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BACKGROUND: Point-of-care-ultrasound (POCUS) improves diagnostic accuracy and expedites lifesaving procedures. Remote areas disproportionately underuse ultrasound (US) due to a dearth of US trained professionals, imaging tools, and lack of quality assurance. Handheld US probes have been approved for diagnostic imaging but there have been limited studies examining their tele-guidance features. This study investigates whether physician tele-guidance improved ultrasound image acquisition by untrained scanners. METHODS: To determine the effectiveness of tele-guidance for ultrasound image acquisition, 30 participants (15 in each study arm: experimental and control) with no ultrasound or medical experience gathered images of the heart, right kidney, and gallbladder of a standardized patient using a handheld ultrasound probe (Butterfly iQ +). All participants watched a standardized ultrasound tutorial video and were randomized into the control or experimental group. A physician assisted the experimental group using ultrasound probe's tele-guidance feature while the control group received no assistance. Time to image acquisition was recorded for both groups, and the images were graded by 3 blinded radiologists using the RACE tool to determine image and diagnostic quality. RESULTS: There was evidence that mean imaging time was greater in the control group for the heart, right kidney, and gallbladder (p < 0.0001, all; Cohen's DL: 2.0, 1.7, 3.0, respectively). Similarly, there was evidence that the predicted mean image quality for the heart, right kidney, and gallbladder was higher for the experimental group compared to the control group (3.46 versus 1.86, 4.49 versus 1.58, and 3.93 versus 1.5, respectively; p < 0.0001, all). There was also evidence that the diagnostic quality of images had a statistically higher predicted probability of meaningful interpretation for the experimental group for pericardial fluid, intraperitoneal fluid, and acute cholecystitis (p = 0.003, p < 0.0001, p < 0.0001, respectively). CONCLUSIONS: Tele-guidance improves time to image acquisition and clinical applicability of ultrasound images obtained by untrained scanners.
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Vesícula Biliar , Sistemas de Atención de Punto , Ultrasonografía , Humanos , Ultrasonografía/métodos , Estudios Prospectivos , Vesícula Biliar/diagnóstico por imagen , Riñón/diagnóstico por imagen , Corazón/diagnóstico por imagen , Telemedicina , Femenino , MasculinoRESUMEN
BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirugia , Adulto , Humanos , Carcinoma Hepatocelular/radioterapia , Estudios Retrospectivos , Radiocirugia/efectos adversos , Neoplasias Hepáticas/radioterapia , Selección de PacienteRESUMEN
BACKGROUND: There is a sparsity of data evaluating outcomes of patients with Liver Imaging Reporting and Data System (LI-RADS) (LR)-M lesions. PURPOSE: To compare overall survival (OS) and progression free survival (PFS) between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) meeting LR-M criteria and to evaluate factors associated with prognosis. STUDY TYPE: Retrospective. SUBJECTS: Patients at risk for HCC with at least one LR-M lesion with histologic diagnosis, from 8 academic centers, yielding 120 patients with 120 LR-M lesions (84 men [mean age 62 years] and 36 women [mean age 66 years]). FIELD STRENGTH/SEQUENCE: A 1.5 and 3.0 T/3D T1 -weighted gradient echo, T2 -weighted fast spin-echo. ASSESSMENT: The imaging categorization of each lesion as LR-M was made clinically by a single radiologist at each site and patient outcome measures were collected. STATISTICAL TESTS: OS, PFS, and potential independent predictors were evaluated by Kaplan-Meier method, log-rank test, and Cox proportional hazard model. A P value of <0.05 was considered significant. RESULTS: A total of 120 patients with 120 LR-M lesions were included; on histology 65 were HCC and 55 were iCCA. There was similar median OS for patients with LR-M HCC compared to patients with iCCA (738 days vs. 769 days, P = 0.576). There were no significant differences between patients with HCC and iCCA in terms of sex (47:18 vs. 37:18, P = 0.549), age (63.0 ± 8.4 vs. 63.4 ± 7.8, P = 0.847), etiology of liver disease (P = 0.202), presence of cirrhosis (100% vs. 100%, P = 1.000), tumor size (4.73 ± 3.28 vs. 4.75 ± 2.58, P = 0.980), method of lesion histologic diagnosis (P = 0.646), and proportion of patients who underwent locoregional therapy (60.0% vs. 38.2%, P = 0.100) or surgery (134.8 ± 165.5 vs. 142.5 ± 205.6, P = 0.913). Using multivariable analysis, nonsurgical compared to surgical management (HR, 4.58), larger tumor size (HR, 1.19), and higher MELD score (HR, 1.12) were independently associated with worse OS. DATA CONCLUSION: There was similar OS in patients with LR-M HCC and LR-M iCCA, suggesting that LR-M imaging features may more closely reflect patient outcomes than histology. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Colangiocarcinoma/diagnóstico por imagen , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Conductos Biliares Intrahepáticos , Medios de ContrasteRESUMEN
The liver is a rare site for anastomosing hemangiomas with only a few cases reported that characterize the lesions on magnetic resonance imaging (MRI). These lesions may be underreported due to overlapping features with classic hemangiomas. Anastomosing hemangiomas have a well-defined histological profile and are often diagnosed by biopsy in the setting of atypical imaging features. We report a case of biopsy-proven hepatic anastomosing hemangioma found on a screening MRI for hepatocellular carcinoma in a 52-year-old female with cirrhosis. This lesion initially demonstrated interval growth but has shown no local recurrence in the 2-year surveillance period following microwave ablation.
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Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.
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Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Medios de Contraste , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética/métodos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía/métodosRESUMEN
Our aim was to determine the effect of wearing a surgical mask on the number and type of dictation errors in unedited radiology reports. IRB review was waived for this prospective matched-pairs study in which no patient data was used. Model radiology reports (n = 40) simulated those typical for an academic medical center. Six randomized radiologists dictated using speech-recognition software with and without a surgical mask. Dictations were compared to model reports and errors were classified according to type and severity. A statistical model was used to demonstrate that error rates for all types of errors were greater when masks are worn compared to when they are not (unmasked: 21.7 ± 4.9 errors per 1000 words, masked: 27.1 ± 2.2 errors per 1000 words; adjusted p < 0.0001). A sensitivity analysis was performed, excluding a reader with a large number of errors. The sensitivity analysis found a similar difference in error rates for all types of errors, although significance was attenuated (unmasked: 16.9 ± 1.9 errors per 1000 words, masked: 20.1 ± 2.2 errors per 1000 words; adjusted p = 0.054). We conclude that wearing a mask results in a near-significant increase in the rate of dictation errors in unedited radiology reports created with speech-recognition, although this difference may be accentuated in some groups of radiologists. Additionally, we find that most errors are minor single incorrect words and are unlikely to result in a medically relevant misunderstanding.
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COVID-19 , Sistemas de Información Radiológica , Radiología , Humanos , Máscaras , Estudios Prospectivos , SARS-CoV-2RESUMEN
BACKGROUND: FGFR3-altered urothelial cancer (UC) correlates with a non-T cell-inflamed phenotype and has therefore been postulated to be less responsive to immune checkpoint blockade (ICB). Preclinical work suggests FGFR3 signalling may suppress pathways such as interferon signalling that alter immune microenvironment composition. However, correlative studies examining clinical trials have been conflicting as to whether FGFR altered tumours have equivalent response and survival to ICB in patients with metastatic UC. These findings have yet to be validated in real world data, therefore we evaluated clinical outcomes of patients with FGFR3-altered metastatic UC treated with ICB and investigate the underlying immunogenomic mechanisms of response and resistance. METHODS: 103 patients with metastatic UC treated with ICB at a single academic medical center from 2014 to 2018 were identified. Clinical annotation for demographics and cancer outcomes, as well as somatic DNA and RNA sequencing, were performed. Objective response rate to ICB, progression-free survival, and overall survival was compared between patients with FGFR3-alterations and those without. RNA expression, including molecular subtyping and T cell receptor clonality, was also compared between FGFR3-altered and non-altered patients. RESULTS: Our findings from this dataset confirm that FGFR3-altered (n = 17) and wild type (n = 86) bladder cancers are equally responsive to ICB (12 vs 19%, p = 0.73). Moreover, we demonstrate that despite being less inflamed, FGFR3-altered tumours have equivalent T cell receptor (TCR) diversity and that the balance of a CD8 T cell gene expression signature to immune suppressive features is an important determinant of ICB response. CONCLUSIONS: Our work in a real world dataset validates prior observations from clinical trials but also extends this prior work to demonstrate that FGFR3-altered and wild type tumours have equivalent TCR diversity and that the balance of effector T cell to immune suppression signals are an important determinant of ICB response.
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Carcinoma de Células Transicionales/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos T CD8-positivos/metabolismo , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/inmunología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T/metabolismo , Estudios Retrospectivos , Análisis de Secuencia de ADN , Análisis de Secuencia de ARN , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunologíaRESUMEN
Lymph node metastases from hepatocellular carcinoma (HCC) represents a challenging clinical scenario with a poor prognosis, especially in the setting of prior liver transplant. Long-term survival is achievable in select patients with isolated lymph node metastases who undergo surgical resection, but little data exist regarding non-surgical options. For intrahepatic HCC, stereotactic body radiation therapy (SBRT) has emerged as a standard and effective nonsurgical treatment option. Here, we present three patients (two with prior liver transplant) with isolated lymph node metastases treated with curative intent using SBRT to doses of 30-45 Gy in three to five fractions. Two patients (with follow-up of 27 and 31 months) had a complete or near-complete response and remain cancer-free. One patient had intrahepatic HCC recurrence shortly after SBRT but stable disease in the treated lymph node metastasis at 20 months. Liver function remained excellent after radiation in all three patients, but one patient developed a grade 3 duodenal ulcer at 20 months that resolved with medical management. These cases illustrate the potential utility of SBRT as a non-invasive, definitive treatment option for patients with isolated lymph node metastases from HCC.
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Anemia Aplásica/genética , Cirrosis Hepática/genética , Hígado/patología , Telomerasa/genética , Acortamiento del Telómero , Adulto , Anemia Aplásica/diagnóstico , Biopsia , Análisis Mutacional de ADN , Humanos , Hígado/citología , Hígado/diagnóstico por imagen , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Masculino , Mutación Missense , Síndrome , Telomerasa/metabolismo , Telómero/metabolismo , Tomografía Computarizada por Rayos XRESUMEN
Background The Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA) is used to assess presumed hepatocellular carcinoma (HCC) after local-regional therapy, but its performance has not been extensively assessed. Purpose To assess the performance of LI-RADS version 2018 TRA in the evaluation of HCC after ablation. Materials and Methods In this retrospective study, patients who underwent ablation therapy for presumed HCC followed by liver transplantation between January 2011 and December 2015 at a single tertiary care center were identified. Lesions were categorized as completely (100%) or incompletely (≤99%) necrotic based on transplant histology. Three radiologists assessed pre- and posttreatment MRI findings using LI-RADS version 2018 and the TRA, respectively. Interreader agreement was assessed by using the Fleiss κ test. Performance characteristics for predicting necrosis category based on LI-RADS treatment response (LR-TR) category (viable or nonviable) were calculated by using generalized mixed-effects models to account for clustering by subject. Results A total of 36 patients (mean age, 58 years ± 5 [standard deviation]; 32 men) with 53 lesions was included. Interreader agreement for pretreatment LI-RADS category was 0.40 (95% confidence interval [CI]: 0.15, 0.67; P < .01) and was lower than the interreader agreement for TRA category (κ = 0.71; 95% CI: 0.59, 0.84; P < .01). After accounting for clustering by subject, sensitivity of tumor necrosis across readers ranged from 40% to 77%, and specificity ranged from 85% to 97% when LR-TR equivocal assessments were treated as nonviable. When LR-TR equivocal assessments were treated as viable, sensitivity of tumor necrosis across readers ranged from 81% to 87%, and specificity ranged from 81% to 85% across readers. Six (11%) of 53 treated lesions were LR-TR equivocal by consensus, with most (five of six) incompletely necrotic at histopathology. Conclusion The Liver Imaging Reporting and Data System treatment response algorithm can be used to predict viable or nonviable hepatocellular carcinoma after ablation. Most ablated lesions rated as treatment response equivocal were incompletely necrotic at histopathology. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Do and Mendiratta-Lala in this issue.
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Carcinoma Hepatocelular/diagnóstico por imagen , Ablación por Catéter/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Sistemas de Información Radiológica , Anciano , Algoritmos , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Hígado/diagnóstico por imagen , Hígado/cirugía , Neoplasias Hepáticas/cirugía , Masculino , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Single hepatocellular carcinoma (HCC) tumors can be successfully eradicated with thermal ablation (TA). We assessed the validity of the Liver Imaging Reporting and Data System Treatment Response (LR-TR) criteria with a retrospective analysis of a single-center database of patients with small HCC tumors (<3 cm in diameter) who underwent both laparoscopic TA and liver transplantation (LT) from 2004 to 2018. Postablation MRIs were assigned LR-TR categories (nonviable, equivocal, and viable) for ablated lesions and Liver Imaging Reporting and Data System (LI-RADS) categories (probable or definite HCC) for untreated lesions. Interpretations were compared with the histopathology of the post-LT explanted liver. There were 45 patients with 81 tumors (59 ablated and 22 untreated; mean size, 2.2 cm), and 23 (39%) of the ablated tumors had viable HCC on histopathology. The sensitivity/specificity of LR-TR categories (nonviable/equivocal versus viable) of ablated tumors was 30%/99%, with a positive predictive value (PPV)/negative predictive value (NPV) of 93%/69%. The sensitivity varied with residual tumor size. The sensitivity/specificity of LI-RADS 4 and 5 diagnostic criteria at detecting new HCC was 65%/94%, respectively, with a PPV/NPV of 85%/84%. The interrater reliability (IRR) was high for LR-TR categories (90% agreement, Cohen's ĸ = 0.75) and for LI-RADS LR-4 and LR-5 diagnostic categories (91% agreement, Cohen's ĸ = 0.80). In patients with HCC <3 cm in diameter, LR-TR criteria after TA had high IRR but low sensitivity, suggesting that the LR-TR categories are precise but inaccurate. The low sensitivity may be secondary to TA's disruption in the local blood flow of the tissue, which could affect the arterial enhancement phase on MRI. Additional investigation and new technologies may be necessary to improve imaging after ablation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Medios de Contraste , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/efectos adversos , Imagen por Resonancia Magnética , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Cesarean scar ectopic pregnancies are a rare form of extrauterine pregnancies, yet their incidence is increasing given the rise in cesarean deliveries. Similar to other ectopic pregnancies, cesarean scar ectopic pregnancies pose a great risk for maternal hemorrhage and ultimately maternal mortality. This study presents the case of a cesarean scar ectopic pregnancy in a patient with 3 prior cesarean deliveries. Here, we highlight the importance of early diagnosis and treatment of cesarean scar ectopic pregnancies.
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There is a constantly evolving knowledgebase regarding the safety of MRI in pregnant patients, as well as the safety of gadolinium administration, given potential fetal risks. This review provides an overview of national and international recommendations for patient screening and safety by trimester, evaluates the most recent literature regarding administration of gadolinium in pregnant patients, and discusses technical requirements when imaging pregnant patients. A protocol for imaging pregnant patients is provided, and multiple common indications for MRI in pregnancy are discussed. Level of Evidence 5. Technical Efficacy Stage 5. J. Magn. Reson. Imaging 2019;49:621-631.
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Imagen por Resonancia Magnética , Embarazo , Dolor Abdominal/complicaciones , Dolor Abdominal/diagnóstico por imagen , Desprendimiento Prematuro de la Placenta/diagnóstico por imagen , Enfermedades de los Anexos/complicaciones , Enfermedades de los Anexos/diagnóstico por imagen , Apendicitis/complicaciones , Apendicitis/diagnóstico por imagen , Medios de Contraste/efectos adversos , Femenino , Gadolinio/efectos adversos , Humanos , Leiomioma/complicaciones , Leiomioma/diagnóstico por imagen , Seguridad del Paciente , Enfermedades Placentarias/diagnóstico por imagen , Complicaciones del Embarazo/diagnóstico por imagen , Complicaciones del Embarazo/prevención & control , Diagnóstico Prenatal/métodos , Urolitiasis/complicaciones , Urolitiasis/diagnóstico por imagen , Rotura Uterina/diagnóstico por imagenRESUMEN
We present the case of a 24-year-old woman with morbid obesity who came to the emergency department with right upper quadrant abdominal pain associated with nausea and vomiting. Her workup included a right upper quadrant ultrasound suggestive of a small gallbladder with cholelithiasis without sonographic evidence of acute cholecystitis. She underwent attempted laparoscopic cholecystectomy with no identifiable gallbladder during surgery. Postsurgical cross-sectional imaging confirmed gallbladder agenesis. This case provides an example of a rare but convincing clinical and radiologic mimic of cholelithiasis. In certain cases of biliary colic and imaging revealing a small gallbladder, a magnetic resonance cholangiopancreatography may be warranted to evaluate gallbladder agenesis and avoid unnecessary surgery.
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PURPOSE: Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported. We hypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. PATIENTS AND METHODS: We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti-programmed death-ligand 1 antibody, atezolizumab. RESULTS: Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability (MSH2 and MSH6) and hypermutation (POLE). A patient with an MSH6 mutation was treated with immune checkpoint blockade, which resulted in stable disease. CONCLUSION: Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level of RNA expression, are the first report, to our knowledge, of MSH2 and MSH6 mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor.