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BACKGROUND: The purpose was to describe the Nordic treatment practices and to reach a Nordic consensus for the treatment of sebaceous eyelid carcinoma. METHODS: The treatment practices data was collected by a questionnaire with 37 questions to the Nordic oculoplastic surgeons and analyzed. A PubMed MEDLINE database search was done to gather data on the published treatment practices and recommendations. A working group that consisted of in minimum one senior consultant from each leading Nordic University Eye Hospital was assigned. A structured interactive method was used to establish the consensus. RESULTS: Twenty-four doctors responded to the questionnaire. 23/24 (96%) of the respondents took a biopsy before surgery. Regional lymph node scanning was routinely done by 14/23 (61%) and a systemic screening of a metastatic disease by 13/23 (57%). 6/22 (27%) never took conjunctival mapping biopsies and 12/23 (52%) never screened for Muir- Torre. Respondents used Mohs surgery, frozen section or multi-stage excision with delayed closure, and 5-6 mm was the mostly preferred margin. Sentinel lymph node biopsy was a possible option for 9/22 (41%) and cryotherapy and Mitomycin C for 6/22 (27%) respondents. 50% of respondents considered radiation as a treatment option. 15/16 (94%) respondents always followed-up their patients, most for 5 years. Two thirds scanned regional lymph nodes during the follow-up. Consensus was reached for 18 statements representing three domains: preoperative work-up, treatment and follow-up. CONCLUSION: Treatment practices differ in between the five Nordic countries which have similar public health care systems. In the article the authors present a Nordic consensus for the treatment of eyelid sebaceous carcinoma.
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Adenocarcinoma Sebáceo/terapia , Consenso , Neoplasias de los Párpados/terapia , Párpados/patología , Neoplasias de las Glándulas Sebáceas/terapia , Adenocarcinoma Sebáceo/patología , Adulto , Anciano , Terapia Combinada/normas , Neoplasias de los Párpados/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Sebáceas/patología , Biopsia del Ganglio Linfático Centinela , Encuestas y CuestionariosRESUMEN
BACKGROUND: Ocular comorbidities are common in atopic dermatitis (AD) as the result of the disease itself or the use of medication. No large-scale epidemiologic data exist on the prevalence of ocular comorbidities in adults with AD. OBJECTIVES: We sought to examine the prevalence and risk of selected ocular comorbidities in adult patients with AD. METHODS: All Danish individuals ≥18 years of age were linked in nationwide registries. Adjusted hazard ratios (HRs) were estimated by means of Cox regression. RESULTS: A total of 5766 and 4272 adults were categorized as having mild and severe AD, respectively. At least 1 prescription of anti-inflammatory ocular agents was claimed in 12.0% and 18.9% of patients with mild and severe AD, respectively. In adjusted analysis, the HR of conjunctivitis was 1.48 (95% confidence interval [CI], 1.15-1.90) for mild AD and 1.95 (95% CI, 1.51-2.51) for severe AD. The HR of keratitis was 1.66 (95% CI, 1.15-2.40) for mild AD and 3.17 (95% CI, 2.31-4.35) for severe AD. For adults with severe AD, the HR for keratoconus was 10.01 (95% CI, 5.02-19.96). AD was associated with "cataract only" in individuals <50 years of age. LIMITATIONS: A limitation of the study is that observational studies cannot establish causality. CONCLUSIONS: Adults with AD had a significant and disease severity-dependent increased risk of development of conjunctivitis, keratitis, and keratoconus compared with that of the general population.
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Catarata/epidemiología , Conjuntivitis/epidemiología , Dermatitis Atópica/epidemiología , Queratitis/epidemiología , Queratocono/epidemiología , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Comorbilidad , Dinamarca/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Modelos de Riesgos Proporcionales , Sistema de Registros , Medición de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: To review and present the results of a one-step method employing a free tarsal plate graft and a myocutaneous pedicle flap plus a free skin graft for reconstruction of large upper eyelid defects after tumour surgery. METHODS: This was a retrospective case-series of 8 patients who underwent reconstruction of the upper eyelid after tumour removal. The horizontal defect involved 50-75% of the lid (3 pts.), more than 75% (3 pts.), and more than 75% plus the lateral canthus (2 pts.). The posterior lamella was reconstructed with contralateral upper eyelid tarsal plate. The anterior lamella was reconstructed with a laterally based myocutaneous pedicle flap in 7 patients, leaving a raw surface under the brow which was covered with a free skin graft. In 1 patient with little skin left under the brow, the anterior lamella was reconstructed with a bi-pedicle orbicularis muscle flap together with a free skin graft. RESULTS: All patients healed without necrosis, did not suffer from lagophthalmos, achieved reasonable cosmesis, and did not need lubricants. In one patient, a contact lens was necessary for three weeks because of corneal erosion. One patient still needs a contact lens 3 months after excision to avoid eye discomfort. CONCLUSION: Large upper eyelid defects can be reconstructed with a free tarsal plate graft and a laterally based myocutaneous pedicle flap in combination with a free skin graft. Two-step procedures can probably be avoided in most cases.
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Neoplasias de los Párpados/cirugía , Párpados/cirugía , Colgajo Miocutáneo , Procedimientos Quirúrgicos Oftalmológicos , Procedimientos de Cirugía Plástica/métodos , Trasplante de Piel , Anciano , Anciano de 80 o más Años , Músculos Faciales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculos Oculomotores/cirugía , Estudios RetrospectivosRESUMEN
PURPOSE: To investigate the functional and cosmetic results after primary surgical repair of bicanalicular lacerations. METHODS: We identified patients diagnosed with bicanalicular lacerations at the Eye Clinic of Rigshospitalet, Copenhagen from 2000 through 2009. Patient charts were reviewed and a telephone interview was conducted according to a standard questionnaire, regarding tearing and cosmesis. Symptoms (no epiphora, epiphora only when outdoors, epiphora when indoors, or epiphora with discharge) were compared to the healthy eye and scarring was graded from 0 to 10 by the patient (none to very disturbing). RESULTS: Fifteen patients had bicanalicular lacerations. Canalicular silicone stents were used in six different ways: two monostents to the lacrimal sac (n = 1), one monostent to the nose in the upper canaliculus (n = 2), two monostents to the nose (n = 2), bicanalicular stent to the nose (n = 7), bicanalicular anular stent (n = 2), bicanalicular stent and dacryocystorhinostomy (n = 1). The surgery was carried out by 6 different surgeons. Eleven patients could be followed up. In these, epiphora was reported after primary surgery by 7 patients, and scarring was graded to more than 1 in 4 patients. However, it is noteworthy that 3 of 4 patients operated with monostents had no symptoms; the fourth patient reported having epiphora indoors. Furthermore, the four patients operated with monostents graded their scaring to be 0 (n = 3) or 1 (n = 1) only. CONCLUSION: Sequelae are common after bicanalicular lacerations. The use of one or two monostents to the nose appears to be a reasonable alternative to the traditional use of one bicanalicular stent.
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Laceraciones/cirugía , Aparato Lagrimal/lesiones , Procedimientos Quirúrgicos Oftalmológicos , Dinamarca , Estética , Humanos , Complicaciones Posoperatorias , Stents , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of the present study was to investigate the correlation between Plexiform Neurofibroma (PN) of the eye region and Neurofibromatosis type 1 (NF1). According to the textbooks of ophthalmology, PN and NF1 are very closely linked. Our clinical experience raised doubts about this, however. METHODS: All biopsy reports from the Eye Pathology Institute, Copenhagen, for the 10-year period from 1999 to 2008 with PN as the histological diagnosis were identified. From the pathology referral forms, we determined whether the patients had had a history of NF1, and the medical records were reviewed for symptoms and signs of NF1. Patients with no known NF1 were invited for a clinical examination and a blood test for mutation analysis. RESULTS: 13 patients had been given the histological diagnosis of PN of the eye region during the 10-year period. Of these, 10 patients fulfilled the National Institute of Health (NIH) diagnostic criteria for NF1, but 3 patients had PN of the eye region as the only sign, and thus did not have NF1. In 2 of these patients, mutation analysis was performed on blood, and was negative. CONCLUSION: PN of the eye region is suggestive of NF1 but not pathognomonic of this disease.
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Neoplasias de los Párpados/diagnóstico , Neurofibroma Plexiforme/diagnóstico , Neurofibromatosis 1/diagnóstico , Neoplasias Orbitales/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Neoplasias de los Párpados/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurofibroma Plexiforme/cirugía , Neurofibromatosis 1/genética , Neurofibromina 1/genética , Neoplasias Orbitales/cirugía , Adulto JovenRESUMEN
An amelanotic, circum-corneal nevus in a 2-year-old child is described. The nevus presented at birth as a red spot in the nasal conjunctiva that subsequently enlarged to completely encircle the cornea. The tumour was partially removed three times, but at the age of 6 years, the nevus still covers the entire limbal region. The case illustrates that circum-corneal redness in a child may be caused by a nevus and that a conjunctival limbal nevus in a child tend to recur after incomplete excision.
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Neoplasias de la Conjuntiva/patología , Enfermedades de la Córnea/patología , Neoplasias del Ojo/patología , Recurrencia Local de Neoplasia/diagnóstico , Nevo/patología , Preescolar , Neoplasias de la Conjuntiva/cirugía , Enfermedades de la Córnea/cirugía , Neoplasias del Ojo/cirugía , Femenino , Estudios de Seguimiento , Humanos , Limbo de la Córnea/patología , Recurrencia Local de Neoplasia/cirugía , Nevo/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Agudeza VisualRESUMEN
BACKGROUND: Separately, cryotherapy and brachytherapy have shown promising results when adjuvating the excision of squamous cell carcinoma of the conjunctiva (SCCC). The aim of this paper is to assess the combined effect in terms of complications and recurrence rate. SUMMARY: We describe 2 patients suffering from SCCC, and we review the current literature on adjuvant cryotherapy and brachytherapy. Both patients, one of whom suffered from recurrent SCCC, underwent surgical excision followed by combined cryotherapy and brachytherapy. Cryotherapy was performed using a retinal cryoprobe, and 2 rounds each of 5 s with N2O as a cryogen were applied. Brachytherapy was performed using a ruthenium-106 plaque, delivering a dosage of 100 Gy at 2-mm depth. KEY MESSAGES: By reviewing the current literature and describing 2 case reports, this paper illustrates the use of combined cryotherapy and brachytherapy after surgical excision of SCCC. The current literature presents promising results of each treatment, and the 2 cases showed promising results by combining the 2 adjuvant therapies showing no signs of recurrence or complications during a follow-up period of 26 and 38 months.
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PURPOSE: Repair of large upper eyelid defects can be accomplished by both 1-stage and 2-stage techniques some of which are complicated and time consuming. I here present a simple 1-stage technique for upper eyelid reconstruction. METHODS: The records and the peroperative and postoperative photographs of two patients who underwent reconstruction of large full-thickness upper eyelid defects after tumor removal were reviewed. The posterior lamella was reconstructed with lip mucosa in one patient and with a hard palate graft in the other. The anterior lamella was reconstructed with a myocutaneous pedicle flap from the remaining upper eyelid with its base medially or laterally. The resulting skin defect under the eyebrow was covered by a free skin graft from the contra lateral upper eyelid. RESULTS: In both patients the flap healed without necrosis or any other complications. In the case where the posterior lamella was reconstructed with lip mucosa the cosmetic appearance was excellent, and the cornea remained unaffected throughout the postoperative period. In the case where a hard palate graft was used the cosmetic appearance was good, but the corneal epithelium developed an edema and a soft contact lens was needed. The visual acuity was 20/20 and 20/40, respectively, 3 months postoperatively. CONCLUSION: Large upper eyelid defects can successfully be reconstructed by a pedicle flap from the infra brow area, which subsequently is covered by a free skin graft.
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Enfermedades de los Párpados/cirugía , Membrana Mucosa/trasplante , Músculo Esquelético/trasplante , Procedimientos de Cirugía Plástica/métodos , Trasplante de Piel/métodos , Colgajos Quirúrgicos , Anciano , Femenino , Humanos , Persona de Mediana EdadRESUMEN
PURPOSE: To describe the prevalence of phantom eye syndrome in eye-amputated patients, to give a description of visual hallucinations, and to identify triggers, stoppers, and emotions related to visual hallucinations. METHODS: The hospital database was screened, using surgery codes for patients who had received ocular evisceration, enucleation, or secondary implantation of an orbital implant in the period 1993-2003. A total of 267 patients was found and invited to participate, 173 accepted. Patients who accepted participation had their records reviewed, and a structured interview about visual hallucinations and pain was performed by one trained questioner (M.L.R.R.). RESULTS: The prevalence of phantom eye syndrome was 51%. Elementary visual hallucinations were present in 36%, complex visual hallucinations in only 1%, and other visual hallucinations in 14%. The elementary visual hallucinations were most often white or colored light, as a continuous sharp light or as moving dots. The most frequent triggers were darkness, closing of the eyes, fatigue, and psychological stress; 54% of patients had the experience more than once a week. Ten patients were so visually disturbed that it interfered with their daily life. CONCLUSIONS: Phantom eye syndrome is common, and the authors recommend that surgeons inform their patients about the phenomenon.
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Enucleación del Ojo , Evisceración del Ojo , Alucinaciones/psicología , Trastornos de la Percepción/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Emociones/fisiología , Femenino , Alucinaciones/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Fenómenos Fisiológicos Oculares , Dolor/fisiopatología , Trastornos de la Percepción/fisiopatología , Prevalencia , Encuestas y Cuestionarios , Síndrome , Factores de Tiempo , Adulto JovenRESUMEN
Background/objectives: The intraorbital contents are thought to be affected by oedema in the days following a blowout fracture. We posit that this oedema can be detected by Magnetic resonance imaging (MRI) as changes in muscle volume, in muscle cross-sectional area, and in the MRI parameter 'mean grey value' (MGV) of the orbital fat and extraocular muscles (EOMs). Materials and methods: Patients with a blowout fracture underwent an MRI scan within 72 h after the trauma and again after 10-14 days. Measurements of EOMS and fat tissue on the fractured orbit were compared to the unfractured orbit. Results: Eighteen patients were included. Measurements showed significantly larger volume, cross-sectional area and MGV of the EOM closest to the fracture compared to the same muscle in the unfractured orbit. This significance disappeared for some parameters on the second scan. The volume of herniated orbital contents was significantly smaller on the second scan than on the first. Conclusions and significance: Based on the first longitudinal MRI study on patients with blowout fractures, our results indicate post-traumatic oedema in the intraorbital soft tissue which subsides between scans. A watchful waiting period is recommended in the initial post-traumatic days in patients without muscle entrapment.
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Edema/diagnóstico por imagen , Músculos Oculomotores/diagnóstico por imagen , Fracturas Orbitales/diagnóstico por imagen , Adolescente , Adulto , Anciano , Edema/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fracturas Orbitales/complicaciones , Adulto JovenRESUMEN
This study aimed to investigate the microRNA (miRNA) profile in primary tumors from conjunctival melanoma with and without subsequent metastatic spread along with their coupled distant metastases to identify miRNAs likely to be involved in metastatic progression. This observational study included 13 patients with metastatic conjunctival melanoma (follow-up: 1-39 years) treated at a Danish referral center. Twenty-five patients with nonmetastatic conjunctival melanoma (follow-up: 5-17 years) were included for comparison. Global miRNA profiling was performed with the Affymetrix GeneChip 4.1 microarray. Taqman qPCR arrays were used for validation. Significant differentially expressed miRNAs were defined as having a false discovery rate of less than 0.05. Primary conjunctival melanoma with and without subsequent metastatic spread clustered separately according to miRNA expression, and 15 miRNAs were found to have significant differential expression. Six miRNAs (hsa-miR-4528, hsa-miR-1270, hsa-miR-1290, hsa-mir-548f-4, hsa-mir-4278, and hsa-miR-34a-3p) were downregulated and nine miRNAs were upregulated (hsa-mir-575, hsa-miR-527, hsa-miR-518a-5p, hsa-miR-6759-5p, hsa-miR-8078, hsa-mir-4501, hsa-mir-622, hsa-mir-4698, and hsa-mir-4654) in primary conjunctival melanoma with subsequent metastatic spread. A comparison of primary conjunctival melanoma with their pair-matched metastases identified six significant differentially expressed miRNAs (hsa-miR-1246 and hsa-miR-302d-5p, hsa-mir-6084, hsa-miR-184, hsa-mir-658, and hsa-mir-4427). qPCR confirmed downregulation of hsa-miR-184 in the distant metastases when compared with the corresponding primary tumor. Primary conjunctival melanoma with and without subsequent metastatic spread separated clearly on the miRNA level when profiled with microarray-based methods. qPCR was able to replicate expression levels of one miRNA (hsa-miR-184) that was downregulated in metastases when compared with corresponding primary tumors.
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Neoplasias de la Conjuntiva/genética , Melanoma/genética , MicroARNs/genética , Anciano , Neoplasias Encefálicas/secundario , Neoplasias de la Conjuntiva/patología , Dinamarca , Progresión de la Enfermedad , Regulación hacia Abajo , Reacciones Falso Positivas , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias de la Parótida/secundario , Reacción en Cadena de la Polimerasa , Manejo de Especímenes , Neoplasias de la Glándula Submandibular/secundarioRESUMEN
PURPOSE: To evaluate the histological appearances of the epithelial cells and the clinical effect of the hard palate mucous membrane (HPM) graft for the treatment of lower eyelid retraction (LER). METHODS: This was a follow-up study involving 15 patients, with a total of 16 eyes operated. Five patients had LER as a result of Graves' ophthalmopathy and/or inferior rectus recession, six patients because of wearing an eye prosthesis, two patients because of previous tumour excision, one patient because of proptosis due to sphenoid wing meningioma and one patient because of previous lower eyelid blepharoplasty. Three imprint biopsies were taken from each patient, one from the tarsal conjunctiva in the healthy eye, one from the graft in the operated eye and one from unoperated hard palate. The inferior scleral show was measured on pre- and postoperative photographs and related to the horizontal corneal diameter. RESULTS: Median follow-up time was 21.2 [range 4.5-87.9] months. Imprints from the graft and the hard palate showed equally large epithelial cells; imprints from conjunctiva showed small epithelial cells. The mean (±SD) scleral show was 0.12 ± 0.09 cornea diameter before surgery and 0.0003 ± 0.08 cornea diameter at invited follow-up (p < 0.001, paired t-test). Corrected for direction of gaze, the mean improvement in scleral show was 0.12 ± 0.08 cornea diameter. Thirteen of 14 patients were satisfied with the final result. CONCLUSION: A HPM graft for LER maintains its native epithelial morphology and gives a lasting improvement in most patients.
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Blefaroplastia/métodos , Enfermedades de los Párpados/cirugía , Párpados/cirugía , Mucosa Bucal/trasplante , Paladar Duro/citología , Adulto , Anciano , Biopsia , Enfermedades de los Párpados/patología , Párpados/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mucosa Bucal/citología , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTION: Either a pass/fail approach or a seven-point grading scale are used to evaluate students at the Danish universities. The aim of this study was to explore any effect of the assessment methods on student performances during oral exams. METHODS: In a prospective study including 1,037 examinations in three medical subjects, we investigated the difference in the test scores between the spring- and autumn semester. In the spring semester, the students could either pass or fail the subject (pass/fail) while in the following autumn semester, the students were assessed by tiered grading (seven-point grading scale). Unknown to the students, the examiners assessed the students by the seven-point grading scale also in the spring semester. Students at the international classes who were officially assessed by the seven-point grading scale during both semesters served as control group. RESULTS: The grading scores were significantly higher among students who were aware of being evaluated with the seven-point grading scores compared with the pass/fail group (p < 0.0001). In comparison, no significant difference between the exam results was observed from the spring- to the autumn semester for the control group (p = 0.45). Moreover, the average mark was higher among the international students (mean = 10.3, on the seven-point grading scale) than in the Danish speaking classes (mean = 9.1). CONCLUSION: The seven-point grading scale seems to motivate students to yield a better performance; hence tiered-grading should probably be preferred to a simple pass/fail approach. FUNDING: none. TRIAL REGISTRATION: not relevant.
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Educación Médica/métodos , Evaluación Educacional/estadística & datos numéricos , Estudiantes de Medicina/psicología , Distribución de Chi-Cuadrado , Dinamarca , Dermatología/educación , Evaluación Educacional/métodos , Humanos , Oftalmología/educación , Otolaringología/educación , Estudios Prospectivos , Método Simple CiegoRESUMEN
PURPOSE: To investigate incidence, clinicopathological features and prognosis of BRAF-mutated conjunctival melanoma in Denmark. Furthermore, to determine BRAF mutations in paired premalignant lesions and evaluate immunohistochemical BRAF V600E oncoprotein detection. METHODS: Data from 139 patients with conjunctival melanoma (1960-2012) were collected. Archived conjunctival melanoma samples and premalignant lesions were analysed for BRAF mutations using droplet digital polymerase chain reaction (PCR). Results were associated with clinicopathological features and compared with BRAF V600E oncoprotein stainings. RESULTS: The overall incidence of conjunctival melanoma (0.5 cases/1 000 000/year) increased during the study period with 0.13 cases/1 000 000/10 years. The increase comprised a higher proportion of patients aged >65 years, epibulbar tumours and tumours developed from a primary acquired melanosis with atypia. BRAF mutations were identified in 39 of 111 (35%) cases. The rate ratio of BRAF-mutated versus BRAF-wild-type melanoma did not change over time. BRAF mutations were associated with T1 stage (p = 0.007), young age (p = 0.001), male gender (p = 0.02), sun-exposed location (p = 0.01), mixed/non-pigmented tumour colour (p = 0.02) and nevus origin (p = 0.005), but did not associate with prognosis. BRAF status in conjunctival melanoma and paired premalignant lesions corresponded in 19 of 20 cases. Immunohistochemistry detected BRAF V600E mutations with a sensitivity of 0.94 and a specificity of 1.00 in newer conjunctival melanoma samples (2000-2012, n = 47). CONCLUSION: The incidence of conjunctival melanoma increased in Denmark over 50 years. The proportion of BRAF-mutated conjunctival melanoma was constant. BRAF mutations were identified as early events in conjunctival melanoma, associated with a distinct clinicopathological profile, similar to BRAF-mutated cutaneous melanoma. Immunohistochemical detection of BRAF can be used to assess BRAF V600E mutations.
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Neoplasias de la Conjuntiva/epidemiología , Melanoma/epidemiología , Mutación , Lesiones Precancerosas/epidemiología , Proteínas Proto-Oncogénicas B-raf/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Conjuntiva/genética , Neoplasias de la Conjuntiva/patología , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Dinamarca/epidemiología , Femenino , Humanos , Incidencia , Masculino , Melanoma/genética , Melanoma/patología , Melanosis/epidemiología , Melanosis/genética , Melanosis/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Nevo Pigmentado/epidemiología , Nevo Pigmentado/genética , Nevo Pigmentado/patología , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Pronóstico , Adulto JovenRESUMEN
PURPOSE: Conjunctival melanoma (CM) is a rare disease associated with considerable mortality. As opposed to cutaneous melanoma, the epigenetic mechanisms involved in the development of CM and other mucosal melanomas (MMs) are unclear. The purpose of this study was to identify tumor-specific and prognostic microRNA (miRNA) in CM and to compare the miRNA profile with that of MM. METHODS: Using microarray analysis (Affymetrix) we determined the miRNA expression profile in 40 CMs compared with 7 normal conjunctival samples. Changes in miRNA expression were associated with T stage, local recurrence, metastasis, and mortality. Furthermore, the expression of six fresh frozen tissue samples of CM was compared with that of four laryngeal and sinonasal MM. RESULTS: Our analysis revealed 24 upregulated and 1 downregulated miRNA in CM; several of these miRNAs have key functions in the pathogenesis and progression of cutaneous melanoma. Additionally, we identified seven upregulated miRNAs specific for stage-T1 and stage-T2 CM, whose expression was associated with increased tumor thickness (P = 0.007), and two upregulated miRNAs (miR-3687 and miR-3916) associated with an increased risk of local recurrence. No stage T3-specific miRNAs were identified. CONCLUSIONS: We identified differentially expressed and potentially prognostic miRNAs in CM. Furthermore, the miRNA expression pattern of CM resembled that in MM. The identification of these differentially expressed miRNAs provides an entry point for future functional studies of miRNAs as prognostic or therapeutic targets in CM and highlights the resemblance between CM, MM, and cutaneous melanoma.
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Neoplasias de la Conjuntiva/genética , Regulación Neoplásica de la Expresión Génica , Melanoma/genética , MicroARNs/genética , ARN Neoplásico/genética , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Neoplasias de la Conjuntiva/metabolismo , Neoplasias de la Conjuntiva/patología , Humanos , Melanoma/metabolismo , Melanoma/patología , MicroARNs/biosíntesis , Persona de Mediana Edad , Pronóstico , Análisis por Matrices de Proteínas , Estudios RetrospectivosRESUMEN
IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter study was performed. Patient data were collected from January 1, 1980, through December 31, 2010. The dates of the analysis were May 15, 2015, to August 20, 2015. The median follow-up period was 43 months. Seven eye cancer centers were involved in the study. In total, 268 patients with CL were identified, 5 of whom were excluded because of missing clinical data. MAIN OUTCOMES AND MEASURES: Overall survival, disease-specific survival, and progression-free survival were the primary end points. RESULTS: Two hundred sixty-three patients with CL were included in the study. Their mean age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were frequently secondary diseases (41.7% [5 of 12] and 88.9% [16 of 18], respectively), with MCL showing a frequent occurrence of stage IVE lymphoma (61.1% [11 of 18]) and bilateral manifestation (77.8% [14 of 18]). Localized disease (stage IE or IIE) was commonly treated with external beam radiation therapy (EBRT) with or without chemotherapy, while widespread lymphoma (stage IIIE or IVE) and MCL of any stage were managed with chemotherapy with or without EBRT. Diffuse large B-cell lymphoma and MCL had a poor prognosis, with 5-year disease-specific survival of 55.0% and 9.0%, respectively, in contrast to EMZL (97.0%) and FL (82.0%). Further survival predictors included age (EMZL), sex (FL), and Ann Arbor staging classification (EMZL and FL). The American Joint Committee on Cancer TNM staging showed limited prognostic usefulness, only being able to predict survival for patients with DLBCL. CONCLUSIONS AND RELEVANCE: Conjunctival lymphoma consists of mainly 4 subtypes of B-cell non-Hodgkin lymphoma: EMZL, FL, MCL, and DLBCL. Mantle cell lymphoma is characterized by a particularly high frequency of secondary disease of stage IVE and bilateral manifestation. The histological subtype is the main outcome predictor, with MCL and DLBCL having a markedly poorer prognosis than EMZL and FL.
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Neoplasias de la Conjuntiva/epidemiología , Neoplasias de la Conjuntiva/patología , Linfoma/epidemiología , Linfoma/patología , Anciano , Biopsia con Aguja , Linfoma de Burkitt/epidemiología , Linfoma de Burkitt/patología , Linfoma de Burkitt/terapia , Neoplasias de la Conjuntiva/terapia , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Incidencia , Internacionalidad , Linfoma/terapia , Linfoma de Células B de la Zona Marginal/epidemiología , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/terapia , Linfoma Folicular/epidemiología , Linfoma Folicular/patología , Linfoma Folicular/terapia , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
IMPORTANCE: Large studies investigating clinical presentation and treatment in primary conjunctival melanoma (CM) are rare. Clinicopathological characteristics of BRAF-mutated CM have not been studied thoroughly. OBJECTIVES: To determine the associations of clinicopathological tumor features and treatment with local recurrence, metastasis, and mortality and to determine the association of BRAF mutations with these features. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study at the Eye Pathology Institute, Copenhagen, Denmark. Participants included 139 patients with primary CM in Denmark from January 1, 1960, to December 31, 2012. For BRAF analysis, all patients with available formalin-fixed, paraffin-embedded tumor samples from January 1, 1994, to December 31, 2012, were included. MAIN OUTCOMES AND MEASURES: BRAF mutations, local recurrence, regional and distant metastasis, melanoma-related mortality, and all-cause mortality were examined. RESULTS: A poor prognosis of tumors involving the extrabulbar conjunctiva and adjacent tissue structures was confirmed in multivariable Cox proportional hazards regression models. Patients undergoing incisional biopsy more frequently developed metastasis (hazard ratio [HR], 2.46; 95% CI, 1.08-5.58; P = .03). Excision without adjuvant treatment was associated with local recurrence (HR, 1.97; 95% CI, 0.11-3.48; P = .02), metastatic disease (HR, 2.51; 95% CI, 1.07-5.91; P = .03), and all-cause mortality (HR, 1.80; 95% CI, 1.05-3.08; P = .03). BRAF mutations were identified in 19 of 47 primary CMs (40.4%) and were more frequent in younger patients (P = .005), less frequent in the extrabulbar conjunctiva (P = .05), more frequently classified as T1 tumors (P = .03), and rarely manifested with primary acquired melanosis (P = .001) or with a uniformly pigmented lesion (P = .006). Distant metastases developed in 6 of 19 BRAF-mutated CMs (31.6%) as opposed to 1 of 28 BRAF wild-type CMs (3.6%). No definitive association with distant metastasis was seen in multivariable Cox proportional hazards regression models. CONCLUSIONS AND RELEVANCE: Incisional biopsy and excision without adjuvant therapy were associated with a poor outcome in patients with CM. Extrabulbar location was also associated with a poor outcome in multivariable analysis. BRAF-mutated CMs were frequent in younger patients and were rare in tumors involving the extrabulbar conjunctiva. Despite a more favorable location, BRAF-mutated tumors may be associated with more frequent distant metastasis.
Asunto(s)
Neoplasias de la Conjuntiva , Melanoma , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Neoplasias de la Conjuntiva/diagnóstico , Neoplasias de la Conjuntiva/genética , Neoplasias de la Conjuntiva/mortalidad , Neoplasias de la Conjuntiva/terapia , Análisis Mutacional de ADN , Dinamarca/epidemiología , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/diagnóstico , Melanoma/genética , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Reacción en Cadena de la Polimerasa , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
PURPOSE: To characterize the clinicopathological features of diffuse large B-cell lymphoma (DLBCL) of the ocular adnexal region. METHODS: The present series of orbital and adnexal DLBCLs were found by searching the Danish Registry of Pathology between 1980 and 2009. Histological specimens were re-evaluated using a panel of monoclonal antibodies. Clinical files from all patients with confirmed DLBCL were collected. RESULTS: A total of 34 patients with DLBCL of the ocular adnexal region were identified. Eighteen of the patients were men. The patients had a median age of 78 years (range 35-97 years). Ninety-seven per cent of the patients had unilateral ocular adnexal region involvement, and the orbit (76%) was the most frequently affected site. Nineteen patients (56%) presented with Stage I lymphoma. Of these, 18 were diagnosed with primary lymphoma. Four patients (12%) had Stage II, one patient (3%) had Stage III and ten patients (29%) presented with Stage IV lymphoma. The 5-year overall survival (OS) rate for the whole study group was 20%. The patients with Stage I lymphoma had a significantly better 5-year OS rate (28%) than patients in Stage II-IV (5-year OS rate, 9%). In Cox regression analysis, concordant bone marrow involvement and the International Prognostic Index (IPI) score were prognostic factors for OS. CONCLUSIONS: Diffuse large B-cell lymphoma of the ocular adnexal region is mainly prevalent in elderly patients. Most patients had unilateral orbital involvement. The overall prognosis is poor. Concordant bone marrow involvement and the IPI score were independent prognostic factors for mortality.
Asunto(s)
Neoplasias de la Conjuntiva/patología , Neoplasias de los Párpados/patología , Enfermedades del Aparato Lagrimal/patología , Linfoma de Células B Grandes Difuso/patología , Neoplasias Orbitales/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Neoplasias de la Conjuntiva/química , Neoplasias de la Conjuntiva/terapia , Neoplasias del Ojo/química , Neoplasias del Ojo/patología , Neoplasias del Ojo/terapia , Neoplasias de los Párpados/química , Neoplasias de los Párpados/terapia , Femenino , Humanos , Enfermedades del Aparato Lagrimal/terapia , Linfoma de Células B Grandes Difuso/química , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orbitales/química , Neoplasias Orbitales/terapia , Sistema de Registros , Tasa de SupervivenciaRESUMEN
PURPOSE: The developing visual cortex has a strong potential to undergo plastic changes. Little is known about the potential of the ageing visual cortex to express plasticity. A pertinent question is whether therapeutic interventions can trigger plastic changes in the ageing visual cortex by restoring vision. METHODS: Twelve patients aged 50-85 years underwent structural high-resolution T1-weighted MRI of the whole brain 2 days and 6 weeks after unilateral cataract surgery. Voxel-based morphometry (VBM) based on T1-weighted magnetic resonance imaging (MRI) was employed to test whether cataract surgery induces a regional increase in grey matter in areas V1 and V2 of the visual cortex. RESULTS: In all patients, cataract surgery immediately improved visual acuity, contrast sensitivity and mean sensitivity in the visual field of the operated eye. The improvement in vision was stable throughout the 6 weeks after operation. VBM revealed a regional expansion of grey matter volume in area V2 contralateral to the operated eye during the 6-week period after surgery. Individual increases in grey matter were predicted by the symmetry in visual acuity between the operated eye and nonoperated eye. The more symmetrical visual acuity became after unilateral cataract surgery, the more pronounced was the grey matter increase in visual cortex. CONCLUSION: The data suggest that cataract surgery triggered a use-dependent structural plasticity in V2 presumably through improved binocular integration of visual input from both eyes. We conclude that activity-dependent cortical plasticity is preserved in the ageing visual cortex and may be triggered by restoring impaired vision.