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1.
BMC Gastroenterol ; 24(1): 181, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38783208

RESUMO

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.


Assuntos
Neoplasias dos Ductos Biliares , Drenagem , Tumor de Klatskin , Humanos , Masculino , Tumor de Klatskin/cirurgia , Tumor de Klatskin/mortalidade , Feminino , Neoplasias dos Ductos Biliares/cirurgia , Idoso , Pessoa de Meia-Idade , Colangite , Idoso de 80 Anos ou mais , Resultado do Tratamento , Adulto , Estudos Retrospectivos
2.
JAMA Surg ; 159(8): 891-899, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38776076

RESUMO

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.


Assuntos
Pancreaticoduodenectomia , Hemorragia Pós-Operatória , Humanos , Pancreaticoduodenectomia/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/epidemiologia , Duodeno/irrigação sanguínea , Incidência
3.
Curr Oncol ; 30(10): 9181-9191, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37887563

RESUMO

The safety and efficacy of hepatic artery embolization (HAE) in treating intrahepatic cholangiocarcinoma (IHC) was evaluated. Initial treatment response, local tumor progression-free survival (L-PFS), and overall survival (OS) were evaluated in 34 IHC patients treated with HAE. A univariate survival analysis and a multivariate Cox proportional hazard analysis to identify independent factors were carried out. Objective response (OR) at 1-month was 79.4%. Median OS and L-PFS from the time of HAE was 13 (CI = 95%, 7.4-18.5) and 4 months (CI = 95%, 2.09-5.9), respectively. Tumor burden < 25% and increased tumor vascularity on preprocedure imaging and surgical resection prior to embolization were associated with longer OS (p < 0.05). Multivariate logistic regression analysis demonstrated that tumor burden < 25% and hypervascular tumors were independent risk factors. Mean post-HAE hospital stay was 4 days. Grade 3 complication rate was 8.5%. In heavily treated patients with IHC, after exhausting all chemotherapy and other locoregional options, HAE as a rescue treatment option appeared to be safe with a mean OS of 13 months. Tumor burden < 25%, increased target tumor vascularity on pre-procedure imaging, and OR on 1 month follow-up images were associated with better OS. Further studies with a control group are required to confirm the effectiveness of HAE in IHC.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Resultado do Tratamento , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/terapia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/terapia
4.
Hepatobiliary Surg Nutr ; 11(4): 539-554, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36016741

RESUMO

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.

5.
Cancers (Basel) ; 14(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35158963

RESUMO

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.

6.
HPB (Oxford) ; 24(3): 404-412, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34452833

RESUMO

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.


Assuntos
Neoplasias do Colo , Embolização Terapêutica , Neoplasias Hepáticas , Neoplasias do Colo/patologia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Hepatectomia/efeitos adversos , Veias Hepáticas , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Veia Porta/cirurgia , Resultado do Tratamento
7.
Semin Intervent Radiol ; 38(3): 300-308, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34393340

RESUMO

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.

8.
Clin Colorectal Cancer ; 20(2): e82-e95, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33246789

RESUMO

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.


Assuntos
Ablação por Cateter/métodos , Neoplasias Colorretais/terapia , Hipertermia Induzida/métodos , Neoplasias Hepáticas/terapia , Idoso , Neoplasias Colorretais/patologia , Progressão da Doença , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
9.
Radiology ; 297(1): 225-234, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32780006

RESUMO

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.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Fator 2 Relacionado a NF-E2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Progressão da Doença , Embolização Terapêutica , Feminino , Humanos , Isquemia/genética , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Tomografia Computadorizada por Raios X
11.
J Urol ; 204(4): 818-823, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32364837

RESUMO

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.


Assuntos
Ascite Quilosa/cirurgia , Excisão de Linfonodo , Derivação Peritoneovenosa , Complicações Pós-Operatórias/cirurgia , Neoplasias Urológicas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Espaço Retroperitoneal , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias Urológicas/patologia , Adulto Jovem
12.
Sarcoma ; 2019: 3060658, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565028

RESUMO

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.

13.
Cardiovasc Intervent Radiol ; 42(8): 1135-1141, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31073823

RESUMO

PURPOSE: Estimate the incidence of nontarget embolization (NTE) as identified on immediate post-hepatic artery embolization CT. MATERIALS AND METHODS: Two hundred hepatic embolizations performed with particles alone (bland embolization) in 147 patients between August 16, 2013 and August 26, 2014 with immediate post-procedure CT were retrospectively reviewed. Arterial anatomy, vessels treated, imaging findings of NTE, patient demographics, length of hospital stay following embolization, and procedure-related complications were recorded. The data were analyzed using two-sided t-tests and chi-squared tests. RESULTS: Evidence of NTE was seen on post-procedure CT in 64 of 200 cases (64/200, 32%). Six organs were affected, with 69 discrete sites in 64 patients. The majority (49/69, 71.0%) involved the gallbladder. The mean length of hospital stay (LOS) for patients with and without NTE was 2.9 ± 1.5 nights (range 1-7) and 2.9 ± 2.3 nights (range 0-21), respectively (P = 0.81). NTE was more common following embolization of replaced or accessory hepatic vessels. There were three complications in the NTE group (3/64, 4.7%) following the embolization procedure, one of which was cholecystitis directly related to NTE. The other two were one incidence each of contrast-induced nephropathy and pneumonia. In the group without NTE, seven complications occurred (7/136, 5.1%, P = 0.889), including one death resulting from hepatic failure, two gastrointestinal bleeds, two hepatic abscesses, flash pulmonary edema, and pancreatitis. CONCLUSION: Unanticipated NTE is not uncommon after bland hepatic artery embolization, particularly after treating accessory or replaced vessels, but does not increase complications or LOS. LEVEL OF EVIDENCE: Level 2b, Retrospective Cohort.


Assuntos
Embolização Terapêutica/métodos , Artéria Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Órgãos em Risco/diagnóstico por imagem , Feminino , Artéria Hepática/patologia , Humanos , Incidência , Tempo de Internação/estatística & dados numéricos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Radiografia Intervencionista/métodos , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
14.
Nature ; 567(7749): 521-524, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30867592

RESUMO

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.


Assuntos
Azetidinas/uso terapêutico , Transtornos Histiocíticos Malignos/tratamento farmacológico , Transtornos Histiocíticos Malignos/enzimologia , Histiocitose/tratamento farmacológico , Histiocitose/enzimologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Piperidinas/uso terapêutico , Azetidinas/farmacologia , Transtornos Histiocíticos Malignos/genética , Transtornos Histiocíticos Malignos/patologia , Histiocitose/genética , Histiocitose/patologia , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 2/antagonistas & inibidores , MAP Quinase Quinase 2/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mutação , Piperidinas/farmacologia , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-raf/genética
15.
Radiology ; 290(2): 547-554, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30480487

RESUMO

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.


Assuntos
Terapia Biológica , Hidrogéis , Biópsia Guiada por Imagem , Pulmão , Pneumotórax , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Biológica/efeitos adversos , Terapia Biológica/métodos , Terapia Biológica/estatística & dados numéricos , Feminino , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/uso terapêutico , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/estatística & dados numéricos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Pneumotórax/prevenção & controle , Pneumotórax/terapia , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Transplante Autólogo , Adulto Jovem
16.
J Vasc Interv Radiol ; 29(11): 1519-1526, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30342802

RESUMO

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.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais/genética , Embolização Terapêutica/métodos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Mutação , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/terapia , Proteínas Nucleares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Correpressoras , Análise Mutacional de DNA , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/secundário , Fenótipo , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
J Vasc Interv Radiol ; 29(9): 1226-1235, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30078647

RESUMO

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.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Embolização Terapêutica/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Mutação , Fosfatidilinositol 3-Quinases/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/administração & dosagem , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Tomada de Decisão Clínica , Análise Mutacional de DNA , Embolização Terapêutica/efeitos adversos , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Cidade de Nova Iorque , Seleção de Pacientes , Projetos Piloto , Medicina de Precisão , Valor Preditivo dos Testes , Dados Preliminares , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Transdução de Sinais/genética , Fatores de Tempo , Resultado do Tratamento
19.
Minim Invasive Ther Allied Technol ; 27(5): 278-283, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29390936

RESUMO

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.


Assuntos
Doenças dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico , Biópsia por Agulha Fina/métodos , Biópsia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/patologia , Biópsia/efeitos adversos , Biópsia por Agulha Fina/efeitos adversos , Constrição Patológica/diagnóstico , Constrição Patológica/patologia , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
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