RESUMO
Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer, and ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of the biological and mechanistic rationale as to why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers. We first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Panc02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineering a Panc02 cell line that is suppressed for exosome biogenesis, implanting into the C56BL/6 mouse, and examining whether the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis results in the ablation of discriminatory salivary biomarker development. This study supports that tumor-derived exosomes provide a mechanism in the development of discriminatory biomarkers in saliva and distal systemic diseases.
Assuntos
Biomarcadores Tumorais/metabolismo , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/metabolismo , Saliva/metabolismo , Acetilcolina/metabolismo , Animais , Linhagem Celular Tumoral , Esterases/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Pâncreas/metabolismo , TranscriptomaRESUMO
PURPOSE: To determine factors conferring an increased risk of developing ocular hypertension secondary to the fluocinolone acetonide (FA) sustained-release surgical implant (Retisert). DESIGN: Retrospective, observational case series. METHODS: Patients with a history of chronic noninfectious posterior uveitis undergoing naïve surgical FA implantation from 2007 to 2018 at the University of Colorado were studied. Patient demographics and multiple clinical measures were noted one year before and after FA implantation. RESULTS: Twenty-nine eyes of 21 patients were studied. The median age experiencing an IOP rise vs median age experiencing no IOP rise post-FA implantation was 27.0 and 54.0 years old, respectively (p = .01). A pre-FA implant risk factor of needing future glaucoma surgery after FA implantation is prior to maximum IOP (p = .02). CONCLUSIONS: A risk factor of elevated post-FA implantation IOP includes younger age. A potential risk factor for glaucoma surgery after FA implantation was higher maximum IOP before FA implantation.
Assuntos
Fluocinolona Acetonida/efeitos adversos , Glucocorticoides/efeitos adversos , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/induzido quimicamente , Complicações Pós-Operatórias , Adolescente , Adulto , Idoso , Criança , Implantes de Medicamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Uveíte Posterior/tratamento farmacológicoRESUMO
We describe a rare case of an infant who was born with multiple congenital anomalies, including the absence of eyelids. This patient had many dysmorphic features consistent with a severe phenotype of ablepharon-macrostomia syndrome (AMS) including a fish-like appearance of the mouth, rudimentary ears, absence of body hair, thin skin, absent nipples, abdominal distension, and genital abnormalities. Upon presentation, there was severe exposure keratopathy causing large bilateral sterile ulcers culminating in corneal melting of both eyes. An amniotic membrane graft was used to attempt to maintain the corneal surface integrity. However, because of the late presentation, the corneas could not be salvaged. Extensive surgical reconstruction of both eyelids and bilateral penetrating keratoplasty was ultimately performed successfully to protect the ocular surfaces while trying to maximize the visual potential. Early amniotic membrane grafting may be done at the bedside and may help preserve the ocular in patients with severe eyelid deformities until more definitive treatment is performed.
RESUMO
The most commonly described indications for surgical management of closed depressed skull fractures are hematoma evacuation and repair of extensive cosmetic deformity. Venous sinus injury, which occurs in a subset of depressed skull fractures, is not typically listed as an indication for surgical treatment due to the potential for major venous hemorrhage associated with surgery near these structures. However, if patients exhibit signs and symptoms of intracranial hypertension and radiographic findings demonstrate sinus compromise, surgical elevation of the depressed skull fragments is indicated. The authors present the case of a 25-year-old woman with a depressed skull fracture secondary to a gunshot wound with symptomatic compromise in venous outflow of the posterior one-third of the superior sagittal sinus. The patient was treated with surgical decompression via bilateral craniectomy along with intracranial pressure-lowering medical therapy and had almost full resolution of her presenting symptoms with documented improvement in flow through the superior sagittal sinus. While the use of surgical treatment for these types of injuries is highly debated, the authors demonstrate here that safe, effective surgical management of these patients is possible and that surgical decompression should always be considered in the case of symptomatic venous sinus flow obstruction.
Assuntos
Cavidades Cranianas/lesões , Descompressão Cirúrgica/métodos , Craniectomia Descompressiva/métodos , Traumatismos Cranianos Penetrantes/cirurgia , Seio Sagital Superior/cirurgia , Ferimentos por Arma de Fogo/cirurgia , Adulto , Cavidades Cranianas/diagnóstico por imagem , Feminino , Traumatismos Cranianos Penetrantes/diagnóstico por imagem , Hemodinâmica/fisiologia , Humanos , Hipertensão Intracraniana/fisiopatologia , Hipertensão Intracraniana/cirurgia , Seio Sagital Superior/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Leiomyosarcoma is a malignant tumor of mesenchymal cells and is the most common soft-tissue sarcoma. Leiomyosarcoma is a notably rare tumor in the ophthalmic region and can be of primary, secondary or metastatic origin. To the best of our knowledge, there has only been one published case of leiomyosarcoma metastasis to the choroid. In this case study, we report two cases of primary leiomyosarcoma with metastasis to the choroid of the eye. Both cases displayed systemic metastasis and showed response to high dose plaque radiotherapy. Despite its prevalence as the leading form of sarcoma, leiomyosarcoma rarely metastasizes to the ocular region.
RESUMO
IMPORTANCE: Ocular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients. In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis. OBJECTIVE: To determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma. DESIGN, SETTING, AND PATIENTS: Retrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008. EXPOSURES: Enucleation, plaque radiotherapy, local resection, or thermotherapy. MAIN OUTCOMES AND MEASURES: Metastasis and death. RESULTS: Of 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%). The melanocytosis involved the sclera (92%), iris (17%), choroid (12%), eyelid (8%), and temporal fossa (1%). Eyes with melanoma and oculo(dermal) melanocytosis had a relative risk for metastasis 1.6 times greater compared with those with no melanocytosis (P < .001). Metastasis of uveal melanoma was 2.8 times higher in patients with iris melanocytosis (P < .001), 2.6 times higher with choroidal melanocytosis (P = .02), and 1.9 times higher with scleral melanocytosis (P < .001). By Kaplan-Meier estimates, metastasis in patients with oculo(dermal) melanocytosis vs no melanocytosis was 2% vs 1.8% at 1 year, 27% vs 15% at 5 years, and 48% vs 24% at 10 years (P < .001). By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009). CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis. All patients with oculo(dermal) melanocytosis should undergo ophthalmic examination and imaging on a twice-yearly basis because this could help with the early detection of melanoma.
Assuntos
Neoplasias Oculares/patologia , Melanoma/secundário , Nevo de Ota/patologia , Neoplasias Cutâneas/patologia , Neoplasias Uveais/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Transformação Celular Neoplásica/patologia , Criança , Pré-Escolar , Enucleação Ocular , Feminino , Humanos , Hipertermia Induzida , Masculino , Melanoma/mortalidade , Melanoma/terapia , Melanose/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Neoplasias Uveais/mortalidade , Neoplasias Uveais/terapia , Adulto JovemAssuntos
Amantadina/toxicidade , Antivirais/toxicidade , Edema da Córnea/induzido quimicamente , Endotélio Corneano/efeitos dos fármacos , Transtornos da Visão/induzido quimicamente , Edema da Córnea/diagnóstico , Edema da Córnea/fisiopatologia , Paquimetria Corneana , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos da Visão/diagnóstico , Transtornos da Visão/fisiopatologia , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologia , Suspensão de TratamentoAssuntos
Blefaroptose/diagnóstico , Distrofia Muscular Oculofaríngea/diagnóstico , Blefaroptose/genética , Blefaroptose/cirurgia , Éxons/genética , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular Oculofaríngea/genética , Distrofia Muscular Oculofaríngea/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Peptídeos/genética , Proteína I de Ligação a Poli(A)/genética , Repetições de TrinucleotídeosRESUMO
UNLABELLED: We report 2 cases of inadvertent filtering blebs that developed vision-threatening complications many years after uneventful cataract extraction with scleral incisions. These inadvertent blebs can create complications similar to the intentionally produced blebs from trabeculectomy surgery; thus, follow-up and management should be handled in a similar manner. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.
Assuntos
Extração de Catarata , Cirurgia Filtrante/efeitos adversos , Complicações Pós-Operatórias , Deiscência da Ferida Operatória/etiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/etiologia , Feminino , Humanos , Pressão Intraocular/fisiologia , Implante de Lente Intraocular , Edema Macular/etiologia , Infecções por Proteus/tratamento farmacológico , Infecções por Proteus/etiologia , Proteus mirabilis/isolamento & purificação , Esclerostomia , Deiscência da Ferida Operatória/microbiologia , Deiscência da Ferida Operatória/fisiopatologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologiaAssuntos
Síndrome do Nevo Basocelular/patologia , Neoplasias Palpebrais/patologia , Neoplasias do Seio Maxilar/patologia , Neoplasias Primárias Múltiplas , Neoplasias Cutâneas/patologia , Adulto , Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Síndrome do Nevo Basocelular/tratamento farmacológico , Neoplasias Palpebrais/tratamento farmacológico , Proteínas Hedgehog/antagonistas & inibidores , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias do Seio Maxilar/tratamento farmacológico , Piridinas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Tomografia Computadorizada por Raios XAssuntos
Braquiterapia/efeitos adversos , Neoplasias da Coroide/radioterapia , Radioisótopos do Iodo/efeitos adversos , Melanoma/radioterapia , Lesões por Radiação/patologia , Esclera/patologia , Idoso , Neoplasias da Coroide/diagnóstico por imagem , Neoplasias da Coroide/patologia , Feminino , Humanos , Melanoma/diagnóstico por imagem , Melanoma/patologia , Necrose , Observação , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Ultrassonografia , Acuidade VisualAssuntos
Doenças da Túnica Conjuntiva/diagnóstico , Infecções Oculares Bacterianas/diagnóstico , Granuloma/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Ocular/diagnóstico , Antituberculosos/uso terapêutico , Doenças da Túnica Conjuntiva/tratamento farmacológico , Doenças da Túnica Conjuntiva/microbiologia , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Granuloma/tratamento farmacológico , Granuloma/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/microbiologia , Radiografia Torácica , Teste Tuberculínico , Tuberculose Ocular/tratamento farmacológico , Tuberculose Ocular/microbiologiaRESUMO
OBJECTIVE: To determine the prevalence of hepatic abnormalities identified during abdominal computed tomography (CT) performed within 1 month of the diagnosis of primary uveal melanoma. METHODS: Retrospective review of CT reports generated within 1 month following diagnosis of uveal melanoma in 91 patients at Memorial Sloan-Kettering Cancer Center, New York, New York, from 2004 to 2009. RESULTS: Of 198 patients reviewed, 91 (46%) had a CT scan within 1 month of uveal melanoma diagnosis; 1 or more hepatic abnormalities were identified in 50 of these patients (55%). Abnormalities included 38 focal (13 solitary, 25 multiple) and 15 diffuse (11 partial, 4 complete) lesions. Six patients had hepatic lesions suspected to be metastatic melanoma, but this was confirmed in only 3. Lesions suspected to be metastases were more likely multiple than solitary (P = .03). Thirty-nine patients had other lesions, most commonly lesions that were too small to be characterized, a fatty liver, and hepatic cysts. Lesions in 5 of 50 patients with abnormalities could not be classified. Neither the protocol (triphasic vs nontriphasic) nor the center where the scan was performed (Sloan-Kettering vs other) was significantly related to the likelihood of identifying hepatic abnormalities in a given patient (P = .46 and P = .1, respectively). CONCLUSION: Although hepatic abnormalities were frequently identified in patients who underwent CT within 1 month of uveal melanoma diagnosis, metastatic disease was confirmed only in the setting of multiple lesions in only a minority of patients.