Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brai...Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brain neoplasms. Meth- ods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms. The results of the measurements with different slice thickness were compared. Calculation of coefficient of variation (CV), and relative paired difference of the measurements were used to determine the levels of inter- and intraobserver reproducibility. Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant (P < 0.05) respectively in observer 2, and were not significant in the other two observers (P > 0.05). For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant. Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group. Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group. The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively. No other intraobserver differences of measurements were statistically significant. CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers. Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness. Suitable training may be helpful to maintain a high level of consistency for measurements.展开更多
AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer ...AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010.Data analyzed consisted of demographic and clinical variables.The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test.RESULTS:One hundred and forty two patients were reviewed.Median age was 64 years(36-86 years).Eighty eight patients(62%) received neoadjuvant chemoradiotherapy.Pathological complete and partial responses were achieved in 17(19%) and 71(81%) patients.Cancer relapsed in 43/142(30%) patients.The brain was the first site of relapse in 9/43 patients(21%,95% CI:10%-36%).HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9(56%) cases overexpressed HER-2(3+ staining).CONCLUSION:HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy.Further studies will be required to validate this observation.展开更多
AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, t...AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n=0, stomach: n=10, colorectal: n=47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray (Gy) or 3Gy to a total dose of 50Gy or 30Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6mo vs 8.0mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n=916) was 3.4mo and 3.2mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n=57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70 was 5.5mo vs 2.1mo for patients with KPS <70 (P<0.01, log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.展开更多
Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. It is more common in far eastern countries and relatively rare in the United States and western European countries where at autopsy...Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. It is more common in far eastern countries and relatively rare in the United States and western European countries where at autopsy it accounts for only 1-2% of malignant rumors, The disease is usually manifested in the the 6^th and 7^th decade of life. HCC is one of the highly malignant neoplasms, Extrahepatic metastases are seen in 64% of patients with HCC. The lungs, regional lymph nodes, kidney, bone marrow and adrenals are common sites of HCC metastasis^[1-3], But, metastasis to brain and skull is extremely rare. Table I shows some of the reported cases of HCC with brain metastasis. These case reports reaffirms the complex and multidisciplinary care of these patients^[4-5].展开更多
Objective The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer.
BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutatio...BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutation,which is associated with metastasis and poorer survival.However,the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear.AIM To evaluate the clinicopathological characteristics and prognostic value of codonspecific KRAS mutations,especially in codon 13.METHODS This retrospective,single-center,observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019.Patients with KRAS mutation status confirmed by molecular pathology reports were included.The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed.Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.RESULTS Among the 2203 patients,the incidence of KRAS codons 12,13,and 61 mutations was 27.7%,9.1%,and 1.3%,respectively.Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics,but only codon 12 was associated with pathological features,such as stage of primary tumor(T stage),lymph node involvement(N stage),vascular invasion,perineural invasion,tumor size,and microsatellite instability.KRAS codon 13 mutation showed no associations(77.2%vs 85.3%,P=0.159),whereas codon 12 was associated with a lower 5-year recurrence-free survival rate(78.9%vs 75.5%,P=0.025).In multivariable analysis,along with T and N stages and vascular and perineural invasion,only codon 12(hazard ratio:1.399;95%confidence interval:1.034-1.894;P=0.030)among KRAS mutations was an independent risk factor for recurrence.CONCLUSION This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.展开更多
Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individ...Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individual fractional anisotropy values with N-acetylaspartate/creatine and N-acetylaspartate/choline ratios in tumors, edema, and normal white matter. This study divided the brain parenchyma into tumor, pedtumoral edema, and normal-appearing white matter according to MRI data, and analyzed the correlation of metabolites with water molecular diffusion. Results demonstrated that in normal-appearing white matter, N-acetylaspartate/creatine ratios were positively correlated with fractional anisotropy values, negatively correlated with radial diffusivities, and positively correlated with maximum eigenvalues. Maximum eigenvalues and radial diffusivities in peritumoral edema showed a negative correlation with choline, N-acetylaspartate, and creatine. Radial diffusivities in tumor demonstrated a negative correlation with choline. These data suggest that the relationship between metabolism and structure is markedly changed from normal white matter to peritumoral edema and tumor. Neural metabolism in the peritumoral edema area decreased with expanding extracellular space. The normal relationship of neural function and microstructure disappeared in the tumor region.展开更多
Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial cons...Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial consequences. Methods: A total of 157 parents completed a questionnaire on the degree of information provision to their children and sociodemographic and medical characteristics. Parents and their children completed subscales of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Relevant factors were investigated using ordinal logistic regression analysis and compared with PedsQL scores by degree of information provision with adjustment for age. Results: The majority of children aged 2 - 4 years received a low level of information only in regard to medical procedure and preparation. The majority of children aged 5 - 11 years were provided information regarding disease symptoms and treatment, but not actual diagnosis. Approximately half of children aged 12 - 18 years were provided detailed information including their actual diagnosis. Older children generally received more information regarding their disease (odds ratio [OR] = 1.3 per 1 year old, P < 0.001), while children with intellectual disability received less (OR = 0.2, P = 0.006). The provision of information did not worsen scores for Procedural Anxiety, Treatment Anxiety, Worry, or Communication. Conclusions: To our knowledge, this is the first report on the degree of information provision to children with brain tumors. Parents of children with brain tumors in Japan provide information dependent on age and intellectual level. The disclosure of information to children regarding their disease might affect their trust of medical and health care professionals.展开更多
Objective： To investigate the expression of IL-13Ra2 gene in brain tumors. Methods： Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expre...Objective： To investigate the expression of IL-13Ra2 gene in brain tumors. Methods： Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expression was evaluated by reverse transcriptase polymerase chain reaction and immunohistochemical analysis. Results： IL-13Ra2 gene was highly expressed in glioblastoma, medulloblastoma, malignant meningioma and benign meningioma. Conclusion： Human IL-13Ra2 gene is expressed in brain tumors in addition to gliomas, and our result indicates that the IL-13Ra2 gene promoter based gene therapy method can be used to treat brain tumors in addition to gliomas. Further studies involving larger numbers of samples are necessary to fully understand the expression profile of IL-13Ra2 gene in the brain tumors.展开更多
Objective： To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Methods： Rabbit VX2 brain tumor model was ...Objective： To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Methods： Rabbit VX2 brain tumor model was established by injection of 100 μL viable tumor cells （10qmL） through a 2 mm-hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by dental drill. MRI was performed every 2 days after seven days of implantation to evaluate the growth of the tumor. Twenty New Zealand White rabbits with tumor size over 3 mm in diameter were randomly divided into 2 groups according to the tumor growth time with those less than 3 weeks as group 1 and those more than 3 weeks as group 2, and perfusion CT were performed accordingly. CT measurements of BV, BF and PS from tumor, peritumor and contralateral normal tissue regions were obtained. After that the animals were sacrificed and 2% Evans blue （2 mL/kg） was given intravenously in 16 of these animals 1 h prior to sacrifice to detect breakdown of the blood brain barrier. VEGF and MVD were evaluated in immunohistochemical examination of the specimens. Results： Tumor had significantly higher BV, BF and PS （P=0.000） than peritumor and normal tissue region. Tumor BV, BF and MVD in group 2 were significantly higher than that in group 1 （P〈0.01）. Significant linear correlation was found between MVD and BV （t=-0.915, P=-0.000）, MVD and BF （t=0.901, P=-0.000）, and MVD and PS （t=-0.459, P=0.042）. We also found a rank correlation between PS and blue stain of tumor （rs=0.861, P=0.000）. Conclusion： Perfusion CT can distinguish tumor from peritumor and normal tissue clearly, reflect tumor angiogenesis accurately, and provide useful information for the evaluation of brain tumor.展开更多
Langerhans cell histiocytosis(LCH)is a rare proliferative histiocyte disorder.It can affect any organ or system,especially the bone,skin,lung,and central nervous system(CNS).In the CNS,the hypothalamic-pituitary is pr...Langerhans cell histiocytosis(LCH)is a rare proliferative histiocyte disorder.It can affect any organ or system,especially the bone,skin,lung,and central nervous system(CNS).In the CNS,the hypothalamic-pituitary is predominantly affected,whereas the brain parenchyma is rarely affected.LCH occurring in the brain parenchyma can be easily confused with glioblastoma or brain metastases.Thus,multimodal imaging is useful for the differential diagnosis of these intracerebral lesions and detection of lesions in the other organs.CASE SUMMARY A 47-year-old man presented with a headache for one week and sudden syncope.Brain computed tomography(CT)and magnetic resonance imaging showed an irregularly shaped nodule with heterogeneous enhancement.On^(18)F-fluorodeoxyglucose(^(18)F-FDG)positron emission tomography/CT,a nodule with^(18)F-FDG uptake and multiple cysts in the upper lobes of both lungs were noted,which was also confirmed by high-resolution CT.Thus,the patient underwent surgical resection of the brain lesion for further examination.Postoperative pathology confirmed LCH.The patient received chemotherapy after surgery.No recurrence was observed in the brain at the 12-mo follow-up.CONCLUSION Multimodal imaging is useful for evaluating the systemic condition of LCH,developing treatment plans,and designing post-treatment strategies.展开更多
To assess the clinical value of treatment with 131I for brain metastases from differentiated thyroid cancer (DTC), we have observed 8 cases of brain metastases from DTC who received follow-up after 131I therapy (2male...To assess the clinical value of treatment with 131I for brain metastases from differentiated thyroid cancer (DTC), we have observed 8 cases of brain metastases from DTC who received follow-up after 131I therapy (2male, 6 female, aged 12～65 years). The results of 131I therapy were evaluated with clinical presentation, imaging scan and survival analysis. The main results are as follows. (1) All cases had been survival for 2～35 years in follow-up. (2)A space-occupying lesion in right cerebellum was reduced after taking 20.65 GBq and disappeared after 23.61 GBq,demonstrated by computed tomography. (3) The sequences and doses of 131I therapy were clearly decreased for the cases with total thyroidectomy in comparison with those with semithyroidectomy (p＜0.01). (4) The brain metastases with lung and/or bone metastasis from DTC were 75% (6/8) and it was difficult to cure these metastases at the same time. It is concluded that the postoperative treatment of 131I for brain metastases from DTC after undergoing thyroidectomy may improve clinical symptoms and life quality, reduce lesions, and prolong survival.展开更多
Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory ...Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR.S6K1 and4E-BP1 are important downstream effectors of mTORC1.In this study,we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1in the protection of retinal ganglion cells.We transfected an optic nerve crush mouse model with adeno-associated viral 2-mediated constitutively active Rheb and observed the effects on retinal ganglion cell survival and axon regeneration.We found that overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute(14 days) and chronic(21 and 42 days) stages of injury.We also found that either co-expression of the dominant-negative S6K1mutant or the constitutively active 4E-BP1 mutant together with constitutively active Rheb markedly inhibited axon regeneration of retinal ganglion cells.This suggests that mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.However,only S6K1 activation,but not 4E-BP1 knockdown,induced axon regeneration when applied alone.Furthermore,S6K1 activation promoted the survival of retinal ganglion cells at 14 days post-injury,whereas 4E-BP1 knockdown unexpectedly slightly decreased the survival of retinal ganglion cells at 14 days postinjury.Ove rexpression of constitutively active 4E-BP1 increased the survival of retinal ganglion cells at 14 days post-injury.Likewise,co-expressing constitutively active Rheb and constitutively active 4E-BP1 markedly increased the survival of retinal ganglion cells compared with overexpression of constitutively active Rheb alone at 14 days post-injury.These findings indicate that functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rhe b/mTOR.Together,our results show that constitutively active Rheb promotes the survival of retinal ganglion cells and axon regeneration through modulating S6K1 and 4E-BP1 activity.Phosphorylated S6K1 and 4E-BP1 promote axon regeneration but play an antagonistic role in the survival of retinal ganglion cells.展开更多
文摘Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brain neoplasms. Meth- ods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms. The results of the measurements with different slice thickness were compared. Calculation of coefficient of variation (CV), and relative paired difference of the measurements were used to determine the levels of inter- and intraobserver reproducibility. Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant (P < 0.05) respectively in observer 2, and were not significant in the other two observers (P > 0.05). For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant. Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group. Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group. The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively. No other intraobserver differences of measurements were statistically significant. CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers. Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness. Suitable training may be helpful to maintain a high level of consistency for measurements.
基金Supported by The Iowa Leukemia and Cancer Research Fund at University of Iowa Hospitals and clinics
文摘AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010.Data analyzed consisted of demographic and clinical variables.The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test.RESULTS:One hundred and forty two patients were reviewed.Median age was 64 years(36-86 years).Eighty eight patients(62%) received neoadjuvant chemoradiotherapy.Pathological complete and partial responses were achieved in 17(19%) and 71(81%) patients.Cancer relapsed in 43/142(30%) patients.The brain was the first site of relapse in 9/43 patients(21%,95% CI:10%-36%).HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9(56%) cases overexpressed HER-2(3+ staining).CONCLUSION:HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy.Further studies will be required to validate this observation.
文摘AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n=0, stomach: n=10, colorectal: n=47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray (Gy) or 3Gy to a total dose of 50Gy or 30Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6mo vs 8.0mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n=916) was 3.4mo and 3.2mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n=57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70 was 5.5mo vs 2.1mo for patients with KPS <70 (P<0.01, log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.
文摘Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. It is more common in far eastern countries and relatively rare in the United States and western European countries where at autopsy it accounts for only 1-2% of malignant rumors, The disease is usually manifested in the the 6^th and 7^th decade of life. HCC is one of the highly malignant neoplasms, Extrahepatic metastases are seen in 64% of patients with HCC. The lungs, regional lymph nodes, kidney, bone marrow and adrenals are common sites of HCC metastasis^[1-3], But, metastasis to brain and skull is extremely rare. Table I shows some of the reported cases of HCC with brain metastasis. These case reports reaffirms the complex and multidisciplinary care of these patients^[4-5].
文摘Objective The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer.
文摘BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutation,which is associated with metastasis and poorer survival.However,the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear.AIM To evaluate the clinicopathological characteristics and prognostic value of codonspecific KRAS mutations,especially in codon 13.METHODS This retrospective,single-center,observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019.Patients with KRAS mutation status confirmed by molecular pathology reports were included.The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed.Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.RESULTS Among the 2203 patients,the incidence of KRAS codons 12,13,and 61 mutations was 27.7%,9.1%,and 1.3%,respectively.Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics,but only codon 12 was associated with pathological features,such as stage of primary tumor(T stage),lymph node involvement(N stage),vascular invasion,perineural invasion,tumor size,and microsatellite instability.KRAS codon 13 mutation showed no associations(77.2%vs 85.3%,P=0.159),whereas codon 12 was associated with a lower 5-year recurrence-free survival rate(78.9%vs 75.5%,P=0.025).In multivariable analysis,along with T and N stages and vascular and perineural invasion,only codon 12(hazard ratio:1.399;95%confidence interval:1.034-1.894;P=0.030)among KRAS mutations was an independent risk factor for recurrence.CONCLUSION This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.
基金supported by the National Natural Science Foundation of China, No. 81171318Shaanxi Provincial Scientific Research Project, No. 2012K13-02-24
文摘Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individual fractional anisotropy values with N-acetylaspartate/creatine and N-acetylaspartate/choline ratios in tumors, edema, and normal white matter. This study divided the brain parenchyma into tumor, pedtumoral edema, and normal-appearing white matter according to MRI data, and analyzed the correlation of metabolites with water molecular diffusion. Results demonstrated that in normal-appearing white matter, N-acetylaspartate/creatine ratios were positively correlated with fractional anisotropy values, negatively correlated with radial diffusivities, and positively correlated with maximum eigenvalues. Maximum eigenvalues and radial diffusivities in peritumoral edema showed a negative correlation with choline, N-acetylaspartate, and creatine. Radial diffusivities in tumor demonstrated a negative correlation with choline. These data suggest that the relationship between metabolism and structure is markedly changed from normal white matter to peritumoral edema and tumor. Neural metabolism in the peritumoral edema area decreased with expanding extracellular space. The normal relationship of neural function and microstructure disappeared in the tumor region.
文摘Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial consequences. Methods: A total of 157 parents completed a questionnaire on the degree of information provision to their children and sociodemographic and medical characteristics. Parents and their children completed subscales of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Relevant factors were investigated using ordinal logistic regression analysis and compared with PedsQL scores by degree of information provision with adjustment for age. Results: The majority of children aged 2 - 4 years received a low level of information only in regard to medical procedure and preparation. The majority of children aged 5 - 11 years were provided information regarding disease symptoms and treatment, but not actual diagnosis. Approximately half of children aged 12 - 18 years were provided detailed information including their actual diagnosis. Older children generally received more information regarding their disease (odds ratio [OR] = 1.3 per 1 year old, P < 0.001), while children with intellectual disability received less (OR = 0.2, P = 0.006). The provision of information did not worsen scores for Procedural Anxiety, Treatment Anxiety, Worry, or Communication. Conclusions: To our knowledge, this is the first report on the degree of information provision to children with brain tumors. Parents of children with brain tumors in Japan provide information dependent on age and intellectual level. The disclosure of information to children regarding their disease might affect their trust of medical and health care professionals.
基金This work was supported by National Natural Science Foundation of China (No.303000100) and HYD Educational Foundation (No. 94018).
文摘Objective： To investigate the expression of IL-13Ra2 gene in brain tumors. Methods： Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expression was evaluated by reverse transcriptase polymerase chain reaction and immunohistochemical analysis. Results： IL-13Ra2 gene was highly expressed in glioblastoma, medulloblastoma, malignant meningioma and benign meningioma. Conclusion： Human IL-13Ra2 gene is expressed in brain tumors in addition to gliomas, and our result indicates that the IL-13Ra2 gene promoter based gene therapy method can be used to treat brain tumors in addition to gliomas. Further studies involving larger numbers of samples are necessary to fully understand the expression profile of IL-13Ra2 gene in the brain tumors.
文摘Objective： To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Methods： Rabbit VX2 brain tumor model was established by injection of 100 μL viable tumor cells （10qmL） through a 2 mm-hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by dental drill. MRI was performed every 2 days after seven days of implantation to evaluate the growth of the tumor. Twenty New Zealand White rabbits with tumor size over 3 mm in diameter were randomly divided into 2 groups according to the tumor growth time with those less than 3 weeks as group 1 and those more than 3 weeks as group 2, and perfusion CT were performed accordingly. CT measurements of BV, BF and PS from tumor, peritumor and contralateral normal tissue regions were obtained. After that the animals were sacrificed and 2% Evans blue （2 mL/kg） was given intravenously in 16 of these animals 1 h prior to sacrifice to detect breakdown of the blood brain barrier. VEGF and MVD were evaluated in immunohistochemical examination of the specimens. Results： Tumor had significantly higher BV, BF and PS （P=0.000） than peritumor and normal tissue region. Tumor BV, BF and MVD in group 2 were significantly higher than that in group 1 （P〈0.01）. Significant linear correlation was found between MVD and BV （t=-0.915, P=-0.000）, MVD and BF （t=0.901, P=-0.000）, and MVD and PS （t=-0.459, P=0.042）. We also found a rank correlation between PS and blue stain of tumor （rs=0.861, P=0.000）. Conclusion： Perfusion CT can distinguish tumor from peritumor and normal tissue clearly, reflect tumor angiogenesis accurately, and provide useful information for the evaluation of brain tumor.
基金Supported by Guangdong Medical Research Fund to Han-Xiang Liang,No.B2021084Traditional Chinese Medicine Bureau of Guangdong Province to En-Tao Liu,No.20211005High-level Hospital Construction Research Project of Maoming People's Hospital to Han-Xiang Liang,No.ZX2020014.
文摘Langerhans cell histiocytosis(LCH)is a rare proliferative histiocyte disorder.It can affect any organ or system,especially the bone,skin,lung,and central nervous system(CNS).In the CNS,the hypothalamic-pituitary is predominantly affected,whereas the brain parenchyma is rarely affected.LCH occurring in the brain parenchyma can be easily confused with glioblastoma or brain metastases.Thus,multimodal imaging is useful for the differential diagnosis of these intracerebral lesions and detection of lesions in the other organs.CASE SUMMARY A 47-year-old man presented with a headache for one week and sudden syncope.Brain computed tomography(CT)and magnetic resonance imaging showed an irregularly shaped nodule with heterogeneous enhancement.On^(18)F-fluorodeoxyglucose(^(18)F-FDG)positron emission tomography/CT,a nodule with^(18)F-FDG uptake and multiple cysts in the upper lobes of both lungs were noted,which was also confirmed by high-resolution CT.Thus,the patient underwent surgical resection of the brain lesion for further examination.Postoperative pathology confirmed LCH.The patient received chemotherapy after surgery.No recurrence was observed in the brain at the 12-mo follow-up.CONCLUSION Multimodal imaging is useful for evaluating the systemic condition of LCH,developing treatment plans,and designing post-treatment strategies.
文摘To assess the clinical value of treatment with 131I for brain metastases from differentiated thyroid cancer (DTC), we have observed 8 cases of brain metastases from DTC who received follow-up after 131I therapy (2male, 6 female, aged 12～65 years). The results of 131I therapy were evaluated with clinical presentation, imaging scan and survival analysis. The main results are as follows. (1) All cases had been survival for 2～35 years in follow-up. (2)A space-occupying lesion in right cerebellum was reduced after taking 20.65 GBq and disappeared after 23.61 GBq,demonstrated by computed tomography. (3) The sequences and doses of 131I therapy were clearly decreased for the cases with total thyroidectomy in comparison with those with semithyroidectomy (p＜0.01). (4) The brain metastases with lung and/or bone metastasis from DTC were 75% (6/8) and it was difficult to cure these metastases at the same time. It is concluded that the postoperative treatment of 131I for brain metastases from DTC after undergoing thyroidectomy may improve clinical symptoms and life quality, reduce lesions, and prolong survival.
基金National Natural Science Foundation of China,Nos.82070967,81770930the Natural Science Foundation of Hunan Province,No.2020jj4788 (all to BJ)。
文摘Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR.S6K1 and4E-BP1 are important downstream effectors of mTORC1.In this study,we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1in the protection of retinal ganglion cells.We transfected an optic nerve crush mouse model with adeno-associated viral 2-mediated constitutively active Rheb and observed the effects on retinal ganglion cell survival and axon regeneration.We found that overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute(14 days) and chronic(21 and 42 days) stages of injury.We also found that either co-expression of the dominant-negative S6K1mutant or the constitutively active 4E-BP1 mutant together with constitutively active Rheb markedly inhibited axon regeneration of retinal ganglion cells.This suggests that mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.However,only S6K1 activation,but not 4E-BP1 knockdown,induced axon regeneration when applied alone.Furthermore,S6K1 activation promoted the survival of retinal ganglion cells at 14 days post-injury,whereas 4E-BP1 knockdown unexpectedly slightly decreased the survival of retinal ganglion cells at 14 days postinjury.Ove rexpression of constitutively active 4E-BP1 increased the survival of retinal ganglion cells at 14 days post-injury.Likewise,co-expressing constitutively active Rheb and constitutively active 4E-BP1 markedly increased the survival of retinal ganglion cells compared with overexpression of constitutively active Rheb alone at 14 days post-injury.These findings indicate that functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rhe b/mTOR.Together,our results show that constitutively active Rheb promotes the survival of retinal ganglion cells and axon regeneration through modulating S6K1 and 4E-BP1 activity.Phosphorylated S6K1 and 4E-BP1 promote axon regeneration but play an antagonistic role in the survival of retinal ganglion cells.
