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1.
Clin Cancer Res ; 28(4): 689-696, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34862245

RESUMO

PURPOSE: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line. PATIENTS AND METHODS: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, ≤ 4-mg dexamethasone daily dose, and Karnofsky score ≥70. Vaccine treatment consisted of two phases: an induction phase with vaccine given weekly for 4 weeks, and a maintenance phase with vaccines administered every 8 weeks until depletion of supply or disease progression. Patients with newly diagnosed GBM also received standard-of-care radiation and temozolomide. The primary objective for this open-label, single-institution trial was to assess the safety and tolerability of the autologous DC vaccine. RESULTS: For the 11 patients with newly diagnosed GBM, median progression-free survival (PFS) was 8.75 months, and median overall survival was 20.36 months. For the 25 patients with recurrent GBM, median PFS was 3.23 months, 6-month PFS was 24%, and median survival was 11.97 months. A subset of patients developed a cytotoxic T-cell response as determined by an IFNγ ELISpot assay. CONCLUSIONS: In this trial, treatment of newly diagnosed and recurrent GBM with autologous DC vaccine pulsed with lysate derived from an allogeneic stem-like cell line was safe and well tolerated. Clinical outcomes add to the body of evidence suggesting that immunotherapy plays a role in the treatment of GBM.


Assuntos
Neoplasias Encefálicas , Vacinas Anticâncer , Glioblastoma , Transplante de Células-Tronco Hematopoéticas , Neoplasias Encefálicas/patologia , Linhagem Celular , Células Dendríticas , Glioblastoma/patologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico
2.
J Clin Neurosci ; 89: 158-160, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34119261

RESUMO

Intracranial myeloid sarcoma (IMS) is a rare central nervous system manifestation of hematopoietic neoplasms of myeloid origin. We report the first case of IMS treatment with an isocitrate dehydrogenase-2 (IDH-2) inhibitor, Enasidenib, following surgical resection, whole-brain radiation, and consolidation Etoposide/Cytarabine therapy. A 42-year-old female was diagnosed with IMS after a 10-year remission of her acute myeloid leukemia (AML). She underwent surgical debulking and had postoperative resolution of her visual symptoms. She received adjuvant radiation and medical management, and continues to show no evidence of recurrence or progression at 17 months postoperatively. This case is notable for an isolated IMS presentation in a patient with a very distant history of AML remission, and without evidence of concurrent bone marrow relapse. The goals of neurosurgical intervention should be symptomatic relief of mass effect and pathological diagnosis, due to the sensitivity of IMS to adjuvant radiation and medical management such as IDH-2 inhibitors.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/terapia , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/terapia , Adulto , Aminopiridinas/administração & dosagem , Citarabina/administração & dosagem , Feminino , Humanos , Quimioterapia de Indução/métodos , Indução de Remissão/métodos , Triazinas/administração & dosagem
3.
World Neurosurg ; 148: 29-37, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33444829

RESUMO

OBJECTIVE: Intracranial myeloid sarcomas (IMS) are rare central nervous system manifestations of malignant hematopoietic neoplasms of myeloid origin such as acute myeloid leukemia and chronic myeloid leukemia. Reported cases in the literature are limited to primarily case reports. We present a systematic review of this rare central nervous system tumor, characterizing the clinical presentation, tumor location, histopathology, and available treatment modalities. We correlate these variables with mortality, recurrence, and complications to suggest optimal management strategies for IMS. METHODS: A systematic literature search was performed across Ovid MEDLINE, Scopus, and Embase using 14 search terms in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This systematic review examines variables such as patient age, tumor location, size, presenting symptoms, treatment modality, extent of resection, and mortality. We performed descriptive analyses to identify bivariate associations between patient characteristics, treatment, and outcomes. RESULTS: The mean age at diagnosis was 34.8 years, and the most common etiology was acute myeloid leukemia (68.8%). The most common presenting symptoms were headache (45.5%), vision complaints (27.3%), and weakness/motor symptoms (21.2%). IMS were most commonly located in the temporal lobe (10.1%), cerebellum (10.1%), or falcine/parasagittal (10.1%) region. Patients who received radiotherapy (P < 0.001) or chemotherapy (P < 0.001) had lower rates of mortality versus those who did not. Surgical treatment and extent of resection were not significantly associated with mortality (P > 0.05). CONCLUSION: The use of adjuvant radiotherapy or chemotherapy for IMS significantly reduces mortality, confirming IMS as a cranial manifestation of a systemic disease. Although surgical treatment is indicated for histopathologic diagnosis and to relieve mass effect, the extent of resection does not predict overall survival.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Procedimentos Neurocirúrgicos/métodos , Radioterapia/métodos , Sarcoma Mieloide/terapia , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/fisiopatologia , Quimioterapia Adjuvante , Cefaleia/fisiopatologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mieloide Aguda/complicações , Debilidade Muscular/fisiopatologia , Recidiva Local de Neoplasia , Radioterapia Adjuvante , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/fisiopatologia , Taxa de Sobrevida , Resultado do Tratamento , Transtornos da Visão/fisiopatologia
4.
Clin Neurol Neurosurg ; 201: 106405, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33340839

RESUMO

INTRODUCTION: Gangliogliomas rarely occur in the sella or suprasellar region and are almost never seen in the pituitary stalk. Seven cases of gangliogliomas occurring in this region have been reported; only one case involved a tumor within the pituitary stalk. Of the six tumors external to the pituitary stalk, two occurred in the neurohypophysis, one was in the adenohypophysis, the location of one was unspecified, and two extensively invaded the optic chiasm, hypothalamus and brainstem. This is only the second reported case of a pituitary stalk ganglioglioma, and it is unique in its use of an extended endoscopic endonasal approach for biopsy. CASE REPORT: A 51-year old woman presented with an eleven-month history of polydipsia and polyuria leading to the diagnosis of diabetes insipidus. Magnetic Resonance Imaging of the brain revealed contrast-enhanced thickening and anterior bowing of the hypophyseal stalk. An extended endoscopic endonasal approach permitted midline removal of the tuberculum sella, opening of underlying dura, and exposure of the pituitary stalk. A firm, white, 4 mm diameter mass, integral to the right side of the enlarged pituitary stalk was seen and biopsied. Histopathological analysis was consistent with WHO grade 1 ganglioglioma. The patient tolerated the procedure well and required no endocrinologic treatment other than desmopressin. CONCLUSION: Pituitary stalk gangliogliomas are extremely rare. The diagnosis should be considered in patients with pituitary stalk enlargement. Endoscopic endonasal approach is a safe surgical approach to establish a tissue diagnosis which is essential for pathologic certainty given the wide differential diagnosis of stalk lesions.


Assuntos
Neoplasias Encefálicas/cirurgia , Ganglioglioma/cirurgia , Hipófise/cirurgia , Neoplasias Hipofisárias/cirurgia , Neoplasias Encefálicas/patologia , Diabetes Insípido/complicações , Diabetes Insípido/diagnóstico , Dura-Máter/patologia , Dura-Máter/cirurgia , Feminino , Ganglioglioma/diagnóstico , Humanos , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico
5.
Clin Neurol Neurosurg ; 199: 106283, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33069929

RESUMO

BACKGROUND: Primary intraosseous meningiomas (PIM) of calvarial origin are a small subset of meningiomas that arise from and occur within the calvarial bone. Its definition is often confused with other forms of non-dural based intracranial meningiomas, which has made previously published retrospective reviews heterogenous, non-specific and sometimes inaccurate. We present a systematic review of calvarial PIM. METHODS: Using a systematic search protocol that included databases such as PubMed, Web of Science and Embase, we extracted all human studies on PIM published from inception to December 2017. This systematic review includes case reports and retrospective reviews that specifically described PIM. RESULTS: On review of 166 articles identified with the systematic search protocol, 69 articles were analyzed. These comprised of 64 case reports, 1 case series and 4 retrospective reviews. 111 patients with PIM of calvarial origin were analyzed, 58 % of which were females and 42 % males. The mean patient age was 51 years and the frontal bone was the most common tumor location, occurring in 26.1 % of the cases. Surgical resection was the predominant modality of treatment in 97.2 % of the cases, and gross total resection was achieved in 84 % of cases that reported extent of resection. There were no recurrences for grade I meningiomas. However, all grade III meningiomas recurred and 33.3 % of grade II meningiomas showed recurrence with a mean postoperative follow-up interval of 20 months. Statistical analysis using Fisher's exact test showed the recurrence rate to be strongly associated with WHO tumor grade (p-value <0.001). CONCLUSION: There is statistically significant increased recurrence rate for calvarial PIM of higher grades, and we recommend close follow-up in those cases. Surgical resection remains the overwhelming treatment of choice for calvarial PIM, and it has a high gross total resection rate and low risk of complications and mortality.


Assuntos
Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Neoplasias Cranianas/diagnóstico por imagem , Crânio/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Meníngeas/terapia , Meningioma/terapia , Estudos Retrospectivos , Neoplasias Cranianas/terapia , Tomografia Computadorizada por Raios X/métodos
7.
J Clin Neurosci ; 78: 416-417, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32362469

RESUMO

Implantable intrathecal infusion pumps (ITPs) are an effective pain management modality for patients who have failed non-operative options. We present the first report of asymptomatic intracranial subarachnoid fat dissemination secondary to an ITP. A 39-year-old who underwent implantation of an ITP for intractable pelvic pain developed altered mental status. CT and MRI revealed subarachnoid fat deposition without evidence of a dermoid or epidermoid cyst. She returned to her baseline mental status with her symptoms attributed to delirium. The rare possibility of subarachnoid fat dissemination following transdural spinal procedures should be considered as a potential complication of ITPs. Although fat may persist in the subarachnoid space for years, asymptomatic patients can be safely managed with observation alone.


Assuntos
Tecido Adiposo/crescimento & desenvolvimento , Bombas de Infusão Implantáveis/efeitos adversos , Espaço Subaracnóideo/patologia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Adulto , Cisto Epidérmico , Feminino , Humanos , Injeções Espinhais/efeitos adversos , Imageamento por Ressonância Magnética , Manejo da Dor , Dor Intratável/terapia , Espaço Subaracnóideo/diagnóstico por imagem
8.
World Neurosurg ; 137: 94-97, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32006734

RESUMO

BACKGROUND: Elevation of bone for the treatment of depressed skull fractures overlying venous sinuses is rarely required or performed. The neurosurgical literature only describes a handful of cases of surgical intervention in which the posterior two-thirds of the superior sagittal sinus was involved. Clinical course is variable, signs and symptoms suggest increased intracranial pressure, and all conservative measures should be exhausted before proceeding with the surgical route. CASE DESCRIPTION: A 27-year-old man presented with a self-inflicted gunshot wound to posterior head. On presentation, there were no neurologic complaints. On imaging, the bullet fragment was associated with a comminuted anteriorly displaced fracture over the torcula. Vessel imaging showed tapering of the superior sagittal sinus and transverse sinuses near the torcula, suggesting narrowing due to mass effect. The patient did not respond to initial conservative management and developed worsening diplopia and papilledema concerning for increased intracranial pressure. Occipital/suboccipital craniectomy was performed with elevation of depressed skull fracture, decompression of dural venous sinus, removal of bullet, and mesh cranioplasty. Repeat ophthalmology examination postoperatively showed improvement in optic disc edema and diplopia. CONSLUSIONS: This case confirms that the approach of surgical management of superior sagittal venous sinus injuries associated with skull fractures described in the literature also can be used successfully for injuries over the torcula if conservative management does not help alleviate the symptoms and results in good outcome. It was felt that delayed surgery also plays an important role, as it gives time for scar tissue to form, which may help to protect the sinus from injury during surgery.


Assuntos
Cavidades Cranianas/cirurgia , Hipertensão Intracraniana/cirurgia , Ferimentos por Arma de Fogo/cirurgia , Adulto , Cavidades Cranianas/lesões , Humanos , Hipertensão Intracraniana/diagnóstico , Hipertensão Intracraniana/etiologia , Masculino , Papiledema/diagnóstico , Papiledema/cirurgia , Fraturas Cranianas/complicações , Fraturas Cranianas/cirurgia , Seio Sagital Superior/cirurgia , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/diagnóstico
9.
World Neurosurg ; 136: 184-186, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31917313

RESUMO

Enthusiasm for research and teaching are often the main reasons neurosurgical residents choose academic careers, and subspecialty choice usually stems from an interest in that particular field. However, recent salary data bring to light a work relative value unit-related trend in American academic neurosurgeon salaries, one that is similar to private practice, where compensation is strongly correlated with clinical productivity. In addition, there are significant disparities in how various subspecialties are remunerated in academic settings. For example, functional and pediatric specialists earn significantly lower salaries on average compared with their spine and endovascular colleagues. These trends have important implications both for neurosurgical trainees and for institutions in the United States.


Assuntos
Neurocirurgia/economia , Neurocirurgia/tendências , Salários e Benefícios/tendências , Humanos , Fatores Socioeconômicos , Estados Unidos
10.
J Biomed Res ; 34(4): 318-322, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32701070

RESUMO

Intraventricular metastases are a rare occurrence, particularly from a primary colorectal malignancy. To our knowledge, this is the first report of intraventricular metastasis from rectal cancer. A 72-year-old male presented with a new diagnosis of multiple intraventricular lesions, an anterior mediastinal mass and a rectal mass. His workup revealed rectal adenocarcinoma with intraventricular metastases and an incidental thymoma. Ommaya reservoir placement was performed via an awake procedure rather than under general anesthesia due to airway concerns. Cerebrospinal fluid (CSF) cytology was positive for malignancy and consistent with adenocarcinoma. Two weeks postoperatively, the patient underwent whole brain radiation. Although rare, this diagnosis should always be considered in the differential for solitary or multiple intraventricular lesions. CSF sampling is a useful alternative to intraventricular biopsy for diagnosis of intraventricular metastases. Awake placement of Ommaya reservoir is a safe option in the management of patients with intraventricular metastases, especially those who cannot undergo general anesthesia.

11.
Neurosurgery ; 83(6): E221-E225, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29294115

RESUMO

BACKGROUND AND IMPORTANCE: Intracranial cerebral aneurysms secondary to neoplastic etiology are a very rare occurrence. There have only been 5 published reports of intracranial cerebral aneurysms secondary to metastatic lung cancer. Four of those five previously published reports have been secondary to nonsmall cell lung carcinoma, and only 1 case caused subarachnoid hemorrhage. To our knowledge, this is the first report of a lung cancer-associated superior cerebellar artery aneurysm. CLINICAL PRESENTATION: A 41-yr old male presented with right-sided cerebellar hemorrhage. Cerebral angiogram was negative, but he was noted to have an underlying nonsmall cell carcinoma. His workup revealed a left upper lobe mass consistent with a diagnosis of metastatic lung carcinoma. A few weeks later, the patient represented with subarachnoid hemorrhage from a left superior cerebellar artery aneurysm that was new in comparison with a magnetic resonance angiography 19 d earlier. The aneurysm was remote to the surgical site, and the patient had a negative infectious workup, making an iatrogenic pseudoaneurysm or mycotic aneurysm unlikely. In the setting of metastatic cancer, a neoplastic cerebral aneurysm was the presumptive diagnosis. CONCLUSION: Intracranial neoplastic cerebral aneurysms are extremely rare entities, and a rare cause of subarachnoid hemorrhage. This diagnosis should be considered in patients who present with concurrent metastatic cancer and cerebral aneurysm or aneurysmal subarachnoid hemorrhage. Early initiation of chemotherapy may be beneficial in reducing the risk of tumor-particle embolization, but more research needs to be conducted to better understand this rare phenomenon.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/patologia , Neoplasias Pulmonares/patologia , Adulto , Humanos , Masculino , Hemorragia Subaracnóidea/etiologia
12.
Jt Comm J Qual Patient Saf ; 43(12): 633-641, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29173283

RESUMO

BACKGROUND: Health care providers routinely undertreat tobacco dependence, indicating a need for innovative ways to increase delivery of evidence-based care. Lean, a set of quality improvement (QI) tools used increasingly in health care, can help streamline processes, create buy-in for use of evidence-based practices, and lead to the identification of solutions on the basis of a problem's root causes. To date, no published research has examined the use of Lean tools in tobacco dependence. A 12-month QI project using Lean tools was conducted to increase delivery of evidence-based tobacco use treatment (TUT) to hospitalized neurosurgical patients. METHODS: The study team developed a nicotine replacement therapy (NRT) and counseling protocol for neurosurgery inpatients who indicated current tobacco use and used Lean tools to increase protocol adherence. Rates of NRT prescription, referrals to counseling, and follow-up phone calls were compared pre- and postintervention. Secondary measures included patient satisfaction with intervention, quit rates, and reduction rates at 4 weeks postdischarge. RESULTS: Referrals to counseling doubled from 31.7% at baseline to 62.0% after implementation of the intervention, and rates of nicotine replacement therapy (NRT) prescriptions during hospitalization and at discharge increased from 15.3% to 28.5% and 9.0% to 19.3%, respectively. Follow-up phone call rates also dramatically increased. The majority of satisfaction survey respondents indicated that counseling had a positive or neutral impact on stress level and overall satisfaction. CONCLUSION: Lean tools can dramatically increase use of evidence-based TUT in hospitalized patients. This project is easily replicable by professionals seeking to improve delivery of tobacco treatment. These findings may be particularly helpful to inpatient surgical departments that have traditionally been reticent to prescribe NRT.


Assuntos
Aconselhamento/organização & administração , Pacientes Internados , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de Tabaco , Tabagismo/terapia , Gestão da Qualidade Total/organização & administração , Centros Médicos Acadêmicos , Adulto , Idoso , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Melhoria de Qualidade/organização & administração , Encaminhamento e Consulta
13.
World Neurosurg ; 104: 205-212, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28457931

RESUMO

OBJECTIVE: To evaluate the clinical and angiographic outcomes of intracranial aneurysm treatment using a single Pipeline embolization device (PED), and to evaluate the factors affecting aneurysm obliteration rate. METHODS: The demographic characteristics and anatomic features of 58 aneurysms in 47 patients treated with a single PED were reviewed retrospectively. All aneurysms treated with a PED at a single center and with follow-up angiograms for at least 6 months were included in this study. RESULTS: The overall rate of complete and near-complete occlusion was 84% (49 of 58) after a mean follow-up period of 18.3 months. The rate of complete aneurysm obliteration was lower in aneurysms with an arterial branch arising from the aneurysm neck compared with aneurysms without an arterial branch (13% [1 of 8] vs. 68% [34 of 50]; P = 0.0075). The overall rate of complete and near-complete aneurysm occlusion was 90% (45 of 50) in aneurysms without an arterial branch arising from its neck. There were no statistically significant associations between obliteration rate and aneurysm neck width, size, or type, or history of previous coil embolization. CONCLUSIONS: Our data suggest that a single PED is sufficient to induce complete or near-complete obliteration of most aneurysms. The presence of a branching artery arising from the aneurysm neck is highly predictive of incomplete occlusion after treatment with a single PED.


Assuntos
Embolização Terapêutica/instrumentação , Embolização Terapêutica/estatística & dados numéricos , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/terapia , Distribuição por Idade , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Resultado do Tratamento
14.
World Neurosurg ; 89: 26-32, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26806066

RESUMO

OBJECTIVE: The purpose of this study was to explore the endoscopic endonasal approach to the anterior communicating artery complex. DESIGN: Anatomic, morphometric analysis of human cadaver heads. SUBJECTS: Fifteen latex-injected adult cadaver heads. MAIN OUTCOME MEASURES: The anatomic boundaries of the operative field and the dimensions of exposure of the anterior communicating artery (ACoA) complex were measured and clip placement feasibility was assessed. RESULTS: Exposure of the ACoA and bilateral A1 and A2 segments was accomplished in all 15 cadaver heads. Average length of the exposed ACoA was 3 ± 1 mm, the left A1 was 5 ± 3 mm and right A1 was 5 ± 1 mm, while the A2 segment was 5 ± 2 mm bilaterally. The average distance from the alar floor to the ACoA was 95 mm, while proximal lateral limit measured between the alar floor margins was 36 mm. The distal lateral limit as defined by the distance between the lateral most exposed margins of the chiasm was 19 mm. Clip placement was accomplished for the ACoA and the A1 and A2 segments bilaterally in all specimens. CONCLUSION: The endoscopic, endonasal transtuberculum, transplanum approach is an anatomically feasible alternative to treating select aneurysms of the ACoA complex.


Assuntos
Artérias Cerebrais/anatomia & histologia , Artérias Cerebrais/cirurgia , Aneurisma Intracraniano/cirurgia , Neuroendoscopia/métodos , Artérias Cerebrais/patologia , Estudos de Viabilidade , Humanos , Aneurisma Intracraniano/patologia , Nariz , Instrumentos Cirúrgicos
15.
BMC Cancer ; 12: 389, 2012 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-22950808

RESUMO

BACKGROUND: Lower concentrations of the insulin-like growth factor binding protein-1 (IGFBP-1) and elevated concentrations of insulin or C-peptide have been associated with an increase in colorectal cancer risk (CRC). However few studies have evaluated IGFBP-1 and C-peptide in relation to adenomatous polyps, the only known precursor for CRC. METHODS: Between November 2001 and December 2002, we examined associations between circulating concentrations of insulin, C-peptide, IGFBP-1 and apoptosis among 190 individuals with one or more adenomatous polyps and 488 with no adenomatous polyps using logistic regression models. RESULTS: Individuals with the highest concentrations of C-peptide were more likely to have adenomas (OR = 2.2, 95% CI 1.4-4.0) than those with the lowest concentrations; associations that appeared to be stronger in men (OR = 4.4, 95% CI 1.7-10.9) than women. Individuals with high insulin concentrations also had a higher risk of adenomas (OR = 3.5, 95% CI 1.7-7.4), whereas higher levels of IGFBP-1 were associated with a reduced risk of adenomas in men only (OR = 0.3, 95% CI 0.1-0.7). Overweight and obese individuals with higher C-peptide levels (>1(st) Q) were at increased risk for lower apoptosis index (OR = 2.5, 95% CI 0.9-7.1), an association that remained strong in overweight and obese men (OR = 6.3, 95% CI 1.0-36.7). Higher levels of IGFBP-1 in overweight and obese individuals were associated with a reduced risk of low apoptosis (OR = 0.3, 95% CI 0.1-1.0). CONCLUSIONS: Associations between these peptides and the apoptosis index in overweight and obese individuals, suggest that the mechanism by which C-peptide could induce adenomas may include its anti-apoptotic properties. This study suggests that hyperinsulinemia and IGF hormones predict adenoma risk, and that outcomes associated with colorectal carcinogenesis maybe modified by gender.


Assuntos
Adenoma/metabolismo , Peptídeo C/metabolismo , Neoplasias Colorretais/metabolismo , Insulina/metabolismo , Mucosa Intestinal/metabolismo , Adulto , Idoso , Apoptose , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Risco
16.
Cancer Causes Control ; 23(7): 1127-38, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22565227

RESUMO

PURPOSE: Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. METHODS: Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression. RESULTS: The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05). CONCLUSIONS: These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.


Assuntos
Adiponectina/genética , Neoplasias do Colo/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like I/genética , Polimorfismo Genético , Adiponectina/metabolismo , Negro ou Afro-Americano/genética , Idoso , Peptídeo C/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Técnicas de Genotipagem/métodos , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Branca/genética
17.
BMC Cancer ; 8: 143, 2008 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-18498652

RESUMO

BACKGROUND: IGF binding protein-3 (IGFBP-3) regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties. Elevated plasma IGFBP-3 has been associated with reduced risk of colorectal cancer (CRC), but the role of tissue IGFBP-3 is not well defined. We evaluated the association between tissue or plasma IGFBP-3 and risk of colorectal adenomas or low apoptosis. METHODS: Subjects were consenting patients who underwent a clinically indicated colonoscopy at UNC Hospitals and provided information on diet and lifestyle. IGFBP-3 mRNA in normal colon was assessed by real time RT-PCR. Plasma IGFBP-3 was measured by ELISA and apoptosis was determined by morphology on H & E slides. Logistic regression was used to compute odds ratio (OR) and 95% confidence intervals. RESULTS: We observed a modest correlation between plasma IGFBP-3 and tissue IGFBP-3 expression (p = 0.007). There was no significant association between plasma IGFBP-3 and adenomas or apoptosis. Tissue IGFBP-3 mRNA expression was significantly lower in cases than controls. Subjects in the lowest three quartiles of tissue IGFBP-3 gene expression were more likely to have adenomas. Consistent with previous reports, low apoptosis was significantly associated with increased risk of adenomas (p = 0.003). Surprisingly, local IGFBP-3 mRNA expression was inversely associated with apoptosis. CONCLUSION: Low expression of IGFBP-3 mRNA in normal colonic mucosa predicts increased risk of adenomas. Our findings suggest that local IGFBP-3 in the colon may directly increase adenoma risk but IGFBP-3 may act through a pathway other than apoptosis to influence adenoma risk.


Assuntos
Adenoma/metabolismo , Apoptose , Neoplasias Colorretais/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Adenoma/patologia , Adenoma/prevenção & controle , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Masculino , Mucosa/metabolismo , Mucosa/patologia , Razão de Chances , Valor Preditivo dos Testes , RNA Mensageiro/análise , Fatores de Risco , Estatística como Assunto , Estados Unidos
18.
Clin Gastroenterol Hepatol ; 4(9): 1103-11, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16820326

RESUMO

BACKGROUND & AIMS: Inflammatory cytokine polymorphisms are associated with gastric adenocarcinoma in Helicobacter pylori-infected patients in Europe and Asia. We investigated the cytokine profile in the Latino population, specifically Honduras, a high-incidence region, and the use of the combination prevalence of H pylori and genotypes in identifying high-risk populations. METHODS: A population-based case-control study identified 170 incident gastric cancer cases and 162 healthy village controls. Interleukin (IL)-Ibeta-511, IL-1RN, IL-10-1082, and tumor necrosis factor-alpha-308 genotypes were determined. We define the combination prevalence index (CPI) as the product of H pylori and IL-1beta-511T+ genotype prevalence in healthy subjects. Medline identified gastric cancer studies to facilitate country-specific CPI calculations. RESULTS: In healthy, population-based Honduran controls, IL-1beta-511T+ prevalence was 81% (95% confidence interval, 75%-87%; CT, 57%; TT, 25%), which was among the highest reported. IL-10-1082A+ prevalence was 93% (95% confidence interval, 88%-97%), mirroring Asian populations. Seventeen percent were homozygous for both proinflammatory cytokines (TT/AA), with increased risk among cases (odds ratio, 2.6; 95% confidence intervals, 1.0-6.8). Tumor necrosis factor-alpha polymorphisms were nearly absent. Endemic H pylori infection (85%) was confirmed. Importantly, the CPI association with country incidence is highly significant (P = .0057), based on 16 global populations and Honduras. Sensitivity analysis confirms a robust CPI. CONCLUSIONS: The CPI, based on IL-1beta genotypes, has a strong association with country-specific gastric cancer incidence. The CPI correlation supports the chronic inflammation carcinogenesis model, and may explain the geographic variation. We report a novel cytokine profile in Honduras that mirrors Asian populations and explains the high incidence rates. This may have dyspepsia management and screening implications for the growing US Latino population.


Assuntos
Citocinas/genética , Infecções por Helicobacter/etnologia , Helicobacter pylori , Polimorfismo Genético , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Genótipo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Honduras/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Neoplasias Gástricas/complicações
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