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BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large-scale pediatric-specific data regarding AMR treatment outcomes. METHODS: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1-18 years at transplant with biopsy-proven AMR between 2009 and 2019 and at least 12 months of follow-up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. RESULTS: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post-transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6-fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. CONCLUSIONS: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one-third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure.
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Transplante de Rim , Nefrologia , Humanos , Criança , Adolescente , Isoanticorpos , Rejeição de Enxerto/diagnóstico , Rim/patologia , Transplantados , Sobrevivência de EnxertoRESUMO
Primary papillary epithelial tumor of the sella (PPETS) is a newly described tumor entity with prototypical location in the sella. Only two case series with ten cases have been described so far. These tumours have a typical papillary architecture with bland nuclear features, TTF-1 immunopositivity and low MIB-1-labelling index. Many of these tumours were previously assigned under the category of 'ectopic choroid plexus papilloma'. PPETS expands the group of TTF-1 positive tumours of the central nervous system. Histomorphology plays an essential role in making this diagnosis. We report a case of 44-year-old female with a sellar mass lesion, who presented with progressive loss of vision and diagnosed as primary papillary epithelial tumor.
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Neoplasias Epiteliais e Glandulares , Papiloma do Plexo Corióideo , Feminino , Humanos , Adulto , Papiloma do Plexo Corióideo/diagnóstico , Papiloma do Plexo Corióideo/patologia , Sistema Nervoso Central/patologia , Diagnóstico Diferencial , Neoplasias Epiteliais e Glandulares/diagnóstico , Imageamento por Ressonância MagnéticaRESUMO
This cross-sectional study was carried out in the Department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2015 to June 2016 in collaboration with Department of Neurosurgery and Department of Pathology of same hospital, to assess MRI findings of common IMSCTs and to find out the validity of MRI in the diagnosis of spinal ependymoma and astrocytoma, thereby differentiating these two common intramedullary entities. For this purpose, 40 patients aged from 15 to 60 years, who were diagnosed or suspected cases of having intramedullary spinal cord tumours were enrolled. These patients underwent preoperative MRI for evaluation of the spinal cord tumours during the study period in department of Radiology and Imaging. Also, patients were diagnosed by MRI as having IMSCTs incidentally was included. All of them were followed by histopathological examination of the same lesions after surgery. Among these 40 patients after exclusion for valid reason 28 cases were included as study population. MR images were obtained on a 1.5 Tesla (Avanto Magnatom, Siemens) unit with a spine surface coil. MRI findings were compared with histopathology after surgery keeping histopathology as gold standard. Out of 28 clinically and MRI diagnosed IMSCTs cases, 19 cases of ependymoma, 8 cases of astrocytoma and one diagnosed as hemangioblastoma by MRI. The mean age was 34.11±9.55 years, ranging from 15 to 56 years for ependymoma, 26.88±8.08 years ranging from 16 to 44 years for astrocytoma. Highest incidence (47.4%) was in between 31 to 40 years for ependymoma, 50.0% were in between 21-30 for Astrocytoma. On MRI majority 12(63.2%) of the cord ependymomas and majority 5(62.5%) of astrocytomas were in cervical region. While considering axial location ependymomas are mostly 17(89.5%) central and astrocytomas 5(62.5%) are eccentric in location. It was observed that out of 19 cases of ependymoma more than half 10(52.6%) had elongated shape, 12(63.1%) had well defined margin. Associated syringohydromyelia was present in 16(84.2%) cases. On T1WI 11(57.9%) and 8(42.1%) cases were iso and hypo respectively. On T2WI 14(73.7%) cases were hyper intense. After Gd-DTPA in most cases, 13(68.4%) cases showed diffuse enhancement. Noticeable and sizeable solid component observed among 13(68.4%) of the cases. Hemorrhage with cap sign was found in more than one third 7(36.8%) cases. Out of 8 cases of astrocytomas 4(50.0%) had lobulated shape, ill-defined margin 5(62.5%). T1WI: Iso 5(62.5%), hypo 3(37.5%), T2WI: hyper 5(62.5%), After Gd-DTPA: focal and heterogenous enhancement 3(37.5%) and rim enhancement 4(50.0%). Component: mixed 4(50.0%), cystic 3(37.5%) and solid 1(12.5%). Hemorrhage without cap sign 2(25.0%), associated syringohydromyelia 1(12.5%). In the case of evaluation of intramedullary ependymoma sensitivity of MRI in the present series is 94.44%, specificity 80.0%, Positive predictive value (PPV) 89.5%, Negative predictive value (NPV) 88.9% and accuracy 89.28%. In case of MRI evaluation of intramedullary astrocytoma sensitivity of MRI in the present study is 85.71%, specificity 90.47%, PPV 75%, NPV 95% and accuracy 89.2%. Thus present study shows MRI is a sensitive and effective noninvasive imaging modality in diagnosing common intramedullary spinal cord tumours.
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Astrocitoma , Ependimoma , Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Adulto , Humanos , Adulto Jovem , Astrocitoma/diagnóstico por imagem , Bangladesh , Estudos Transversais , Ependimoma/diagnóstico por imagem , Gadolínio DTPA , Imageamento por Ressonância Magnética , Neoplasias da Medula Espinal/diagnóstico por imagem , Adolescente , Pessoa de Meia-IdadeRESUMO
PURPOSE: To create a high-quality, cadaver-based, operatively oriented resource documenting the anterior transcortical and interhemispheric transcallosal approaches as corridors to the third ventricle targeted towards neurosurgical trainees at all levels. METHODS: Two formalin-fixed, latex-injected specimens were dissected under microscopic magnification and endoscopic-assisted visualization. Dissections of the transcortical and transcallosal craniotomies with transforaminal, transchoroidal, and interforniceal transventricular approaches were performed. The dissections were documented in a stepwise fashion using three-dimensional photographic image acquisition techniques and supplemented with representative cases to highlight pertinent surgical principles. RESULTS: The anterior transcortical and interhemispheric corridors afford excellent access to the anterior two-thirds of the third ventricle with varying risks associated with frontal lobe versus corpus callosum disruption, respectively. The transcortical approach offers a more direct, oblique view of the ipsilateral lateral ventricle, whereas the transcallosal approach readily establishes biventricular access through a paramedian corridor. Once inside the lateral ventricle, intraventricular angled endoscopy further enhances access to the extreme poles of the third ventricle from either open transcranial approach. Subsequent selection of either the transforaminal, transchoroidal, or interforniceal routes can be performed through either craniotomy and is ultimately dependent on individual deep venous anatomy, the epicenter of ventricular pathology, and the concomitant presence of hydrocephalus or embryologic cava. Key steps described include positioning and skin incision; scalp dissection; craniotomy flap elevation; durotomy; transcortical versus interhemispheric dissection with callosotomy; the aforementioned transventricular routes; and their relevant intraventricular landmarks. CONCLUSIONS: Approaches to the ventricular system for maximal safe resection of pediatric brain tumors are challenging to master yet represent foundational cranial surgical techniques. We present a comprehensive operatively oriented guide for neurosurgery residents that combines stepwise open and endoscopic cadaveric dissections with representative case studies to optimize familiarity with third ventricle approaches, mastery of relevant microsurgical anatomy, and preparation for operating room participation.
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Neoplasias Encefálicas , Terceiro Ventrículo , Humanos , Criança , Terceiro Ventrículo/cirurgia , Terceiro Ventrículo/anatomia & histologia , Ventrículos Cerebrais/cirurgia , Ventrículos Cerebrais/anatomia & histologia , Procedimentos Neurocirúrgicos/métodos , Ventrículos Laterais/cirurgia , Neoplasias Encefálicas/cirurgia , Corpo Caloso/cirurgia , Corpo Caloso/anatomia & histologiaRESUMO
For three decades, the international Banff classification has been the gold standard for kidney allograft rejection diagnosis, but this system has become complex over time with the integration of multimodal data and rules, leading to misclassifications that can have deleterious therapeutic consequences for patients. To improve diagnosis, we developed a decision-support system, based on an algorithm covering all classification rules and diagnostic scenarios, that automatically assigns kidney allograft diagnoses. We then tested its ability to reclassify rejection diagnoses for adult and pediatric kidney transplant recipients in three international multicentric cohorts and two large prospective clinical trials, including 4,409 biopsies from 3,054 patients (62.05% male and 37.95% female) followed in 20 transplant referral centers in Europe and North America. In the adult kidney transplant population, the Banff Automation System reclassified 83 out of 279 (29.75%) antibody-mediated rejection cases and 57 out of 105 (54.29%) T cell-mediated rejection cases, whereas 237 out of 3,239 (7.32%) biopsies diagnosed as non-rejection by pathologists were reclassified as rejection. In the pediatric population, the reclassification rates were 8 out of 26 (30.77%) for antibody-mediated rejection and 12 out of 39 (30.77%) for T cell-mediated rejection. Finally, we found that reclassification of the initial diagnoses by the Banff Automation System was associated with an improved risk stratification of long-term allograft outcomes. This study demonstrates the potential of an automated histological classification to improve transplant patient care by correcting diagnostic errors and standardizing allograft rejection diagnoses.ClinicalTrials.gov registration: NCT05306795 .
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Transplante de Rim , Rim , Adulto , Humanos , Masculino , Feminino , Criança , Estudos Prospectivos , Rim/patologia , Transplante de Rim/efeitos adversos , Transplante Homólogo , Aloenxertos , Rejeição de Enxerto/diagnóstico , BiópsiaRESUMO
OBJECTIVE: Ecchordosis physaliphora (EP) is a non-neoplastic notochord remnant with limited literature. We present a review on surgically resected clival EP to evaluate if available follow-up is adequate to distinguish EP from chordomas. METHODS: A systematic literature review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Case reports or series of adults with histopathologic and radiographic findings of surgically resected EP were included. Articles including pediatric patients, systematic reviews, chordomas, and without microscopic or radiographic confirmation, or the surgical approach, were excluded. Corresponding authors were contacted twice to further evaluate outcomes. RESULTS: Eighteen articles were included (n = 25 patients; mean age 47.5 years ± 12.6 [standard deviation] months). All patients had symptomatic, surgically resected EP, with cerebrospinal fluid leak or rhinorrhea the most common symptom (48%). All but 3 had gross total resection, with endoscopic endonasal transsphenoidal transclival the most common approach (80%). All but 3 reported immunohistochemistry findings, with physaliphorous cells the most common. All but 5 patients had definitive follow-up (80%), with average of 19.5 ± 17.2 months. One corresponding author reported longer-term follow-up for 1 patient (57 months). No recurrence or malignant transformation was reported. Mean time to clival chordoma recurrence (53.9 ± 26.8 months) was also evaluated in a review of 8 studies. CONCLUSIONS: Mean follow-up for resected EP was almost 3 times shorter than mean time to recurrence of chordomas. Available literature is likely inadequate to confirm the suspected benign nature of EP especially in reference to chordoma, precluding treatment and follow-up recommendations.
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Cordoma , Hamartoma , Malformações do Sistema Nervoso , Adulto , Humanos , Criança , Pessoa de Meia-Idade , Seguimentos , Cordoma/diagnóstico por imagem , Cordoma/cirurgia , Fossa Craniana Posterior/cirurgia , Hamartoma/patologia , Vazamento de Líquido Cefalorraquidiano/patologia , Malformações do Sistema Nervoso/patologiaRESUMO
Heterotrimeric G proteins serve as membrane-associated signaling hubs, in concert with their cognate G-protein-coupled receptors. Fluorine nuclear magnetic resonance spectroscopy was employed to monitor the conformational equilibria of the human stimulatory G-protein α subunit (Gsα) alone, in the intact Gsαß1γ2 heterotrimer or in complex with membrane-embedded human adenosine A2A receptor (A2AR). The results reveal a concerted equilibrium that is strongly affected by nucleotide and interactions with the ßγ subunit, the lipid bilayer and A2AR. The α1 helix of Gsα exhibits significant intermediate timescale dynamics. The α4ß6 loop and α5 helix undergo membrane/receptor interactions and order-disorder transitions respectively, associated with G-protein activation. The αN helix adopts a key functional state that serves as an allosteric conduit between the ßγ subunit and receptor, while a significant fraction of the ensemble remains tethered to the membrane and receptor upon activation.
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Subunidades alfa Gs de Proteínas de Ligação ao GTP , Proteínas Heterotriméricas de Ligação ao GTP , Humanos , Modelos Moleculares , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Conformação Proteica , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Subunidades alfa de Proteínas de Ligação ao GTP/química , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Ligação ProteicaRESUMO
Acromegaly is a disease that occurs secondary to high levels of GH, most often from a hormone-secreting pituitary adenoma, with multisystem adverse effects. Diagnosis includes serum GH and IGF-1 levels, and obtaining an MRI pituitary protocol to assess for a functional pituitary adenoma. Attempted gross total resection of the GH-secreting adenoma is the gold standard in treatment for patients with acromegaly for a goal of biochemical remission. Medical and radiation therapies are available when patients do not achieve biochemical cure after surgical therapy.
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Acromegalia , Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Neoplasias Hipofisárias , Acromegalia/complicações , Acromegalia/cirurgia , Adenoma/complicações , Adenoma/cirurgia , Objetivos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Humanos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgiaRESUMO
PURPOSE: Traditional endoscopic endonasal approaches to the cavernous sinus (CS) open the anterior CS wall just medial to the internal carotid artery (ICA), posing risk of vascular injury. This work describes a potentially safer midline sellar entry point for accessing the CS utilizing its connection with the inferior intercavernous sinus (IICS) when anatomically present. METHODS: The technique for the midline intercavernous dural access is described and depicted with cadaveric dissections and a clinical case. RESULTS: An endoscopic endonasal approach exposed the periosteal dural layer of anterior sella and CS. The IICS was opened sharply in midline through its periosteal layer. The feather knife was inserted and advanced laterally within the IICS toward the anterior CS wall, thereby gradually incising the periosteal layer of the IICS. The knife was turned superiorly then inferiorly in a vertical direction to open the anterior CS wall. This provided excellent access to the CS compartments, maintained the meningeal layer of the IICS and the medial CS wall, and avoided an initial dural incision immediately adjacent to the ICA. CONCLUSION: The midline intercavernous dural access to the CS assisted by a 90° dissector-blade is an effective modification to previously described techniques, with potentially lower risk to the ICA.
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Seio Cavernoso , Cadáver , Seio Cavernoso/cirurgia , Humanos , NarizRESUMO
Background: Tuberculum sellae meningiomas represent approximately 5-10% of intracranial meningiomas.[2] Although benign, they are associated with substantial morbidity, especially visual disturbance. At present, there are three main treatment options for patients with tuberculum sellae meningiomas: observational, with serial imaging follow; microsurgical resection; and stereotactic radiosurgery. The advantages of the supraorbital eyebrow craniotomy are the direct visualization of the anterior cranial fossa, anterior circulation, and the optical apparatus, reducing the extent of brain retraction, and the absence of risks of temporalis muscle hypotrophy and posterior chewing discomfort. Conversely, minor drawbacks are a steeper learning curve related to a narrower surgical corridor than a standard frontotemporal approach and the minimal risk of supraorbital nerve injury.[1,3]. Case Description: The authors report the case of a 42-year-old female who presented with acute-onset vision loss and only finger counting in her left eye associated with headache. Magnetic resonance imaging (MRI) showed a suprasellar extra-axial T1 enhancing mass with encasement of the left optic nerve and paraclinoid internal carotid artery and mass effect on the optic chiasm. A keyhole supraorbital eyebrow approach assisted with a microinspection tool was performed for tumor resection and optic nerve decompression. A Simpson Grade 2 tumor resection was achieved, and histopathology revealed a WHO Grade-I tuberculum sellae meningioma. The patient's presentation, rationale, key surgical steps, and outcome are discussed, and informed consent for surgery and video recording was obtained. Conclusion: This surgical video illustrates the use of a keyhole supraorbital eyebrow approach assisted with a microinspection endoscopic tool for the resection of a tuberculum sellae meningioma. The tumor size, extension, and preoperative clinical status determine the optimal surgical corridor in tuberculum sellae meningioma. The keyhole supraorbital eyebrow approach allows safe and direct access to anterior cranial fossa lesions.
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Cushing disease is a disorder of hypercortisolemia caused by hypersecretion of adrenocorticotropic hormone by a pituitary adenoma and is a rare diagnosis. Cushing disease presents with characteristic clinical signs and symptoms associated with excess cortisol, but diagnosis is difficult and often relies on repeated and varied endocrinologic assays and neuroradiologic investigations. Gold standard treatment is surgical resection of adrenocorticotropic hormone-secreting pituitary adenoma, which is curative. Patients require close endocrinologic follow-up for maintenance of associated neuroendocrine deficiencies and surveillance for potential recurrence. Medications, radiation therapy, and bilateral adrenalectomy are alternative treatments for residual or recurrent disease.
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Adenoma Hipofisário Secretor de ACT , Adenoma , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/cirurgia , Humanos , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgiaRESUMO
Nocturnal enuresis is a common symptom in children with sickle cell disease (SCD). Risk factors for development of enuresis are currently unknown. An early manifestation of SCD-associated kidney damage is glomerular hyperfiltration. We test the hypothesis that in a pediatric SCD cohort, individuals with hyperfiltration are more likely to have nocturnal enuresis when compared to children without hyperfiltration. To assess the relationship between nocturnal enuresis and hyperfiltration, we retrospectively evaluated children with SCD enrolled in the Evaluation of Nocturnal Enuresis and Barriers to Treatment among Pediatric Patients with SCD study and prospectively identified children who reported nocturnal enuresis and were enrolled in the longitudinal cohort study Sickle Cell Clinical Research and Intervention Program. Nocturnal enuresis occurred in 46.5% of Pediatric Patients with Sickle Cell Disease participants and was more frequent in participants with HbSS/HbSß 0 thalassemia and in male participants. We did not identify an association between hyperfiltration from 3 to 5 years of age with the later development of enuresis. Severe SCD genotypes and male sex were associated with nocturnal enuresis after age 5 years. We could not identify additional renal or hematologic predictors associated with the diagnosis of nocturnal enuresis. Future studies should incorporate nonrenal risk factors into studies that predict development of enuresis.
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Anemia Falciforme , Nefropatias , Enurese Noturna , Anemia Falciforme/complicações , Criança , Pré-Escolar , Feminino , Humanos , Nefropatias/complicações , Estudos Longitudinais , Masculino , Enurese Noturna/complicações , Enurese Noturna/etiologia , Estudos RetrospectivosRESUMO
Minimally invasive trans-sulcal parafascicular port-based approaches can provide safe access to a wide variety of deep brain lesions.1,2 This surgical video illustrates the use of a minimally invasive port-based approach for resection of a subcortical right medial occipital lobe lesion in a 63-year-old woman who presented with seizures and bilateral left homonymous hemianopia. MRI showed a 2.5-cm contrast enhancing lesion with a necrotic center and significant T2 and fluid-attenuated inversion recovery signal consistent with vasogenic edema. Diffusion tensor imaging revealed compromise of the right optic radiations and edema extending through the right corticospinal tract. A minimally invasive trans-sulcal parafascicular port-based approach to the deep occipital lobe and periatrial region was performed under full exoscopic visualization. A gross total tumor resection was achieved, and histopathology revealed an IDH1-mutant, MGMT-methylated-positive glioblastoma. The patient's presentation, rationale, key surgical steps, and outcomes are discussed, and informed consent for surgery was obtained. The participants and any identifiable individuals consented to the publication of their image. Images at 3:50 used with permission from Nico Corporation. All rights reserved.
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OBJECTIVE: To delineate the steps of exoscopic en bloc carotid artery-sparing total temporal bone resection for malignancies involving the temporal bone in a cadaveric model. METHODS: Dissections were performed on 3 right-sided (3 sides) formalin-fixed, latex-injected cadaveric specimens. An exoscopic en bloc carotid artery-sparing total temporal bone resection was performed on each cadaver. In the past 4 years, 8 patients have undergone exoscope-assisted internal carotid artery-sparing total temporal bone resection with the technique described in this report. As an example, we present a representative case of a patient in whom this technique was used. RESULTS: Exoscope-assisted en bloc total temporal bone resections were performed on 3 right-sided cadaveric specimens. The following steps were described to circumferentially expose the petrous temporal bone: infratemporal fossa exposure, temporal craniotomy for subtemporal middle fossa approach to the petrous bone, retrosigmoid craniotomy, and transjugular approach. Finally, 3 skull base osteotomies were performed to liberate anterior, medial, posterior attachments of the petrous bone for en bloc removal. Possible extensions of these dissections as indicated by tumor pathology were described. A case illustration and operative video utilizing these techniques is presented. CONCLUSIONS: Exoscope-assisted en bloc carotid artery-sparing total temporal bone resection is a feasible technique for management of malignancies with temporal bone invasion.
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Osso Petroso , Osso Temporal , Artérias Carótidas/cirurgia , Craniotomia/métodos , Estudos de Viabilidade , Humanos , Osso Petroso/cirurgia , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgiaRESUMO
Oral squamous cell carcinoma, one of the most common malignancies, has a poor prognosis due to impairment in oral functions secondary to treatment. Trismus one of the major causes of impairment of oral function. The present study investigated the prevalence of trismus and its impact on oral health-related quality of life (OHRQoL) in patients treated for oral squamous cell carcinoma (OSCC). The maximum inter-incisal mouth opening of hundred OSCC patients was recorded at post-treatment and 3 months post-treatment. OHRQoL questionnaire (OHIP-14) was intervened to assess the OHRQoL of patients post-treatment and 3 months follow-up, with emphasis on correlation with grades of trismus. The prevalence of trismus was 16% pre-treatment, 72% post-treatment, and 62% at 3 months after treatment. The overall OHIP-14 scores indicated that patients with trismus reported greater impairment of OHRQoL than those without trismus at the end of treatment and 3 months follow-up. At the end of treatment, patients with severe trismus demonstrated a higher mean OHIP-14 score (23.47 ±3.34) than those with moderate (17.72 ±2.83) and mild trismus (12.66 ±3.84) with statistically significant differences (p <0.001). Equivalent results were obtained at 3 months follow-up period. Patients with trismus suffer greater impairment of OHRQoL. The findings demand the need of identifying risk factors for developing trismus and early institution of newer/modified treatment approaches for better OHRQoL in OSCC survivors.
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Carcinoma de Células Escamosas/terapia , Neoplasias Bucais/terapia , Saúde Bucal , Qualidade de Vida , Trismo/epidemiologia , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Prevalência , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários , Taxa de Sobrevida , Trismo/psicologiaRESUMO
Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyze 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlight the very early origins of LMS. We uncover three specific subtypes of LMS that likely develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynecological origin harbor genomic dystrophin deletions and/or loss of dystrophin expression, acquire the highest burden of genomic mutation, and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP trappers and other DNA damage response inhibitors, suggesting a promising therapeutic strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis.
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Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença/genética , Genômica/métodos , Leiomiossarcoma/genética , Músculo Liso/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Evolução Clonal , Estudos de Coortes , Feminino , Humanos , Leiomiossarcoma/classificação , Leiomiossarcoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Músculo Liso/patologia , Mutação , RNA-Seq/métodos , Análise de SobrevidaRESUMO
OBJECTIVE: The objective of the present study was to describe and evaluate the feasibility, mobility, and surface area provided by the simple and extended transorbital pericranial flap (TOPF). Furthermore, we compared this novel technique with the current practice of pericranial flap harvesting and insetting techniques. We also studied the adequacy of the TOPF in the reconstruction of postoperative anterior cranial fossa (ACF) defects. METHODS: The TOPF was performed bilaterally in 5 alcohol-preserved, latex-injected human cadaveric specimens. The TOPF was harvested in 2 stages: the orbitonasal stage and the cranial stage. For the orbitonasal stage, a transorbital superior eyelid approach was used. We have described 2 harvesting techniques for creating 2 distinct TOPF types (simple and extended) according to the main vascular pedicle. The superficial flap areas offered by the simple and extended TOPF and the traditional bicoronal pericranial flap were calculated and compared. The distances from the supratrochlear and supraorbital arteries to specified anatomical landmarks were also measured. Additionally, the ACF defect area of relevant surgical cases performed using endoscopic transcribriform approaches were measured on immediate postoperative computed tomography head scans using radiological imaging software. RESULTS: The harvest of both the simple and the extended TOPFs was efficient. As expected, the areas offered by simple and extended TOPFs were smaller than that offered by the traditional bicoronal flap. However, the surface area offered by either the simple or extended TOPF provides sufficient coverage for most ACF defects. A high spatial distribution was observed between the vascular pedicles and their respective foramen or notch. CONCLUSIONS: The TOPF represents a novel harvesting, tunneling, and insetting technique that offers a large, versatile, pedicled flap for coverage of most standard ACF defects after endoscopic surgery.
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Procedimentos Neurocirúrgicos/métodos , Órbita/cirurgia , Retalhos Cirúrgicos , Adulto , Pontos de Referência Anatômicos , Cadáver , Fossa Craniana Anterior/cirurgia , Endoscopia/métodos , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/cirurgia , Órbita/anatomia & histologia , Procedimentos de Cirurgia Plástica/métodos , Base do Crânio/anatomia & histologia , Base do Crânio/cirurgia , Tomografia Computadorizada por Raios X , Transplante AutólogoRESUMO
INTRODUCTION: Rabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a "standard" higher dose. METHODS: We performed a retrospective multicenter study of all isolated first-time kidney transplant recipients <21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (> 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival. RESULTS: Two hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07). CONCLUSION: A low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.
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BACKGROUND: Modern aggressive oncological treatment options for oral squamous cell carcinoma (OSCC) are inevitably associated with impaired general health-related quality of life (HRQoL) and oral HRQoL (OHRQoL). However, there is dire need for prospective and concomitant assessment of HRQoL and OHRQoL after different treatment regims. Hence, present study was designed to investigate HRQoL and OHRQoL in patients treated for OSCC using various modalities. METHODS: 135 OSCC patients were grouped according to treatment rendered into Group A: surgery only; Group B: post-surgical radiotherapy (PRT); and Group C: post-surgical chemo-radiation (PCRT). The 12-item Short Form Health Survey (SF-12) and Oral Health Impact Profile-14 (OHIP-14) were intervened to assess HRQoL and OHRQoL respectively at 1-month and 6-months post-treatment. RESULTS: At 1-month post-treatment, patients who received PCRT showed significantly lower mean values for physical and mental domains of SF-12 and higher mean subscales and overall OHIP-14 (24.57 â± â2.62) score than those treated by surgery alone (10.55 â± â2.26) and PRT (20.20 â± â3.80), with largest differences between PCRT and surgery alone groups (p â< â0.001). Social functioning, general health and bodily pain of SF-12 and functional limitations, physical pain and physical disability amongst OHIP-14 domains were greatly affected. Although few physical domains of SF-12 showed significant improvement, mental domains remained a greater problem after 6 months. However, OHRQoL was significantly poor in all the three study groups (p â< â0.001). CONCLUSION: Irrespective of the post-treatment duration, patients who received PCRT had worse HRQoL and OHRQoL. There is a need to identify factors associated with impaired HRQoL and OHRQoL to customize better therapeutic decisions.
RESUMO
Among all the viral infections, acquired immunodeficiency syndrome (AIDS) is considered as one of the most morbid infections caused by the human immunodeficiency virus (HIV). The prime reason for the pathogenesis is the profound immunosuppression that leads to lethal opportunistic infections (OI), neurological disorders, unexpected malignancies and pathologies of the orofacial region. Patients with OI whose HIV status is unknown have shown a mortality rate higher than those with known HIV status. Among HIV-associated infections, orofacial lesions contribute a major proportion of the OI attributed to the plethora of micro-organisms present in the oral cavity. Apart from serious clinical manifestations, opportunistic infections also lead to significant impairment of quality of life. These lesions not only indicate the HIV infection but also among the clinical manifestations, which often occur early in the course of disease. World Health Organization has also provided policies for treatment/prevention of oral lesions, strengthening the promotion and care of oral health in HIV/AIDS patients. The present review provides comprehensive information about orofacial OI in HIV/AIDS patients and emphasis was also given to the malignancies associated with EB and HTLV virus.