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1.
Gastrointest Endosc ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729313

RESUMO

BACKGROUND AND AIMS: Emerging data suggest neoadjuvant chemotherapy (NAC) for resectable pancreatic ductal adenocarcinoma (PDAC) is associated with improved survival. However, less than 40% demonstrate a meaningful radiographic response to NAC. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a new modality to treat PDAC. We hypothesize that NAC plus EUS-RFA can be used in the management of resectable PDAC. METHODS: Prospective review of PDAC patients meeting criteria of resectable tumor anatomy that underwent NAC chemotherapy plus EUS-RFA followed by pancreatic resection. Radiographic imaging, perioperative and short-term outcomes were recorded. Surgical pathology specimens were analyzed for treatment response. RESULTS: Three eligible patients with resectable PDAC received 4 months of NAC plus EUS-RFA. One month after NAC and EUS-RFA completion, all 3 patients underwent standard pancreaticoduodenectomy without complications. After a 6-week recovery, all patients completed 2 months of post-op adjuvant chemotherapy. CONCLUSIONS: In our institutional experience, this treatment protocol appears safe as patients tolerated the combination of chemotherapy and ablation. Patients underwent pancreatic resection with uneventful recovery. This novel neoadjuvant approach may provide a more effective alternative to chemotherapy alone.

2.
Radiology ; 296(1): 76-84, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32315265

RESUMO

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Sistemas de Informação em Radiologia , Idoso , Estudos Transversais , Humanos , Masculino , Valor Preditivo dos Testes , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sociedades Médicas
3.
Radiographics ; 40(5): 1240-1262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32795239

RESUMO

Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show characteristic clinical, histomorphologic, and prognostic features; genetic alterations; and biologic behavior. Up to 10% of panNENs develop in patients with syndromes that predispose them to cancer, such as multiple endocrine neoplasia type 1, von Hippel-Lindau disease, tuberous sclerosis complex, neurofibromatosis type 1, and glucagon cell adenomatosis. PanNENs are classified as either functioning tumors, which manifest early because of clinical symptoms related to increased hormone production, or nonfunctioning tumors, which often manifest late because of mass effect. PanNENs are histopathologically classified as well-differentiated pancreatic neuroendocrine tumors (panNETs) or poorly differentiated pancreatic neuroendocrine carcinomas (panNECs) according to the 2010 World Health Organization (WHO) classification system. Recent advances in cytogenetics and molecular biology have shown substantial heterogeneity in panNECs, and a new tumor subtype, well-differentiated, high-grade panNET, has been introduced. High-grade panNETs and panNECs are two distinct entities with different pathogenesis, clinical features, imaging findings, treatment options, and prognoses. The 2017 WHO classification system and the eighth edition of the American Joint Committee on Cancer staging system include substantial changes. Multidetector CT, MRI, and endoscopic US help in anatomic localization of the primary tumor, local-regional spread, and metastases. Somatostatin receptor scintigraphy and fluorine 18-fluorodeoxyglucose PET/CT are helpful for functional and metabolic assessment. Knowledge of recent updates in the pathogenesis, classification, and staging of panNENs and familiarity with their imaging findings allow optimal patient treatment. ©RSNA, 2020.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Diagnóstico Diferencial , Humanos , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Prognóstico
4.
Radiographics ; 39(7): 2003-2022, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31697623

RESUMO

The pelvic floor is a complex structure that supports the pelvic organs and provides resting tone and voluntary control of the urethral and anal sphincters. Dysfunction of or injury to the pelvic floor can lead to gastrointestinal, urinary, and sexual dysfunction. The prevalence of pelvic floor disorders is much lower in men than in women, and because of this, the majority of the published literature pertaining to MRI of the pelvic floor is oriented toward evaluation of the female pelvic floor. The male pelvic floor has sex-specific differences in anatomy and pathophysiologic disorders. Despite these differences, static and dynamic MRI features of these disorders, specifically gastrointestinal disorders, are similar in both sexes. MRI and MR defecography can be used to evaluate anorectal disorders related to the pelvic floor. MRI can also be used after prostatectomy to help predict the risk of postsurgical incontinence, to evaluate postsurgical function by using dynamic voiding MR cystourethrography, and subsequently, to assess causes of incontinence treatment failure. Increased tone of the pelvic musculature in men secondary to chronic pain can lead to sexual dysfunction. This article reviews normal male pelvic floor anatomy and how it differs from the female pelvis; MRI techniques for imaging the male pelvis; and urinary, gastrointestinal, and sexual conditions related to abnormalities of pelvic floor structures in men.Online supplemental material is available for this article.©RSNA, 2019.


Assuntos
Imageamento por Ressonância Magnética/métodos , Distúrbios do Assoalho Pélvico/diagnóstico por imagem , Diafragma da Pelve/diagnóstico por imagem , Canal Anal/diagnóstico por imagem , Defecografia , Gastroenteropatias/diagnóstico por imagem , Genitália Masculina/diagnóstico por imagem , Humanos , Ligamentos/diagnóstico por imagem , Masculino , Diafragma da Pelve/anatomia & histologia , Complicações Pós-Operatórias/diagnóstico por imagem , Prostatectomia , Doenças Retais/diagnóstico por imagem , Caracteres Sexuais , Disfunções Sexuais Fisiológicas/diagnóstico por imagem , Transtornos Urinários/diagnóstico por imagem
5.
J Surg Res ; 224: 97-101, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29506858

RESUMO

BACKGROUND: Previous studies suggest that agreement between readers of computed tomography (CT) scans for the diagnosis of a ventral hernia (VH) is poor (32% agreement, κ = 0.21). Recommendations were developed by surgeons and radiologists after determining common reasons for disagreement among CT reviewers; however, the long-term effect of adoption of these recommendations has not been assessed. The aim of this quality improvement (QI) project was to determine whether the incorporation of recommendations developed by surgeons and radiologists improves agreement among reviewers of CT scans in diagnosing a VH. METHODS: A prospective cohort of patients, with a CT scan of the abdomen and pelvis in the past 1 y, attending a surgery clinic at a single institution was enrolled. Enrolled subjects underwent a standardized physical examination by a trained hernia surgeon to determine the likelihood of a clinical VH (no, indeterminate, or yes). The QI intervention was the distribution and implementation of previously described recommendations. After a year of intervention, independent radiologists assessed patients' CT scans for the presence or absence of a VH. Percent agreement and kappa were calculated to determine interobserver reliability. In-person discussion on scans with disagreement was held, and the results were used as a "gold standard" to calculate sensitivity, specificity, positive, and negative predictive values for CT scan diagnosis of a VH. RESULTS: A total of 79 patients were included in the study. After QI intervention, seven radiologists agreed on 43% of the scans, and κ was 0.50 (P < 0.001). Agreement was highest among patients with a high clinical likelihood of a VH and lowest among patients with an indeterminate clinical likelihood. Sensitivity and specificity were 0.369 and 0.833, respectively. CONCLUSIONS: After the implementation of recommendations, there is improved agreement among radiologists reading CT scans for the diagnosis of a VH. However, there is substantial room for improvement, and CT scans for the diagnosis of VH is not ready for widespread use.


Assuntos
Hérnia Ventral/diagnóstico por imagem , Melhoria de Qualidade , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Radiographics ; 36(5): 1390-407, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27618321

RESUMO

Life expectancies for solid organ recipients as well as graft survival rates for these patients have improved over the years because of advanced immunosuppressive therapies; however, with chronic use of these drugs, posttransplant malignancy has become one of the leading causes of morbidity for them. The risk of carcinogenesis in transplant recipients is significantly higher than for the general population and cancers tend to manifest at an advanced stage. Posttransplant malignancies are thought to develop by three mechanisms: de novo development, donor-related transmission, and recurrence of a recipient's pretransplant malignancy. Although nonmelanoma skin cancer, Kaposi sarcoma, posttransplant lymphoproliferative disorder, anogenital cancer, and lung cancer are malignancies that are thought to arise de novo, malignant melanoma and cancers that arise in the renal allograft are frequently donor related. Hepatocellular carcinomas and cholangiocarcinomas have a greater tendency to recur in liver transplant recipients. An altered or deranged immune system caused by chronic immunosuppression is considered to be one of the major contributing factors to carcinogenesis. The proposed pathogenic mechanisms for oncogenesis include impaired immunosurveillance of neoplastic cells, weakened immune activity against oncogenic viruses, and direct carcinogenic effects of immunosuppressive agents. Imaging plays an important role in screening, follow-up, and long-term surveillance in patients with malignancies because key imaging features can guide in their timely diagnosis. However, some benign entities such as transplant-related renal fibrosis, biliary necrosis, and infectious nodules in the lungs mimic malignancies and require pathologic confirmation. Management strategies that can improve malignancy-related morbidity and mortality in transplant recipients include prevention of risk factors, appropriate modulation of immunosuppressive agents, prophylaxis against infection-related malignancies, and use of intensive targeted screening programs. (©)RSNA, 2016.


Assuntos
Terapia de Imunossupressão/efeitos adversos , Neoplasias/diagnóstico por imagem , Neoplasias/etiologia , Transplante de Órgãos/efeitos adversos , Humanos , Neoplasias/epidemiologia , Fatores de Risco , Fatores de Tempo
7.
Clin Nucl Med ; 48(9): e452-e454, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37482671

RESUMO

ABSTRACT: 68 Ga-DOTATATE PET/CT is a highly sensitive and specific imaging modality in detecting neuroendocrine tumors. False-positive DOTATATE uptake poses diagnostic challenges. False-positive uptake in a uterine fibroid is the third most common location. We report the case of a 45-year-old woman with clinical concern for possible neuroendocrine tumor showing moderate focal DOTATATE uptake, which was initially thought of to be localized to mesentery on PET/CT images but was subsequently localized to a subserosal uterine fibroid following MRI. Patient underwent hysterectomy, further confirming that the uterine myometrial uptake is within the subserosal fibroid.


Assuntos
Leiomioma , Tumores Neuroendócrinos , Compostos Organometálicos , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tomografia por Emissão de Pósitrons , Leiomioma/diagnóstico por imagem
8.
J Hematol ; 11(6): 216-222, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36632578

RESUMO

Autoimmune hepatitis (AIH) is a rare immune-mediated disease predominantly seen in women and triggered by various environmental factors. Rarely, AIH can be triggered by an underlying malignancy. We report a woman in her 60s who presented with markedly abnormal liver biochemical tests. Serology was positive for anti-smooth muscle antibodies and a liver biopsy confirmed AIH. During the hospital course, she developed sepsis and acute renal failure requiring dialysis support. Serum protein electrophoresis (SPEP) showed a monoclonal IgG kappa protein of 1.92 g/dL and a bone marrow biopsy revealed 7% clonal plasma cells. She had lytic lesions on skeletal survey confirming the diagnosis of a coexisting multiple myeloma (MM). Given her markedly abnormal liver chemistries, we decided to treat the AIH first and use the steroids (an important anti-myeloma therapy) as a bridge to the specific treatment of the MM once her clinical condition improved. She was treated with oral prednisone and azathioprine for AIH. One month later, a marked improvement in liver biochemical test results was noted and she was started on oral ixazomib, lenalidomide and dexamethasone. She received palliative radiotherapy to the lumbar spine (L2), left femur, and ischium lesions. This case highlights a rare co-occurrence of AIH and MM, the underlying mechanism of which is unknown.

9.
Minerva Urol Nephrol ; 74(5): 581-589, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33439577

RESUMO

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.


Assuntos
Neoplasias da Próstata , Biomarcadores , Consenso , Técnica Delphi , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Inquéritos e Questionários
10.
Abdom Radiol (NY) ; 45(12): 4097-4108, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32902658

RESUMO

Over the past decade, there has been a dramatic increase in the number of patients undergoing prostate MRI scans. Patients presenting for prostate MRI are an ageing population and may present with a variety of passive or active implants and devices. These implants and devices can be MR safe or MR conditional or MR unsafe. Patients with certain MR-conditional active implants and devices can safely obtain prostate MRI in a specified MR environment within specific MR imaging parameters. Prostate MRI and PET-MRI in patients with passive implants such as hip prostheses, fiducial markers for SBRT, brachytherapy seeds and prostatectomy bed clips have unique concerns for image optimization that can cause geometric distortion of the diffusion-weighted imaging (DWI) sequence. We discuss strategies to overcome these susceptibility artifacts. Prostate MRI in patients with MR conditional active implants such as cardiac implantable electronic devices (CIED) also require modification of imaging parameters and magnet strength. In this setting, a diagnostic quality prostate MRI can be performed at a lower magnet strength (1.5 T) along with modification of imaging parameters to ensure patient safety. Imaging strategies to minimize susceptibility artifact and decrease the specific absorption rate (SAR) in both settings are described. Knowledge of MR safety considerations and imaging strategies specific to prostate MRI and PET-MRI in patients with implants and devices is essential to ensure diagnostic-quality MR images and patient safety.


Assuntos
Imageamento por Ressonância Magnética , Próstata , Artefatos , Imagem de Difusão por Ressonância Magnética , Humanos , Masculino , Próstata/diagnóstico por imagem , Prostatectomia
11.
Eur J Med Res ; 25(1): 55, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148331

RESUMO

BACKGROUND: Chylothorax is a rare complication of pediatric cardiac operations that occurs more frequently in children with Noonan syndrome, a genetic disorder associated with cardiac defects and lymphatic anomalies. CASE PRESENTATION: We report a case of postoperative chylothorax in a 6-month-old infant with Noonan syndrome where multimodality lymphatic imaging guided management was followed. Drainage patterns of the lymphatic capillaries in the lower and upper extremities were visualized during near-infrared fluorescence lymphatic imaging (NIRFLI). Dynamic magnetic resonance lymphangiography (MRL) further identified the site of leakage in the thoracic duct and subsequently guided surgical intervention. CONCLUSIONS: Application of multimodality imaging allows for greater individualization of treatment and should be considered in patients with complex cases such as those with syndromes associated with a higher incidence of chylothorax. IRB Number: HSC-MS-13-0754, December 10, 2013.


Assuntos
Quilotórax/diagnóstico por imagem , Imagem Multimodal/métodos , Síndrome de Noonan/diagnóstico por imagem , Síndrome de Noonan/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Feminino , Humanos , Lactente , Vasos Linfáticos/diagnóstico por imagem , Linfedema/complicações , Linfedema/diagnóstico por imagem , Linfografia/métodos , Síndrome de Noonan/complicações
12.
Acad Radiol ; 27(11): 1641-1646, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31848074

RESUMO

RATIONALE AND OBJECTIVES: Peer learning is a case-based group-learning model intended to improve performance. In this descriptive paper, we describe multi-institutional, multi-subspecialty, web-based radiology case conferences and summarize the participants' experiences. MATERIALS AND METHODS: A semi-structured, 27-question survey was administered to radiologists participating in abdominal, cardiothoracic, and musculoskeletal case conferences. Survey questions included demographics, perceived educational value and challenges experienced. Survey question formats were continuous, binary, five-point Likert scale or text-based. The measures of central tendencies, proportions of responses and patterns were tabulated. RESULTS: From 57 responders, 12/57 (21.1%) were abdominal, 16/57 (28.1%) were cardiothoracic, and 29/57 (50.8%) were musculoskeletal conference participants; 50/56 (89.3%) represented academic practice. Median age was 45 years (range 35-74); 43/57 (75.4%) were male. Geographically, 16/52 (30.8%) of participants were from the East Coast, 16/52 (30.8%) Midwest, 18/52 (34.6%) West Coast, and 2/52 (3.8%) International. The median reported educational value was 5/5 (interquartile range 5-5). Benefits of the case conference included education (50/95, 52.6%) and networking (39/95, 41.1%). Participants reported presenting the following cases: "great call" 32/48 (66.7%), learning opportunity 32/48 (66.7%), new knowledge 41/49 (83.7%), "zebras" 46/49 (93.9%), and procedural-based 16/46 (34.8%). All 51/51 (100%) of responders reportedly gained new knowledge, 49/51 (96.1%) became more open to group discussion, 34/51 (66.7%) changed search patterns, and 50/51 (98%) would continue to participate. Reported challenges included time zone differences and support from departments for a protected time to participate. CONCLUSION: Peer learning through multi-institutional case conferences provides educational and networking opportunities. Current challenges and desires include having department-supported protected time and ability to receive continuing medical education credit.


Assuntos
Radiologia , Adulto , Idoso , Educação Médica Continuada , Humanos , Internet , Aprendizagem , Masculino , Pessoa de Meia-Idade , Radiologistas , Radiologia/educação
13.
Semin Nucl Med ; 37(6): 429-39, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17920350

RESUMO

Positron emission tomography (PET) using the radiotracer 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) can image cellular proliferation in human cancers in vivo. FLT uptake has been shown to correlate with pathology-based proliferation measurements, including the Ki-67 score, in a variety of human cancers. Unlike pathology-based measurements, imaging-based methods, including FLT-PET, are noninvasive, easily repeatable, and less prone to sampling errors. FLT-PET may therefore be a useful tool for assessing tumor aggressiveness, predicting outcome, planning therapy, or monitoring response to treatment. Three recent clinical studies have reported that FLT-PET can accurately predict response very early after the initiation of chemotherapy. Especially with the advent of cytostatic chemotherapy agents, methods of biologically assessing a tumor's response will take on increasing importance, since changes in tumor size will not always be expected. To date, most studies of FLT-PET have focused on validating it as a means of quantifying cellular proliferation and testing its ability to accurately stage cancer. In some settings, FLT-PET has shown greater specificity for cancer than (18)F-fluorodeoxyglucose (FDG)-PET, which can show false-positive uptake in areas of infection or inflammation. However, because of FLT's lower overall uptake and higher background activity in liver and bone marrow, FLT-PET should not be considered a potential replacement for staging by FLT-PET. Instead, FLT-PET should be considered a powerful addition to FDG-PET, providing additional diagnostic specificity and important biological information that could be useful in predicting prognosis, planning treatment, and monitoring response.


Assuntos
Proliferação de Células , Didesoxinucleosídeos , Neoplasias/diagnóstico por imagem , Compostos Radiofarmacêuticos , Didesoxinucleosídeos/síntese química , Radioisótopos de Flúor , Humanos , Neoplasias/patologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/síntese química
14.
Oncotarget ; 7(27): 41612-41621, 2016 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-27223432

RESUMO

BACKGROUND: It has been proposed that resistance to rapalog therapies in renal cell carcinoma (RCC) is due to adaptive switching from mammalian target of rapamycin complex 1 (mTORC1) to mTORC2. OBJECTIVE: To combine phosphoprotein staining and applied biomedical analytics to investigate resistance signatures in patients with metastatic RCC progressing on rapalog therapies. DESIGN: We applied morphoproteomic analysis to biopsy specimens from nine patients with metastatic RCC who continued to show clinical progression of their tumors while being treated with a rapalog. RESULTS: In patients who were on temsirolimus or everolimus at the time of biopsy, a moderate to strong expression of phosphorylated (p)-mTOR (Ser 2448) in the nuclear compartment with concomitant expression of p-Akt (Ser 473) confirmed the mTORC2 pathway. Concomitant moderate to strong nuclear expression of p-ERK 1/2 (Thr202/Tyr204) and p-STAT3 (Tyr705) was confirmed. Histopathologic changes of hypoxic-type coagulative necrosis in 5 cases as well as identification of insulin-like growth factor-1 receptor (IGF-1R) expression and histone methyltransferase EZH2 in all tumors studied suggested that hypoxia also contributed to the resistance signature. Biomedical analytics provided insight into therapeutic options that could target such adaptive and pathogenetic mechanisms. CONCLUSIONS: Morphoproteomics and biomedical analytics confirm mTORC2/Akt as a resistance signature to rapalog therapy in metastatic RCC and demonstrate activation of the prosurvival ERK and STAT3 pathways and involvement of hypoxic pathways that contribute to pathogenesis of such adaptive resistance. These results highlight the need for a novel combinatorial therapeutic approach in metastatic RCC progressing on rapalogs.


Assuntos
Carcinoma de Células Renais , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais , Proteômica/métodos , Transdução de Sinais/efeitos dos fármacos , Sirolimo/análogos & derivados , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Tamanho Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Biologia Computacional/métodos , Progressão da Doença , Ativação Enzimática/efeitos dos fármacos , Everolimo/uso terapêutico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Metástase Neoplásica , Proteína Oncogênica v-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Sirolimo/uso terapêutico , Carga Tumoral/efeitos dos fármacos
15.
JAMA Surg ; 151(1): 7-13, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26398884

RESUMO

IMPORTANCE: Physical examination misses up to one-third of ventral hernia recurrences seen on radiologic imaging. However, tests such as computed tomographic (CT) imaging are subject to interpretation and require validation of interobserver reliability. OBJECTIVE: To determine the interobserver reliability of CT scans for detecting a ventral hernia recurrence among surgeons and radiologists. We hypothesized there would be significant disagreement in the diagnosis of a ventral hernia recurrence among different observers. Our secondary aim was to determine reasons for disagreement in the interpretation of CT scans. DESIGN, SETTING, AND PARTICIPANTS: One hundred patients who underwent ventral hernia repair from 2010-2011 at an academic health care center with a postoperative CT scan were randomly selected from a larger cohort. This study was conducted from July 2014 to March 2015. Prospective assessment of the presence or absence of a recurrent ventral hernia on CT scans was compared among 9 blinded reviewers and the radiology report. Five reviewers (consensus group) met to discuss all CT scans with disagreement. The discussion was assessed for keywords and key concepts. The remaining 4 reviewers (validation group) read the consensus group recommendations and reassessed the CT scans. Pre- and post-review κ were calculated; the post-review assessments were compared with clinical examination findings. MAIN OUTCOMES AND MEASURES: Interobserver reliability in determining hernia recurrence radiographically. RESULTS: Of 100 CT scans, there was disagreement among all 9 reviewers and the radiology report on the presence/absence of a ventral hernia in 73 cases (κ = 0.44; 95% CI, 0.35-0.54; P < .001). Following discussion among the consensus group, there remained disagreement in 10 cases (κ = 0.91; 95% CI, 0.83-0.95; P < .001). Among the validation group, the κ value had a slight improvement from 0.21 (95% CI, 0.12-0.33) to 0.34 (95% CI, 0.23-0.46) (P < .001) after reviewing the consensus group proposals. There was disagreement between clinical examination and the consensus group assessment of CT scans on the presence/absence of a ventral hernia in 25 cases. The concepts most frequently discussed were the absence of an accepted definition for a radiographic ventral hernia and differentiating pseudorecurrence from recurrence. CONCLUSIONS AND RELEVANCE: Owing to the high interobserver variability, CT scan was not associated with reliable diagnosing in ventral hernia recurrence. Consensus guidelines and improved communication between surgeon and radiologist may decrease interobserver variability.


Assuntos
Hérnia Ventral/diagnóstico por imagem , Variações Dependentes do Observador , Tomografia Computadorizada por Raios X , Comunicação , Humanos , Estudos Prospectivos , Radiologia , Recidiva , Reoperação , Reprodutibilidade dos Testes , Método Simples-Cego , Cirurgiões , Terminologia como Assunto
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