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Benign vulvar lesions can be difficult to differentiate with few publications on their imaging appearances. While many vulvar lesions may be clinically diagnosed and treated, more are being detected incidentally with the increasing prevalence of magnetic resonance imaging (MRI) of the pelvis. In addition, clinicians may find imaging of benign vulvar lesions helpful for greater anatomical correlation. After reviewing the important MRI sequences for vulvar imaging and the anatomy of the vulva on MRI, this pictorial essay illustrates variety of cystic and solid benign vulvar lesions to familiarize radiologists with their common MRI appearances. Other miscellaneous pelvic lesions that can affect the vulva are also described.
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Prior studies on contrast-enhanced ultrasound (CEUS) lymphography for preoperative mapping before lymphaticovenous anastomosis surgery in patients with extremity lymphedema have been limited to using only Lumason and Sonazoid as microbubble contrast agents. The purpose of this study was to determine the feasibility of using two other Food & Drug Administration-approved microbubble agents, Optison and Definity, for imaging lymphatic vessels in the upper extremities. Nine female adults with unilateral upper extremity lymphedema anticipating lymphaticovenous anastomosis surgery underwent CEUS lymphography of the unaffected upper extremity randomized to either Lumason, Definity, or Optison. Lymphatic vessels were visualized in all but one case when undilated Definity was used. In the eight upper extremities where lymphatic vessels were visualized, an average of eight intradermal injections of microbubbles were performed in the extremity. Lymphatic vessels could be identified in 57% (36 of 63) of the injections. The effective dilution for each of the microbubble agents is provided. This was the first successful demonstration of lymphatic vessel visualization using either Definity or Optison. Broadening the range of available microbubble agents for CEUS lymphography could improve accessibility to the procedure and provide potentially safer alternatives.
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Diverticular disease is a major cause of hospitalizations, especially in the elderly. Although diverticulosis and its complications predominately affect the colon, the formation of diverticula in the small intestine, most commonly in the duodenum, is well characterized in the literature. Although small bowel diverticula are typically asymptomatic, and diagnosed incidentally, a complication of periampullary duodenal diverticulum is Lemmel syndrome. Lemmel syndrome is an extremely rare condition whereby periampullary duodenal diverticula, most commonly without diverticulitis, leads to obstruction of the common bile duct due to mass effect and associated complications including acute cholangitis and pancreatitis. Here, we present the first case, to our knowledge, of periampullary duodenal diverticulitis complicated by Lemmel syndrome with concomitant colonic diverticulitis with colovesical fistula. Our case and literature review emphasizes that Lemmel syndrome can present with or without suggestions of obstructive jaundice and can most often be managed conservatively if caught early, except in the setting of emergent complications.
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Enfermedades Duodenales , Humanos , Enfermedades Duodenales/complicaciones , Tomografía Computarizada por Rayos X , Masculino , Anciano , Fístula Intestinal/complicaciones , Fístula Intestinal/etiología , Diverticulitis del Colon/complicaciones , Femenino , Enfermedades del Sigmoide/complicaciones , Enfermedades del Sigmoide/etiología , Diverticulitis/complicacionesRESUMEN
OBJECTIVES: To assess the safety, technical success, disease progression, and survival associated with percutaneous image-guided cryoablation of renal cell carcinoma metastasis (mRCC) in the adrenal gland. METHODS: Retrospective, single-institution review of adult patients undergoing percutaneous cryoablation for adrenal mRCC between the years of 2007-2021. Technical parameters, technical success, safety, and survival were analyzed according to standard criteria. RESULTS: Forty-six patients (39 male; mean age 66 ± 8.8 years) with 57 tumors ablated over 51 sessions with a median hospital length of stay of 1 day (range 0-3 days). Forty-four (96%) had primary of clear cell histology. Aim of ablation was curative intent in 39 of 57 tumors (72%) with local tumor control in the remainder. There were 2 (4%) technical failures and technique efficacy was achieved in 52 out of the remaining 55 (95%). There were no Common Terminology Criteria for Adverse Events' immediate complications and 4 of 51 (8%) delayed complications. Twenty-five of 57 (44%) had disease progression anywhere, away from ablation site. One-, 3-, and 5-year recurrence free survival rates were 100%, 89%, and 89% and overall survival was 98%, 85%, and 71%. Fifty-one of 57 (89%) underwent preprocedural alpha blockade with hypertensive crisis in 27 of 56 (54%) available records, of which there were no adverse outcomes. CONCLUSION: Percutaneous cryoablation of mRCC to the adrenal glands is safe with robust local control, leading to advocacy for its ongoing use in this patient population. Multi-disciplinary management is recommended for successful treatment.
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Neoplasias de las Glándulas Suprarrenales , Carcinoma de Células Renales , Criocirugía , Neoplasias Renales , Adulto , Humanos , Masculino , Lactante , Carcinoma de Células Renales/cirugía , Neoplasias Renales/patología , Criocirugía/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de las Glándulas Suprarrenales/etiología , Progresión de la EnfermedadRESUMEN
Lymphaticovenous anastomosis (LVA) surgery is an effective surgery for the treatment of lymphedema in the extremities. Indocyanine green lymphography is the reference standard for visualizing lymphatics for LVA surgery, but it has several limitations; most notably, superficial dermal congestion can mask deeper lymphatic vessels. To overcome the limitations, we add contrast-enhanced ultrasound (CEUS) lymphography. We have previously reported that CEUS lymphography can identify lymphatic vessels for LVA surgery that indocyanine green lymphography does not. Here, we describe how we perform CEUS lymphography, including workflow, technique, and documentation. Before informed consent, the patient must be screened for possible adverse reactions to microbubbles. The procedure involves multiple intradermal injections of the microbubble agent at various sites along the extremity. After each injection, imaging for microbubble uptake by lymphatic vessels is performed using an ultrasound scanner with contrast-specific software. We use sulfur hexafluoride lipid-type A microspheres (Lumason/SonoVue; Bracco Suisse SA), but we are investigating the performance of other Food & Drug Administration-approved microbubble agents for CEUS lymphography. Having a systematic approach to marking the skin can mitigate the hindrance of marking over ultrasound coupling gel. Another benefit of CEUS lymphography is the rapid identification of neighboring veins compatible in size and location for anastomosis. We hold regular scheduled multidisciplinary meetings for coordination of care, discussion of outcomes, quality assurance, and ongoing innovation.
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Purpose: To develop, test, and validate a deep learning (DL) tool that improves upon a previous feature-based CT image processing bone mineral density (BMD) algorithm and compare it against the manual reference standard. Materials and Methods: This single-center, retrospective, Health Insurance Portability and Accountability Act-compliant study included manual L1 trabecular Hounsfield unit measurements from abdominal CT scans in 11 035 patients (mean age, 58 years ± 12 [SD]; 6311 women) as the reference standard. Automated level selection and L1 trabecular region of interest (ROI) placement were then performed in this CT cohort with both a previously validated feature-based image processing tool and a new DL tool. Overall technical success rates and agreement with the manual reference standard were assessed. Results: The overall success rate of the DL tool in this heterogeneous patient cohort was significantly higher than that of the older image processing BMD algorithm (99.3% vs 89.4%, P < .001). Using this DL tool, the closest median Hounsfield unit values for single-, three-, and seven-slice vertebral ROIs were within 5% of the manual reference standard Hounsfield unit values in 35.1%, 56.9%, and 85.8% of scans; within 10% in 56.6%, 75.6%, and 92.9% of scans; and within 25% in 76.5%, 89.3%, and 97.1% of scans, respectively. Trade-offs in sensitivity and specificity for osteoporosis assessment were observed from the single-slice approach (sensitivity, 39.4%; specificity, 98.3%) to the minimum value of the multislice approach (for seven contiguous slices; sensitivity, 71.3% and specificity, 94.6%). Conclusion: The new DL BMD tool demonstrated a higher success rate than the older feature-based image processing tool, and its outputs can be targeted for higher specificity or sensitivity for osteoporosis assessment.Keywords: CT, CT-Quantitative, Abdomen/GI, Skeletal-Axial, Spine, Deep Learning, Machine Learning Supplemental material is available for this article. © RSNA, 2022.
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Background Lymphaticovenous anastomosis (LVA) surgery is an effective surgical treatment of secondary lymphedema in the extremities, but indocyanine green (ICG) fluorescent lymphography, the reference standard for imaging target lymphatic vessels, has several limitations. More effective methods are needed for preoperative planning. Purpose To evaluate whether contrast-enhanced US (CEUS) can be used to identify target lymphatic vessels for LVA surgery in patients with secondary upper extremity lymphedema and compare the results with those from ICG fluorescent lymphography. Materials and Methods In this single-center retrospective review, CEUS with intradermal injection of microbubbles was performed in patients before LVA surgery in the upper extremities between October 2019 and September 2021. All patients had secondary upper extremity lymphedema from breast cancer treatment. Technical success rate was defined as lymphatic vessels identified with use of CEUS that led to successful LVAs. Descriptive statistics were used. Results All 11 patients were women (mean age, 56 years ± 8 [SD]). The median number of microbubble injection sites was 11 (range, 8-14). CEUS helped identify lymphatic vessels in all 11 women, including in six women in whom ICG fluorescent lymphography could not be performed or failed to help identify any targets. Thirty-five explorations (median, three per patient; range, two to four) were performed, and 24 LVAs (median, three per patient; range, zero to four) were created. Of the anastomoses, 33% (eight of 24) were mapped with use of both CEUS and ICG fluorescent lymphography, 58% (14 of 24) with CEUS only, and 8% (two of 24) with ICG fluorescent lymphography only. Among the 33 explorations on targets mapped with CEUS, an anastomosis could be made at 22 sites, for a technical success rate of 67%. Seven women had at least one additional LVA created from the use of CEUS. Conclusion Contrast-enhanced US is a promising tool for identifying lymphatic vessels in the upper extremities, especially when indocyanine green fluorescent lymphography fails to depict targets or cannot be used. Published under a CC BY 4.0 license.
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Vasos Linfáticos , Linfedema , Anastomosis Quirúrgica/métodos , Colorantes , Femenino , Humanos , Verde de Indocianina , Vasos Linfáticos/diagnóstico por imagen , Vasos Linfáticos/cirugía , Linfedema/diagnóstico por imagen , Linfedema/cirugía , Linfografía/métodos , Masculino , Microburbujas , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE(S): Identifying provider variation in surgical costs could control rising healthcare expenditure and deliver cost-effective care. While these efforts have mostly focused on complex and expensive operations, provider-level variation in costs of thyroidectomy has not been well examined. METHODS: We retrospectively evaluated 921 consecutive total thyroidectomies performed by 14 surgeons at our institution between September 2011 and July 2016. Data were extracted from the Change Healthcare Performance Analytics Program. RESULTS: Mean patient age was 47.4 ± 0.5 y, 81% were females, 64.7% were Caucasians, and 18.8% were outpatients. The number of thyroidectomies performed by the 14 surgeons ranged from 4 to 597 (mean = 66). The mean costs per provider varied widely from $4,293 to $15,529 (P < 0.001). The mean length of stay was 1d ± .03 with wide variation among providers (0-6 d). Providers whose hospital cost exceeded the institutional mean demonstrated significantly higher anesthesia fees and lab costs (P < 0.001). CONCLUSIONS: We found substantial variation in hospital cost among providers for thyroidectomy despite practicing in the same academic institution, with some surgeons spending 3x more for the same operation. Implementing institutional standards of practice could reduce variation and the costs of surgical care.
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Tiroidectomía , Honorarios y Precios , Femenino , Gastos en Salud , Costos de Hospital , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cirujanos/economía , Tiroidectomía/economíaRESUMEN
The outcomes of technically successful image-guided percutaneous thermal ablation of melanoma adrenal metastases involving 11 tumors in 9 consecutive patients over 12 years (2009-2020) were evaluated. All patients had multiple treated metastatic sites, and 44.4% (4/9) had greater than 5 metastatic sites. The mean maximal tumor diameter was 3.6 ± 1.6 cm. The local recurrence-free survival at 1 year was 85.7%. With a median survival of 19.4 months, 66.6% (6/9) of patients died from tumor progression. The 1- and 3-year overall survival rate was 60.0% and 30.0%, respectively. All patients were pretreated with alpha-adrenergic blockade, and 36% (4/11) developed a hypertensive crisis. The median hospital length of stay was 1 day (range, 1-2 days), without any major complications. Thermal ablation of adrenal metastasis from a melanoma provides acceptable local control and a good safety profile.
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Neoplasias de las Glándulas Suprarrenales , Ablación por Catéter , Criocirugía , Melanoma , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/cirugía , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND. COVID-19 vaccination may trigger reactive lymphadenopathy, confounding imaging interpretation. There has been limited systematic analysis of PET findings after COVID-19 vaccination. OBJECTIVE. The purpose of this study was to evaluate the frequency and characteristics of abnormal FDG and 11C-choline uptake on PET performed after COVID-19 vaccination. METHODS. This retrospective study included 67 patients (43 men and 24 women; mean [± SD] age, 75.6 ± 9.2 years) who underwent PET examination between December 14, 2020, and March 10, 2021, after COVID-19 vaccination and who had undergone prevaccination PET examination without visible axillary node uptake. A total of 52 patients received the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech; hereafter referred to as the Pfizer-BioNTech vaccine), and 15 received the SARS-CoV-2 mRNA-1273 vaccine (Moderna; hereafter referred to as the Moderna vaccine). Sixty-six of the patients underwent PET/CT, and one underwent PET/MRI. Fifty-four PET examinations used FDG, and 13 used 11C-choline. PET was performed a median of 13 and 10 days after vaccination for patients who had received one (n = 44) and two (n = 23) vaccine doses, respectively. Two nuclear medicine physicians independently reviewed images and were blinded to injection laterality and the number of days since vaccination. Lymph node or deltoid SUVmax greater than the blood pool SUVmax was considered positive. Interreader agreement was assessed, and the measurements made by the more experienced physician were used for subsequent analysis. RESULTS. Positive axillary lymph node uptake was observed in 10.4% (7/67) of patients (7.4% [4/54] of FDG examinations and 23.1% [3/13] of 11C-choline examinations); of the patients with positive axillary lymph nodes, four had received the Pfizer vaccine, and three had received the Moderna vaccine. Injection laterality was documented for five of seven patients with positive axillary lymph nodes and was ipsilateral to the positive node in all five patients. PET was performed within 24 days of vaccination for all patients with a positive node. One patient showed extraaxillary lymph node uptake (ipsilateral supraclavicular uptake on FDG PET). Ipsilateral deltoid uptake was present in 14.5% (8/55) of patients with documented injection laterality, including 42.9% (3/7) of patients with positive axillary lymph nodes. Interreader agreement for SUV measurements (expressed as intraclass correlation coefficients) ranged from 0.600 to 0.988. CONCLUSION. Increased axillary lymph node or ipsilateral deltoid uptake is occasionally observed on FDG or 11C-choline PET performed after COVID-19 vaccination with the Pfizer-BioNTech or Moderna vaccine. CLINICAL IMPACT. Interpreting physicians should recognize characteristics of abnormal uptake on PET after COVID-19 vaccination to guide optimal follow-up management and reduce unnecessary biopsies.
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Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Músculo Deltoides/diagnóstico por imagen , Linfadenopatía/diagnóstico por imagen , Linfadenopatía/etiología , Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Vacuna nCoV-2019 mRNA-1273 , Anciano , Axila/diagnóstico por imagen , Vacuna BNT162 , Radioisótopos de Carbono/farmacocinética , Colina/farmacocinética , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Masculino , Radiofármacos/farmacocinética , Estudios Retrospectivos , SARS-CoV-2RESUMEN
PURPOSE: To retrospectively evaluate the incidence of carcinoid crisis, other complications, and physiologic disturbances during percutaneous image-guided core needle biopsy of neuroendocrine tumors (NETs) in the lung and the liver. MATERIALS AND METHODS: Between January 2010 and January 2020, 106 computed tomography (CT) or ultrasound (US)-guided core needle biopsies of lung and liver NETs were performed in 95 consecutive adult patients. The mean age was 64 ± 13 years, and 48% were female. The small bowel was the most common primary site (33%, 31/95), and 32 (34%) patients had pre-existing symptoms of carcinoid syndrome. The mean tumor size was 3.2 ± 2.6 cm, and mean number of passes was 3.4 ± 1.6. A 17/18-gauge needle was used in 91% (96/106) of the biopsies. Thirteen (12%) patients received either outpatient or prophylactic octreotide. RESULTS: No patients experienced carcinoid crisis or needed octreotide, inotropes, vasopressors, or resuscitation. A single biopsy procedure (0.9%, 1/106) was complicated by bleeding that required angiographic hepatic artery embolization. Changes in pre-biopsy- versus post-biopsy systolic blood pressure and heart rate were -1.6 mm Hg (P = .390) and 0.6 beat/min (P = .431), respectively. Tumor functional status, overall tumor burden, and the elevation of neuroendocrine markers were not associated with intraprocedural physiologic disturbances. There were 4 minor complications (0.4%, 4/106) associated with the biopsy procedure that were not attributed to hormone excretion from tumor manipulation. CONCLUSIONS: Percutaneous image-guided core biopsy of NETs is safe, with low complication rate and no definite carcinoid crisis in the current cohort.
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Biopsia con Aguja Gruesa/efectos adversos , Biopsia Guiada por Imagen/efectos adversos , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/patología , Síndrome Carcinoide Maligno/epidemiología , Tumores Neuroendocrinos/patología , Radiografía Intervencional/efectos adversos , Ultrasonografía Intervencional/efectos adversos , Anciano , Femenino , Humanos , Incidencia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Síndrome Carcinoide Maligno/diagnóstico , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
Few models exist for studying neuroendocrine tumors (NETs), and there are mounting concerns that the currently available array of cell lines is not representative of NET biology. The lack of stable patient-derived NET xenograft models further limits the scientific community's ability to make conclusions about NETs and their response to therapy in patients. To address these limitations, we propose the use of an ex vivo 3D flow-perfusion bioreactor system for culturing and studying patient-derived NET surrogates. Herein, we demonstrate the utility of the bioreactor system for culturing NET surrogates and provide methods for evaluating the efficacy of therapeutic agents on human NET cell line xenograft constructs and patient-derived NET surrogates. We also demonstrate that patient-derived NET tissues can be propagated using the bioreactor system and investigate the near-infrared (NIR) dye IR-783 for its use in monitoring their status within the bioreactor. The results indicate that the bioreactor system and similar 3D culture models may be valuable tools for culturing patient-derived NETs and monitoring their response to therapy ex vivo.
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Reactores Biológicos/estadística & datos numéricos , Técnicas de Cultivo de Célula/métodos , Neoplasias Intestinales/patología , Neoplasias Pulmonares/patología , Modelos Biológicos , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Neoplasias Gástricas/patología , Neoplasias de la Tiroides/patología , Animales , Humanos , Ratones , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In an effort to discover viable systemic chemotherapeutic agents for neuroendocrine tumors (NETs), we screened a small library of 18 drug-like compounds obtained from the Velu lab against pulmonary (H727) and thyroid (MZ-CRC-1 and TT) neuroendocrine tumor-derived cell lines. Two potent lead compounds (DHN-II-84 and DHN-III-14) identified from this screening were found to be analogs of the natural product makaluvamine. We further characterized the antitumor activities of these two compounds using pulmonary (H727), thyroid (MZ-CRC-1) and pancreatic (BON) neuroendocrine tumor cell lines. Flow cytometry showed a dose-dependent increase in apoptosis in all cell lines. Induction of apoptosis with these compounds was also supported by the decrease in myeloid cell leukemia-1 (MCL-1) and X-chromosome linked inhibitor of apoptosis (XIAP) detected by Western blot. Compound treatment decreased NET markers chromogranin A (CgA) and achaete-scute homolog 1 (ASCL1) in a dose-dependent manner. Moreover, the gene expression analysis showed that the compound treatment reduced c-Kit proto-oncogene expression in the NET cell lines. Induction of apoptosis could also have been caused by the inhibition of c-Kit expression, in addition to the known mechanisms such as damage of DNA by topoisomerase II inhibition for this class of compounds. In summary, makaluvamine analogs DHN-II-84 and DHN-III-14 induced apoptosis, decreased neuroendocrine tumor markers, and showed promising antitumor activity in pulmonary, thyroid, and pancreatic NET cell lines, and hold potential to be developed as an effective treatment to combat neuroendocrine tumors.
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Antineoplásicos/química , Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Tumores Neuroendocrinos/patología , Proteínas Proto-Oncogénicas c-kit/genética , Pirroles/química , Pirroles/farmacología , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Proto-Oncogenes MasAsunto(s)
Infecciones Asintomáticas/epidemiología , Infecciones por Coronavirus/epidemiología , Personal Militar , Medicina Naval , Neumonía Viral/epidemiología , Adulto , Ageusia/fisiopatología , Atención Ambulatoria/estadística & datos numéricos , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Tos/fisiopatología , Brotes de Enfermedades , Femenino , Fiebre/fisiopatología , Cefalea/fisiopatología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Trastornos del Olfato/fisiopatología , Pandemias , Aislamiento de Pacientes , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Cuarentena , SARS-CoV-2 , Navíos , Adulto JovenRESUMEN
PURPOSE/OBJECTIVE(S): To report tumor genomic factors associated with overall survival (OS) and local failure (LF) for patients with colorectal cancer (CRC) who received metastasis-directed stereotactic body radiation therapy (SBRT). MATERIALS/METHODS: This was a retrospective review of patients with CRC who received metastasis-directed SBRT. Tumor genomic alterations were identified through KRAS, BRAF, or a 50-gene next generation sequencing panel. OS and LF were estimated using Kaplan-Meier and competing-risk methods. RESULTS: Eighty-five patients and 109 lesions were treated between 2008 and 2018. The median patient follow-up was 50 months (IQR: 28-107). The median and 5-year OS was 34 months and 26% (95% CI: 16-41%), respectively. The 2-year cumulative incidence of LF was 30% (95% CI: 23-41%). Univariate associates with OS included patient age ≥60 years, bone metastasis, increasing tumor size, KRAS mutation, and combined KRAS and TP53 mutation, while increasing tumor size, bone metastasis, biologically effective dose <100 Gy, and combined KRAS and TP53 mutation were associated with LF. Multivariate associates with OS included patient age ≥60 years (HR: 2.4, 95% CI: 1.2-4.8, p = 0.01), lesion size per 1 cm (HR: 1.3, 95% CI: 1.1-1.5, p < 0.01), and KRAS mutation (HR: 2.2, 95% CI: 1.2-4.3, p < 0.01), while no multivariable model for LF retained more than a single variable. CONCLUSION: Genomic factors, in particular KRAS and TP53 mutation, may assist in patient selection and radiotherapeutic decision-making for patients with oligometastatic CRC. Prospective validation, ideally with genomic correlation of all irradiated metastases, is warranted.
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Neoplasias Colorrectales , Neoplasias Pulmonares , Radiocirugia , Neoplasias Colorrectales/genética , Genómica , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Neuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. We found that histone deacetylase inhibitors can upregulate the functional expression of somatostatin receptor subtype 2. METHODS: We evaluated the effect of histone deacetylase inhibitors on somatostatin receptor subtype 2 expression at the mRNA and protein level in neuroendocrine tumor cell lines. The effect of histone deacetylase inhibitors on surface somatostatin receptor subtype 2 was also investigated by fluorescence-activated cell sorting analysis. Changes in somatostatin receptor subtype 2 expression in neuroendocrine tumor xenografts after treatment were imaged using Ga68-DOTATATE positron emission tomography/computed tomography. RESULTS: The functional increase of somatostatin receptor subtype 2 in neuroendocrine tumors after histone deacetylase inhibitor treatment was confirmed through in vitro experiments and small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging. Histone deacetylase inhibitors increased somatostatin receptor subtype 2 transcription and protein expression in neuroendocrine tumor cell lines. Small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging confirmed the enhancement of radiopeptide uptake after histone deacetylase inhibitor administration. CONCLUSION: This study demonstrates a new method to potentially improve imaging and treatments that target somatostatin receptor subtype 2 in neuroendocrine tumors.
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Inhibidores de Histona Desacetilasas/administración & dosificación , Imagen Molecular/métodos , Tumores Neuroendocrinos/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Receptores de Somatostatina/metabolismo , Animales , Línea Celular Tumoral , Separación Celular , Depsipéptidos/administración & dosificación , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Tumores Neuroendocrinos/patología , Compuestos Organometálicos/administración & dosificación , Páncreas/diagnóstico por imagen , Páncreas/patología , Neoplasias Pancreáticas/patología , Análisis de Matrices Tisulares , Transcripción Genética/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Background Abdominal and thoracic CT provide a valuable opportunity for osteoporosis screening regardless of the clinical indication for imaging. Purpose To establish reference normative ranges for first lumbar vertebra (L1) trabecular attenuation values across all adult ages to measure bone mineral density (BMD) at routine CT. Materials and Methods Reference data were constructed from 20 374 abdominal and/or thoracic CT examinations performed at 120 kV. Data were derived from adults (mean age, 60 years ± 12 [standard deviation]; 56.1% [11 428 of 20 374] women). CT examinations were performed with (n = 4263) or without (n = 16 111) intravenous contrast agent administration for a variety of unrelated clinical indications between 2000 and 2018. L1 Hounsfield unit measurement was obtained either with a customized automated tool (n = 11 270) or manually by individual readers (n = 9104). The effects of patient age, sex, contrast agent, and manual region-of-interest versus fully automated L1 Hounsfield unit measurement were assessed using multivariable logistic regression analysis. Results Mean L1 attenuation decreased linearly with age at a rate of 2.5 HU per year, averaging 226 HU ± 44 for patients younger than 30 years and 89 HU ± 38 for patients 90 years or older. Women had a higher mean L1 attenuation compared with men (P < .008) until menopause, after which both groups had similar values. Administration of intravenous contrast agent resulted in negligible differences in mean L1 attenuation values except in patients younger than 40 years. The fully automated method resulted in measurements that were average 21 HU higher compared with manual measurement (P < .004); at intrapatient subanalysis, this difference was related to the level of transverse measurement used (midvertebra vs off-midline level). Conclusion Normative ranges of L1 vertebra trabecular attenuation were established across all adult ages, and these can serve as a quick reference at routine CT to identify adults with low bone mineral density who are at risk for osteoporosis. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Smith in this issue.