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INTRODUCTION: Moyamoya syndrome associated with Williams syndrome is very rare but has been reported to have severe outcomes. Here, we reported a case of Williams syndrome with moyamoya syndrome that was confirmed by the presence of an RNF213 mutation. CASE PRESENTATION: A 6-year-old boy with Williams syndrome presented with right hemiparesis induced by hyperventilation. Magnetic resonance angiography and cerebral angiography showed severe stenosis of the bilateral internal carotid arteries and development of moyamoya vessels. Genetic analysis identified a heterozygous c.14576G>A (p.R4859K) mutation in RNF213. Moyamoya syndrome was diagnosed, and bilateral indirect revascularization surgery was conducted without complications and with a good postoperative course. In moyamoya syndrome associated with Williams syndrome, adequate perioperative management of both the moyamoya arteries and the cardiovascular abnormalities is important to prevent complications. CONCLUSION: This was the first report on a case in which moyamoya syndrome associated with Williams syndrome was confirmed by the presence of a heterozygous RNF213 mutation. Similar to the workup of moyamoya disease, confirmation of RNF213 mutation in Williams syndrome may be useful in predicting the development of moyamoya syndrome that can lead to severe complications.
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Doença de Moyamoya , Síndrome de Williams , Masculino , Humanos , Criança , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/genética , Predisposição Genética para Doença , Síndrome de Williams/complicações , Síndrome de Williams/diagnóstico por imagem , Síndrome de Williams/genética , Adenosina Trifosfatases/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
The purpose of treatment for unilocular intracranial cysts (UICs) is to release elevated intracranial pressure. Neuroendoscopic fenestration (NF) is one of the most effective and minimally invasive options for treating UICs, especially in young children; however, the optimal location and number of fenestrations, the necessity of using endoscopic third ventriculostomy (ETV) in combination with fenestration, and the course of treatment are not well known. We retrospectively reviewed the hospital records between 2012 and 2019. The patients were studied in terms of sex, age at surgery, preoperative symptoms, cyst localization and size, course of treatment, ventricular diameter, developmental assessment, anatomical location, and the number of fenestrations. There were four eligible patients in the relevant period: two boys and two girls. The median age at the time of surgery was 16 months. With regard to the location of the cysts, there were two cases of cavum velum interpositum (CVI), one case of quadrigeminal cistern, and one case of an isolated lateral ventricle. The most common preoperative finding was an enlarged head circumference. All the patients were treated with NF, including one case of reoperation after open head surgery. Postoperatively, we used the frontal and occipital horn ratio (FOHR) to evaluate the ventricular size. The average reduction in the FOHR was 0.003. In the most recent developmental assessment or examination during the follow-up period, two patients showed normal development, and two patients showed developmental delay. Based on our past experience and reports, we believe that it is recommended to perform two fenestrations for a single cyst. This is because it creates a flow of cerebrospinal fluid (CSF) within the cyst into normal CSF reflux. For lesions with obstruction of the aqueduct, such as cysts in the quadrigeminal cistern, ETV should be considered if it can be performed safely, in preparation for the worsening of hydrocephalus due to obstruction by enlargement of the cyst.
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Cistos , Hidrocefalia , Neuroendoscopia , Criança , Pré-Escolar , Cistos/cirurgia , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Ventrículos Laterais/patologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , VentriculostomiaRESUMO
Amniotic band syndrome (ABS) is a congenital abnormality that can cause a variety of deformities. Here, we report a case of ABS in which the amniotic band adhered to the skull, causing a partial cranial defect that was difficult to differentiate from an occipital encephalocele. The mother was a 24-year-old with an unremarkable medical and family history. Ultrasonography performed at 16 weeks showed that the fetus had a membranous structure in the occipital region. Occipital encephalocele was suspected, and she underwent cesarean section at 38 weeks. A male newborn was delivered, and his left occipital skin had a defect measuring 2 cm, from which a cystic structure had prolapsed. Cranial magnetic resonance imaging showed that the cystic structure had homogeneous high signal intensity on T2-weighted images. The neonate then underwent repair of the occipital encephalocele. During the operation, the membranous structures and dura were not continuous. Histological examination revealed that the membranous structures were composed of amnion, suggesting that this was a case of ABS. ABS may present with an encephalocele-like morphology without affecting the brain tissue and meninges. If an atypical encephalocele is found after birth, examination of the placenta may be helpful for a definitive diagnosis.
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Síndrome de Bandas Amnióticas , Encefalocele , Síndrome de Bandas Amnióticas/complicações , Síndrome de Bandas Amnióticas/diagnóstico por imagem , Síndrome de Bandas Amnióticas/cirurgia , Cesárea/efeitos adversos , Encefalocele/complicações , Encefalocele/diagnóstico por imagem , Encefalocele/cirurgia , Feminino , Humanos , Recém-Nascido , Masculino , Fenótipo , Gravidez , Crânio/patologiaRESUMO
BACKGROUND: Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor, with radiation therapy (RT) the only intervention that transiently delays tumor progression. Hypofractionated RT and re-irradiation at first progression have gained popularity in improving the quality of life of such patients. METHODS: We performed a retrospective review of children with DIPG treated at Kanagawa Children's Medical Center from 2000 to 2018. RESULTS: A total of 24 cases were reviewed. Median age at diagnosis was 6.3 years (1.6-14.0). Twenty patients received RT only once. Thirteen patients received conventionally fractionated RT, and seven patients received hypofractionated RT as up-front RT. Severe toxicities were not observed in patients who received hypofractionated RT. Median OS and time to progression were similar between conventionally fractionated and hypofractionated RT groups.(9.7 [95% confidence interval(CI): 7.1-11.2] versus 11.0[95% CI: 5.2-13.6] months, P = 0.60; 4.2[95% CI: 1.8-8.3] versus 7.1 [95% CI:4.5-8.7] months, P = 0.38). Four patients received re-irradiation at first progression and all patients showed transient neurological improvement and survival more than a year after diagnosis. A 4-year-old boy was re-irradiated 5-and-a-half months after the first re-irradiation; following transient neurological improvement. He survived a further 5 months. CONCLUSION: Hypofractionated RT for children with newly diagnosed DIPG is well tolerated and feasible from the viewpoint of reducing a patient's burden of treatment. Re-irradiation at first progression is suggested to be beneficial.
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Neoplasias do Tronco Encefálico/radioterapia , Glioma Pontino Intrínseco Difuso/radioterapia , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , Qualidade de Vida , Reirradiação , Estudos RetrospectivosRESUMO
STUDY DESIGN: Cohort study. OBJECTIVES: Long-term urological outcomes in patients with spinal lipoma after prophylactic tethered cord release (TCR) in infancy were investigated. SETTING: Children's hospital in Yokohama, Japan. METHODS: Children under one year of age with spinal lipoma who underwent TCR between 1990 and 2010 were investigated. According to Arai's classification, lipomas other than filar lipoma were classified into four types: caudal, dorsal, transitional, and lipomyelomeningocele. The level of the conus medullaris was divided into three categories: L3-5, L5/S1, and sacral. Urological outcomes, including the need for clean intermittent catheterization (CIC), urinary incontinence, presence of renal deterioration, and the need for bladder augmentation, were investigated by both lipoma type and level of the conus medullaris. RESULTS: Fifty-three patients met the inclusion criteria. The median follow-up period was 14.2 years (interquartile range 9.6-17.6 years). Of the 53 patients, ten (19%) were on CIC, and six (11%) were incontinent. Overall, two patients (4%) had renal deterioration detected by DMSA renal scan, and two (4%) needed augmentation cystoplasty. Of the lipoma types, transitional type showed the worst outcomes with respect to need for CIC (54%) and urinary incontinence (38%). There were no significant differences in renal deterioration and the rate of bladder augmentation by lipoma type. No urological outcomes were significantly associated with conus level. CONCLUSIONS: Even after prophylactic TCR in infancy in children with spinal lipoma, 19% of patients needed CIC in long-term follow-up. Of the lipoma types, transitional type showed the worst outcomes with respect to need for CIC and urinary incontinence.
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Cateterismo Uretral Intermitente , Lipoma/complicações , Procedimentos Neurocirúrgicos , Neoplasias da Medula Espinal/complicações , Doenças Urológicas/etiologia , Adolescente , Criança , Feminino , Seguimentos , Humanos , Lactente , Lipoma/cirurgia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Neoplasias da Medula Espinal/cirurgia , Doenças Urológicas/terapiaRESUMO
PURPOSE: The purpose of this study was to evaluate the incidence of peri-implantitis and to identify potential associated risk indicators. METHODS: This longitudinal study included 477 patients treated with 1420 implants. Medical and dental histories were evaluated in all patients. The location, size, connection type, surgical protocol, use of prosthesis splinting and fixation type were evaluated for each implant. In peri-implant evaluation, minimum keratinized tissue width around implants, peri-implant probing depths, peri-implant bleeding and peri-implant suppuration were assessed. Bone resorption around implants was evaluated with intraoral radiographs at baseline and at follow-up examinations. The study endpoint was peri-implantitis, which was defined as the presence of bleeding on probing and/or suppuration with bone resorption >1mm, in accordance with previous studies. Data were analyzed with mixed-effects Cox models. RESULTS: Peri-implantitis occurred in 15.3% of patients and 9.2% of implants. The overall 5- and 10-year cumulative implant survival rates were 0.95 (95% confidence interval [CI]: 0.93-0.96) and 0.83 (95% CI: 0.8-0.87), respectively. Age (hazard ratio [HR]=0.94, 95% CI: 0.90-0.98, p<0.01), plaque control record >20% (HR=2.61, 95% CI: 1.02-6.67, p=0.04), maxillary placement (HR=1.90, 95% CI: 1.11-3.23, p=0.02) and number of occlusal supports (HR=0.87, 95% CI: 0.77-0.99, p=0.03) were significantly correlated with peri-implantitis development. CONCLUSIONS: Within the limitations of this longitudinal study on risk indicators for peri-implantitis, age, inadequate plaque control, insertion in the maxilla and less occlusal support of natural teeth correlated with peri-implantitis development.
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Implantes Dentários/efeitos adversos , Peri-Implantite/etiologia , Falha de Prótese , Fatores Etários , Idoso , Perda do Osso Alveolar , Placa Dentária/prevenção & controle , Prótese Dentária/efeitos adversos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Peri-Implantite/epidemiologia , Medição de Risco/métodos , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: The presence/absence of postoperative anemia are presumed to have an impact on early recovery after surgery. This study was performed to compare hip muscle strength and hemoglobin during the perioperative period in 82 patients undergoing THA. METHODS: Evaluation of presence/absence of anemia was performed by calculating the 10-day postoperative/preoperative Hb ratio. Muscle strength was investigated before and 2 months after surgery. RESULTS: Postoperative SLR strength showed a significant difference between the patients whose 10-day postoperative/preoperative Hb ratio was <85% and ⧠85%. CONCLUSION: We need to consider perioperative strategies to minimize anemia in order to improve patient outcomes.
RESUMO
BACKGROUND: We think that it is necessary to evaluate whether the patient after total hip arthroplasty has achieved age-appropriate locomotor ability by improvement in hip joint function. The 25-question Geriatric Locomotive Function Scale (GLFS-25) have been determined age-specific standard values for the general population. The aim of this study was to compare postoperative hip muscle strength and functional performance at 3 months after THA with preoperative levels, and to compare the outcomes at 3 months after THA with the function of age-matched adults without hip disease. METHODS: The GLFS-25 scores and muscle strength were investigated before THA and 3 months after surgery in 12 men and 75 women who underwent total hip arthroplasty. RESULTS: The mean preoperative and postoperative GLFS-25 score was 55.4 and 19.1, respectively. With regard to the influence of age, the mean scores before and after THA were respectively 52.0 versus 18.2 for patients aged 60-69 years and 61.2 versus 17.3 for those aged 70-79 years in the normal/mild OA group. When female patients from the normal/mild OA group and the implant group classified into levels 4-7 after THA were combined (n = 15), their mean preoperative and postoperative straight leg raising (SLR) strength was 0.56 Nm/kg and 0.75 Nm/kg, respectively. On the other hand, the mean preoperative and postoperative SLR strength was respectively 0.54 Nm/kg and 0.86 Nm/kg for patients classified into levels 1-3 after THA (n = 45). CONCLUSION: Before THA, 90% of the patients who has severe hip disturbance were in need of nursing care (levels 4-7), while the percentage decreased to 30% after surgery. There was a difference of SLR muscle strength between the patients in levels 4-7 and those in levels 1-3 after THA, suggesting that achieving levels 1-3 postoperatively might depend on whether SLR muscle strength shows improvement.
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Artroplastia de Quadril , Locomoção/fisiologia , Força Muscular/fisiologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Quadril/cirurgia , Recuperação de Função Fisiológica/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
A 46-year-old diabetic man underwent the removal of a hematoma caused by traumatic brain injury. After surgery, severe hyponatremia occurred. The subsequent administration of NaCl and fludrocortisone improved his laboratory findings. The patient was transferred to our hospital, and his insulin therapy was replaced by teneligliptin. One week later, ipragliflozin treatment was initiated and induced an immediate increase in the serum sodium levels. NaCl and fludrocortisone were therefore discontinued. However, hyponatremia recurred after ipragliflozin withdrawal due to a urinary tract infection. NaCl and fludrocortisone were initiated again, and the laboratory data improved. We herein report a case of serum sodium fluctuation related to ipragliflozin administration.
Assuntos
Lesões Encefálicas Traumáticas/complicações , Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/complicações , Glucosídeos/efeitos adversos , Sódio/sangue , Tiofenos/efeitos adversos , Fludrocortisona/uso terapêutico , Glucosídeos/uso terapêutico , Humanos , Hiponatremia/tratamento farmacológico , Hiponatremia/etiologia , Insulina , Masculino , Pessoa de Meia-Idade , Sódio/metabolismo , Tiofenos/uso terapêuticoRESUMO
We encountered three patients with dysuria who had undergone spinal surgery for spina bifida during infancy. The patients presented with mental disability and dysbasia. Difficulty in urination, urinary incontinence, and a residual sensation of urine were resolved through intermittent self-catheterization in all patients. It was speculated that treatment for dysuria in these patients was delayed because they were not aware of its association with their condition during infancy, dysuria was relatively mild, and they had no history of febrile urinary tract infection. It is important for attending physicians to explain to parents of such infants the possible association of spina bifida with the future risk of dysuria, and to consider long-term follow-up to monitor their outcome.
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Disuria/etiologia , Disrafismo Espinal/cirurgia , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Disrafismo Espinal/complicaçõesRESUMO
OBJECTIVE: To clarify the healing-promoting effects of carbon dioxide laser irradiation in high and low reactive-level laser therapies (HLLT and LLLT, respectively) on extraction sockets after tooth extraction. MATERIAL AND METHODS: Forty-two 5-week-old male Wistar rats were divided into laser irradiation and non-irradiation (control) groups and compared. The laser-irradiation group underwent HLLT immediately after tooth extraction and then LLLT 1 day post-extraction. Tissue was excised 6 h and 3, 7, or 21 days after extraction and histopathologically investigated. The alveolar crest height was measured osteomorphometrically 21 days post-extraction, and granulation tissue in the extraction socket surface layer was immunohistologically investigated using anti-α-smooth muscle actin (anti-α-SMA) antibody 3 and 7 days post-extraction. RESULTS: Many osteoclasts appeared and active bone resorption was noted in the irradiation group 3 days after extraction compared to the controls. On Day 7, new bone formation started around the extraction socket in the control group, but from the superficial to over the middle layer of the socket in the irradiation group. On Day 21, a concavity existed in the alveolar crest region in the controls, whereas this region was flat, with no concavity, in the irradiation group. On osteomorphometry, the alveolar crest height was significantly higher in the irradiation (0.7791 ± 0.0122) than the control (0.6516 ± 0.0181) group (P < 0.05). On immunostaining, many α-SMA-positive cells were noted in the control group, but very few in the irradiation group. CONCLUSION: Laser-irradiated extraction wound healing showed characteristics different from those of the normal healing process, suggesting a favorable healing-promoting effect.
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Remodelação Óssea/efeitos da radiação , Lasers de Gás/uso terapêutico , Terapia com Luz de Baixa Intensidade , Miofibroblastos/fisiologia , Alvéolo Dental/efeitos da radiação , Cicatrização/efeitos da radiação , Actinas/análise , Animais , Dióxido de Carbono , Tecido de Granulação , Masculino , Osteoclastos/fisiologia , Doses de Radiação , Ratos , Ratos Wistar , Extração DentáriaRESUMO
Three neonates presented with split cord malformation (SCM) associated with myelomeningocele (MMC), complicated with various coexisting anomalies. All patients were female and classified as SCM type I. All patients had a syrinx located rostral to the SCM. One patient had hydrocephalus and Chiari malformation causing serious respiratory problems. Two patients had partial hypertrichosis located close to the MMC, suggesting association with SCM. One patient had sacral hypoplasty and right kidney agenesis, suggesting that some embryologic errors may affect not only neural but also mesodermal development. All patients underwent surgical treatment for SCM after detailed evaluation and management of concomitant anomalies, and developed no new neurological deficits. Delayed surgery is an alternative treatment strategy for SCM in patients with both SCM and MMC with similar complications.
Assuntos
Meningomielocele/complicações , Medula Espinal/anormalidades , Disrafismo Espinal/complicações , Siringomielia/complicações , Criança , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Vértebras Lombares/anormalidades , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Meningomielocele/diagnóstico por imagem , Meningomielocele/cirurgia , Radiografia , Medula Espinal/diagnóstico por imagem , Disrafismo Espinal/classificação , Disrafismo Espinal/diagnóstico por imagem , Disrafismo Espinal/cirurgia , Siringomielia/diagnóstico por imagem , Siringomielia/cirurgia , Resultado do TratamentoRESUMO
A case of skin injuries due to stings by crown-of-thorns starfish, Acanthaster planci, in a 53-year-old Okinawan woman is reported. She went to a beach to gather shellfish on 8 April 2001 and fell to the ground with her left palm on a crown-of-thorns starfish that happened to be close to her. She hurried to the emergency section of our hospital. An emergency doctor sterilized the wound and administered an antibiotic, an analgesic agent and an injection of a tetanus antitoxin. He tried to remove the remaining spines from the palm with great difficulty. Because swelling and subcutaneous indurations of the left palm had persisted thereafter, oral and topical administration of corticosteroid started on 13 April. Physical examination at the dermatology section revealed approximately 10 stab wounds of the left palm with pus, subcutaneous bleeding and many abrasions around them. X-rays of the left hand showed foreign bodies, 2-10 mm in size, located on the lesions. The patient was treated with a topical injection of 2 mg triamcinolone acetonide (Kenacort-A), diluted fivefold with 1% Xylocaine, once a week. Some of the foreign body granulomatous lesions improved but pain and subcutaneous indurations persisted in most of the lesions. Because the X-ray photographs showed many remaining spines, surgical excision to remove them was performed under local anesthesia 3 months after the injury. All the symptoms improved after the operation. Scanning electron microscopic examination of the spines revealed that their tips had fragile lattice-like structures.
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Mordeduras e Picadas/terapia , Corpos Estranhos/etiologia , Corpos Estranhos/terapia , Pele , Estrelas-do-Mar , Animais , Feminino , Corpos Estranhos/diagnóstico , Humanos , Pessoa de Meia-IdadeRESUMO
A 59-year-old woman with autoimmune hepatitis was referred to our hospital for examination of a liver tumor detected in 2001. A CT scan showed a hypovascular mass, and a liver biopsy revealed the presence of an inflammatory pseudotumor. A June 2003 CT scan showed enlargement of the tumor and polycystic pathological changes. Echinococcus antibody was positive, and a diagnosis of liver hydatid disease was made. A liver left lobe resection was performed. CT was useful in this case for detecting change in the lesion and for making the diagnosis of liver hydatid disease.
Assuntos
Equinococose Hepática/diagnóstico por imagem , Fígado/patologia , Tomografia Computadorizada por Raios X , Progressão da Doença , Equinococose Hepática/patologia , Feminino , Hepatite Autoimune/complicações , Humanos , Pessoa de Meia-IdadeRESUMO
Activation of Wnt signaling has been implicated in tumorigenesis, and epigenetic silencing of Wnt antagonist genes has been detected in various cancers. In the present study, we examined the expression and methylation of DICKKOPF (DKK) family genes in gastrointestinal cancer cell lines. We found that all known DKK genes were frequently silenced in colorectal cancer (CRC) cells (DKK1, 3/9, 33%; DKK2, 8/9, 89%; DKK3, 5/9, 56% and DKK4, 5/9, 56%), but not in normal colon mucosa. DKK1, -2 and -3 have 5' CpG islands, and show an inverse relation between expression and methylation. DKK methylation also was frequently observed in gastric cancer (GC) cell lines (DKK1, 6/16, 38%; DKK2, 15/16, 94% and DKK3, 10/16, 63%), but was seen less frequently in hepatocellular carcinoma and pancreatic cancer cell lines. DKKs also were frequently methylated in primary CRCs (DKK1, 7/58, 12%; DKK2, 45/58, 78% and DKK3, 12/58, 21%) and GCs (DKK1, 15/31, 48%; DKK2, 26/31, 84% and DKK3, 12/31, 39%). Against a background of CTNNB1 or APC mutations, Dickkopfs (Dkks) were less effective inhibitors of Wnt signaling than secreted frizzled-related proteins, though over-expression of Dkks suppressed colony formation of CRC cells with such mutations. Our results demonstrate that DKKs are frequent targets of epigenetic silencing in gastrointestinal tumors, and that loss of DKKs may facilitate tumorigenesis through beta-catenin/T-cell factor-independent mechanisms.
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Neoplasias Gastrointestinais/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Linhagem Celular Tumoral , Proliferação de Células , Quimiocinas , Metilação de DNA , Epigênese Genética , Neoplasias Gastrointestinais/patologia , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Regiões Promotoras Genéticas , Transdução de Sinais , Proteínas Wnt/metabolismoRESUMO
We present 2 patients with synchronous Ewing sarcoma family of tumors (ESFTs) and fibro-osseous lesion in the independent sites, possibly causing misjudgment in staging. Each patient showed another activity apart from the primary ESFT lesion on gallium and/or thallium scintigraphy at initial presentation. Of note is that such lesions showed no obvious radiologic change even though the primary ESFT lesions were mildly shrunken during chemotherapy. The biopsies confirmed fibrous dysplasia (FD) in the first patient and fibro-osseous lesion, possibly FD in the second patient. As far as we know, concurrent ESFT and FD in independent sites have never been described. However, this unusual combination emphasized the possibility of concurrent FD mimicking metastasis in a patient with malignancy and the view that exploratory biopsy should be performed in a critical case to make staging. Further investigation will be required about whether the co-occurrence of ESFD and FD in our patients is coincidence or genetic linkage.
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Neoplasias Ósseas/patologia , Fibroma Ossificante/patologia , Displasia Fibrosa Óssea/patologia , Sarcoma de Ewing/patologia , Adolescente , Biópsia , Criança , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Masculino , Metástase Neoplásica , Estadiamento de NeoplasiasRESUMO
Weight gain is a common sequela of suprasellar tumors, referred to as hypothalamic obesity. We undertook an evaluation of obesity and metabolic aberrations among patients treated at our institute. During the 12 mo from Apr. 2005, 23 patients (10 males and 13 females) with remitted suprasellar tumors attended our clinic: 10 patients with craniopharyngioma, 7 with germinoma, 4 with optic nerve glioma and others. Of these, 12 patients (52%) were found to have obesity on the basis of percent overweight and/or percent body fat. Elevated cholesterol and/or triglyceride (TG) was found in 9 patients (39%), and insulin resistance was suspected in 7 patients (30%). Three patients exhibited strikingly elevated postprandial TG levels. All 6 patients with the growth without GH phenomenon had at least one metabolic aberration. In conclusion, the prevalence of hypothalamic obesity was nearly half in our series, and hyperlipemia and insulin resistance were also frequently found. The increased risk for metabolic aberration in growth without GH patients was suggested.
RESUMO
Evidence now suggests that epigenetic abnormalities, particularly altered DNA methylation, play a crucial role in the development and progression of human gastrointestinal malignancies. Two distinct DNA methylation abnormalities are observed together in cancer. One is an overall genome-wide reduction in DNA methylation (global hypomethylation) and the other is regional hypermethylation within the CpG islands of specific gene promoters. Global hypomethylation is believed to induce proto-oncogene activation and chromosomal instability, whereas regional hypermethylation is strongly associated with transcriptional silencing of tumor suppressor genes. To date, genes involved in regulation of the cell cycle, DNA repair, growth signaling, angiogenesis, and apoptosis, are all known to be inactivated by hypermethylation. Recently developed techniques for detecting changes in DNA methylation have dramatically enhanced our understanding of the patterns of methylation that occur as cancers progress. One of the key contributors to aberrant methylation is aging, but other patterns of methylation are cancer-specific and detected only in a subset of tumors exhibiting the CpG island methylator phenotype (CIMP). Although the cause of altered patterns of DNA methylation in cancer remains unknown, it is believed that epidemiological factors, notably dietary folate intake, might strongly influence DNA methylation patterns. Recent studies further suggest that polymorphisms of genes involved in folate metabolism are causally related to the development of cancer. Identifying epidemiological factors responsible for epigenetic changes should provide clues for cancer prevention in the future.
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Metilação de DNA , Neoplasias Gastrointestinais/genética , Envelhecimento/fisiologia , Ilhas de CpG/fisiologia , Epigênese Genética/fisiologia , Ácido Fólico/fisiologia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/fisiopatologia , Inativação Gênica/fisiologia , Predisposição Genética para Doença , Humanos , Inflamação/fisiopatologia , Proto-Oncogene MasRESUMO
OBJECT: The goal of this study was to elucidate the genotype-phenotype relationship in syndromic craniosynostoses by analyzing the mutations of the fibroblast growth factor receptor (FGFR) gene and its clinical manifestations in patients, particularly those in atypical cases. METHODS: Twenty patients with craniosynostoses unrelated to Apert syndrome were enrolled in this study. The phenotypes indicated the following syndromes: 12 patients with unrelated Crouzon syndrome, including nine sporadic and three familial cases; two with sporadic Pfeiffer syndrome; and one with Antley-Bixler syndrome. The Crouzon phenotype was subdivided into three clinical forms: regular, top, and bottom ones. Two patients who demonstrated craniofacial anomalies and bilateral elbow joint contractures were categorized as having an unspecified craniosynostosis. Three cases of unclassifiable cloverleaf skull malformation were also analyzed. Fourteen mutations of the FGFR2 gene were identified in these patients; seven of the 10 cysteine-related mutations were substitutions of codon 342 in the third immunoglobulin-like domain of this gene. The phenotypes of these seven cases were three of regular Crouzon, two of unspecified craniosynostosis, and one each of top Crouzon and unclassifiable cloverleaf skull malformation. In addition, four of the seven patients were found to have the same genotype (Cys342Arg). The phenotypes of these patients, however, were quite variable, ranging from regular Crouzon to unclassifiable cloverleaf skull malformation. CONCLUSIONS: The phenotypes of patients with craniosynostoses unrelated to Apert syndrome proved quite variable, even in cases in which patients demonstrated the same genotype. In view of the phenotypic diversity evident in cases in which the same mutation in the FGFR2 gene is present, it is possible that other disease-modifying genetic factors exist to control the abnormal gain-of-function that accompanies FGFR signaling.