT, compared with 8.4 (95% CI 6-13) months for the patients with main PVT (p = 0.02). CONCLUSION: HAE can be used to treat patients with HCC and PVT with median survival of approximately a year and preserved liver function.
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Carcinoma Hepatocelular/terapia , Embolización Terapéutica , Neoplasias Hepáticas/terapia , Microesferas , Vena Porta , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
A 52-year-old African American man with small bowel adenocarcinoma metastatic to the brain and leptomeninges was found to have an acute pulmonary embolism while hospitalized for acute lower limb weakness, bowel, and urinary incontinence. He had an elevated troponin, echocardiographic findings concerning for right heart failure, and bilateral segmental and subsegmental pulmonary artery perfusion deficits with right pulmonary artery thrombus on CT angiography. Given the laboratory and radiographic findings with normotensive blood pressure, the patient was diagnosed with a submassive pulmonary embolism. After deliberation with interventional radiology and hematology, the patient underwent mechanical thrombectomy and was treated with therapeutic anticoagulation. Mechanical thrombectomy revealed substantial clot burden in the central pulmonary arteries and yielded a significant improvement in hypoxia and dyspnea. This case was an excellent exercise in therapeutic decision-making amidst a dynamic disease process that required integration of numerous clinical and diagnostic data points, including empiric anticoagulation with high clinical suspicion of acute pulmonary embolism, review of contraindications to anticoagulation and thrombolysis in metastatic malignancy, and the decision to pursue mechanical thrombectomy in the setting of contraindications to catheter-directed thrombolysis.
RESUMEN
PURPOSE: To assess the infection rate after eliminating postprocedural antibiotics in patients undergoing hepatic artery embolization (HAE) for primary and secondary hepatic malignancies. MATERIAL AND METHODS: In this historical cohort study, adults ≥18 years of age without prior biliary instrumentation or bypass who underwent HAE and received pre- and postprocedure antibiotic prophylaxis between September 1, 2014, and August 31, 2015, comprised group A, whereas similar patients receiving only preprocedure antibiotic prophylaxis between October 1, 2015, and September 30, 2016, comprised group B. Procedures conducted between September 1, 2015, and September 30, 2015, were excluded. The primary outcome was any infection occurring within 30 days of HAE. RESULTS: A total of 150 patients underwent 204 HAE procedures in group A, and 171 patients underwent 221 procedures in group B. Cefazolin given as a 1-g dose (or 2 grams if obese) was administered in 391 of 425 evaluable procedures (92%). Clindamycin plus gentamicin was prescribed in 34 patients (8%) who had severe penicillin allergy. There was significant improvement in adherence to the postprocedure antibiotic regimen, from 68% (138 of 204 procedures) to 98% (216 of 221 procedures) (P < .001) with elimination of postprocedure prophylaxis. There were no significant differences in 30-day infection rates (5 [3%] vs. 5 [2%]; P = .57), hospital readmissions (13 [6%] vs. 12 [5%]; P = .68), or all-cause mortality (3 [1%] vs. 3 [1%]; P = .62) between the 2 groups. CONCLUSIONS: Elimination of postprocedural antibiotics after HAE did not lead to an increase in infectious complications. This finding supports the 2018 Society of Interventional Radiology recommendation for preprocedural prophylaxis only for HAE in the setting of an intact sphincter of Oddi.
Asunto(s)
Antibacterianos/administración & dosificación , Profilaxis Antibiótica , Programas de Optimización del Uso de los Antimicrobianos , Infecciones Bacterianas/prevención & control , Embolización Terapéutica/efectos adversos , Arteria Hepática , Neoplasias Hepáticas/terapia , Procedimientos Innecesarios , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Profilaxis Antibiótica/efectos adversos , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/mortalidad , Esquema de Medicación , Embolización Terapéutica/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The aim of this study was to evaluate safety and survival following hepatic artery embolization (HAE) for metastatic solitary fibrous tumor (SFT) in the liver. All patients with SFT metastatic to liver treated with HAE were retrospectively analyzed. Tumor response was evaluated using mRECIST. Objective response, overall survival (OS), and progression-free survival (PFS) were evaluated using Kaplan-Meier and multivariate Cox proportional hazard ratio. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Twelve patients (6 males and 6 females, mean age: 42.5 ± 13 years; 24-65) were treated with 33 embolizations. Anatomical sites of origin for SFT were the head and neck (n = 6; 50%), pelvis (n = 2), pleura (n = 2), retroperitoneal (n = 1), and thigh (n = 1). The median follow-up from first HAE was 4.5 years (3-7.9). 84% of the patients showed objective response [42% complete response (CR) plus 42% partial response (PR)] to HAE by mRECIST (95% CI, 60-99%). Patients with CR to HAE had significantly higher OS compared to others (p < 0.02). The postembolization median OS was 4 years (95% CI, 2.3-5.2), and mean PFS, for intra- or extrahepatic progression of disease, was 6 months (95%, CI, 3.2-7.1). One patient developed pneumonia/sepsis and died 27 days postembolization, possibly not directly related to embolization. No grade III or IV adverse events were identified in the remaining patients. In conclusion, HAE for metastatic liver SFT is a relatively safe treatment option with high response rate and should be considered as a treatment option for metastatic liver SFT. In our cohort of patients with metastatic SFT to the liver, we observed a median OS of 4 years following HAE. Further studies are needed to confirm the efficacy of HAE.