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1.
Br J Cancer ; 121(12): 991-1000, 2019 12.
Article in English | MEDLINE | ID: mdl-31719684

ABSTRACT

BACKGROUND: Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses. METHODS: The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient's prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan-Meier method). RESULTS: CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2-/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR- (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8-92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5-17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18-3.75, triple-negative and HER2-/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2-8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50-0.64) for HER2+/HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65-0.81) for HER2+/HR-, 4.4 months (HR = 1.55, 95% CI: 1.42-1.69) for triple-negative and 7.1 months for HER2-/HR+ patients (p <0.0001). CONCLUSIONS: Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients. CLINICAL TRIAL REGISTRATION: NCT03275311.


Subject(s)
Breast Neoplasms, Male/epidemiology , Nervous System Neoplasms/epidemiology , Triple Negative Breast Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Breast Neoplasms, Male/classification , Breast Neoplasms, Male/genetics , Breast Neoplasms, Male/pathology , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Kinetics , Male , Middle Aged , Neoplasm Metastasis , Nervous System Neoplasms/genetics , Nervous System Neoplasms/pathology , Nervous System Neoplasms/secondary , Prognosis , Receptor, ErbB-2/genetics , Triple Negative Breast Neoplasms/classification , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Young Adult
3.
Zhongguo Fei Ai Za Zhi ; 19(5): 252-6, 2016 May 20.
Article in Chinese | MEDLINE | ID: mdl-27215452

ABSTRACT

BACKGROUND: Leptomeningeal carcinomatosis is a rare type of metastatic tumors of the central nervous system. In recent years, with the improvement of neoplasms therapies and longer survival of patients by better systemic control, incidence of leptomeningeal metastases has increased every year. However, there is still lack of effective therapies. The aim of this study is to investigate the efficacy, security and prognosis of intrathecal chemotherapy with methotrexate (MTX) in the treatment of neoplastic meningitis. METHODS: A total of 27 patients were enrolled. We investigated clinical features and cerebrospinal fluid (CSF) examination results retrospectively, and analyzed the adverse reactions as well as prognosis after intrathecal chemotherapy. RESULTS: All 27 patients were treated by intrathecal MTX, 70.4% had clinical remission, however, there was no significant difference in CSF pressure and CSF biochemical changes. We observed that 55.6% patients were all appropriate, 25.9% appeared lower limb numbness and mild pain, no serious irreversible adverse reactions occurred. Median overall survival was 4 months. CONCLUSIONS: We suggest that intrathecal administration of MTX is associated with improvement of symptoms of leptomeningeal metastasis patients and no severe adverse events observed.


Subject(s)
Meningeal Carcinomatosis/drug therapy , Methotrexate/administration & dosage , Nervous System Neoplasms/drug therapy , Adult , Aged , Female , Humans , Injections, Spinal , Lung Neoplasms/pathology , Male , Meningeal Carcinomatosis/secondary , Middle Aged , Neoplasm Metastasis , Nervous System Neoplasms/secondary , Retrospective Studies , Treatment Outcome
4.
Clin Nucl Med ; 41(6): e301-3, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26825200

ABSTRACT

Brain MRI in an 82-year-old man with presumed Bell's palsy revealed a clinically unsuspected right parotid gland mass but no other acute findings. Biopsy revealed poorly differentiated adenocarcinoma. Staging F-FDG PET/CT revealed an FDG-avid parotid mass, abnormal FDG uptake along the course of the facial nerve from mass to skull base, and multiple FDG-avid right level II neck lymph nodes and hepatic metastases. The PET/CT findings and prolonged clinical course suggest that diffuse perineural spread of tumor from a smoldering parotid neoplasm, and not idiopathic Bell's palsy, was responsible for the patient's facial paralysis.


Subject(s)
Adenocarcinoma/pathology , Facial Paralysis/complications , Facial Paralysis/diagnostic imaging , Nervous System Neoplasms/complications , Nervous System Neoplasms/secondary , Parotid Neoplasms/pathology , Positron Emission Tomography Computed Tomography , Aged, 80 and over , Humans , Male , Parotid Gland/innervation
5.
Cancer J ; 18(5): 463-8, 2012.
Article in English | MEDLINE | ID: mdl-23006953

ABSTRACT

Invasion of cranial nerves and peripheral nerve roots, plexus, or nerves by non-Hodgkin lymphoma is denoted as neurolymphomatosis (NL). Four clinical patterns are recognized. Most commonly, NL presents as a painful polyneuropathy or polyradiculopathy, followed by cranial neuropathy, painless polyneuropathy, and peripheral mononeuropathy. Diagnosis of NL is challenging and requires integration of clinical information, imaging findings, and histopathologic examination of involved nerves or nonneural tissue and cerebrospinal fluid analysis. In the rare cases of primary NL, the diagnosis is often delayed. Successful therapy is contingent upon recognition of the disease and its exact neuroanatomic localization without delay. Treatment options include systemic chemotherapy and localized irradiation of bulky disease sites. Concomitant involvement of cerebrospinal fluid and systemic disease sites requires more complex regimens.


Subject(s)
Cranial Nerves/pathology , Lymphoma, Non-Hodgkin/pathology , Nervous System Neoplasms/secondary , Peripheral Nerves/pathology , Polyneuropathies/physiopathology , B-Lymphocytes/pathology , Diagnosis, Differential , Humans , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/physiopathology , Lymphoma, Non-Hodgkin/therapy , Neoplasm Invasiveness , Nervous System Neoplasms/diagnosis , Nervous System Neoplasms/therapy , Polyneuropathies/diagnosis , Polyneuropathies/therapy , Polyradiculopathy/diagnosis , Polyradiculopathy/pathology , Polyradiculopathy/physiopathology , Polyradiculopathy/therapy
6.
Oncol Rep ; 28(5): 1531-6, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22895597

ABSTRACT

We have previously classified wall invasion patterns of gallbladder carcinoma (GBC) cases into two groups, i.e., the infiltrative growth type (IG type) and destructive growth type (DG type). The DG type was significantly associated with poor differentiation, aggressive infiltration and decreased postoperative survival in terms of its histological differentiation, lymphatic invasion, venous invasion, lymph node status, neural invasion and mode of subserosal infiltration. In the present study, we analyzed 42 surgically-resected subserosal invasive gallbladder adenocarcinomas, invading the perimuscular connective tissue (pT2). The cumulative 5-year survival rate in the series was 48.7%. Lymphatic invasion (p=0.021), venous invasion (p=0.020), mode of subserosal infiltration (p<0.001), histological differentiation (p=0.030) and biliary infiltration (p=0.007) were noted, respectively, at a significantly higher incidence in more aggressive infiltration or poor differentiation in the DG type. The cumulative 5-year survival rate of curative resection cases was lower in patients with the DG type than in those with the IG type (68.9 versus 20.2%, respectively, p=0.006, log-rank test). On Cox's proportional hazard regression modeling, the low degree of venous/perineural invasion and IG type of wall invasion pattern were associated with a significant improvement in overall survival. Our data suggest that the wall invasion pattern is an independent predictor of survival in subserosal invasive GBC. Regarding the clinical application of our concept, on the classification of patients with subserosal invasive GBC based on a combination of the wall invasion pattern and lymph node status, the overall survival rate in patients with the DG type and/or N2 metastasis (n=21) was lower than in patients with the IG type and N0, 1 metastasis (n=21) (p=0.0023, log-rank test). The wall invasion pattern could contribute to decision-making concerning curative resection for subserosal invasive GBC.


Subject(s)
Gallbladder Neoplasms/pathology , Gallbladder/pathology , Lymphatic Metastasis , Nervous System Neoplasms/secondary , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Cell Proliferation , Female , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/surgery , Humans , Ki-67 Antigen/analysis , Male , Middle Aged , Neoplasm Invasiveness , Prognosis
8.
Expert Rev Anticancer Ther ; 12(3): 359-71, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22369327

ABSTRACT

Perineural involvement is a well-recognized clinicopathologic entity found in head and neck (H&N) cancers, including mucosal epithelial carcinomas and salivary gland malignancies. Perineural disease remains a diagnostic, prognostic and therapeutic challenge for the multidisciplinary H&N oncology team. Nerves are important routes of tumor spread in H&N malignancies, yet the biology and prognostic implications of perineural tumor growth are not fully understood. On balance, the available evidence suggests that it is associated with an increased risk of locoregional recurrence but the impact on survival remains uncertain. Perineural involvement has implications for locoregional disease diagnosis and management. MRI is the best imaging modality to detect tumor extent. Advanced radiotherapy technologies such as intensity-modulated radiation therapy and image-guided radiation therapy have the potential for more accurate targeting and treatment of anatomically complex patterns of disease spread. This review is limited to nondermatologic H&N cancers.


Subject(s)
Carcinoma/secondary , Head and Neck Neoplasms , Magnetic Resonance Imaging/methods , Nervous System Neoplasms/secondary , Peripheral Nerves/pathology , Radiotherapy, Image-Guided/methods , Disease Management , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/physiopathology , Head and Neck Neoplasms/radiotherapy , Humans , Mucous Membrane/innervation , Mucous Membrane/pathology , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Paranasal Sinuses/innervation , Paranasal Sinuses/pathology , Stomatognathic System/innervation , Stomatognathic System/pathology , Technology, Radiologic
9.
J Surg Oncol ; 106(2): 169-73, 2012 Aug 01.
Article in English | MEDLINE | ID: mdl-22354558

ABSTRACT

BACKGROUND: In our institution, patients with medullary thyroid carcinoma (MTC) concurrent with nodular goiter (NG) have a nearly 100% survival rate, but the reasons and characteristics are unclear. METHODS: Eighty patients with MTC who underwent surgery in our center between 1971 and 2011 were reviewed. RESULTS: A total of 21 MTC/NG and 59 MTC only patients were identified. The stage of the two groups had no significant difference (P = 0.13). The MTC/NG group had lower preoperative serum calcitonin (CT) levels (914.7 ng/L vs. 1162.6 ng/L, P = 0.003), lower postoperative serum CT levels (371.4 ng/L vs. 582.5 ng/L, P < 0.001), lower carcinoembryonic antigen levels (18.3 ng/ml vs. 130.5 ng/ml, P < 0.001), a lower propensity toward lymph node metastasis (40.0% vs. 66.7%, P = 0.07), and a lower proportion of multifocality (19.1% vs. 42.4%, P = 0.06), capsular invasion (9.5% vs. 25.4%, P = 0.21), and vascular invasion (4.8% vs. 10.1%, P = 0.67). The mean tumor diameter of the two groups was similar (20.3 mm vs. 22.1 mm, P = 0.6). Overall 15-year survival in MTC/NG versus MTC only groups was 100% versus 57.0% (P = 0.03). CONCLUSIONS: MTC with NG is an indolent disease and has an excellent prognosis. The only independent predictor of survival was the TNM stage of disease.


Subject(s)
Carcinoma, Medullary/pathology , Goiter, Nodular/pathology , Thyroid Neoplasms/pathology , Thyroidectomy , Adolescent , Adult , Aged , Analysis of Variance , Biomarkers, Tumor/blood , Calcitonin/blood , Carcinoembryonic Antigen/blood , Carcinoma, Medullary/mortality , Carcinoma, Medullary/surgery , China/epidemiology , Female , Goiter, Nodular/mortality , Goiter, Nodular/surgery , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Nervous System Neoplasms/secondary , Prognosis , Retrospective Studies , Risk Factors , Sample Size , Thyroid Neoplasms/mortality , Thyroid Neoplasms/surgery , Vascular Neoplasms/secondary
10.
Wiad Lek ; 65(2): 97-101, 2012.
Article in Polish | MEDLINE | ID: mdl-23289254

ABSTRACT

INTRODUCTION: Small cell lung cancer (SCLC) includes 10-15% of primary lung tumors and it is very aggressive neoplasm. The aim of this study was to evaluate radiological and clinical features of SCLC and its spread. MATERIAL AND METHODS: The retrospective analysis included 31 patients (18 women, 13 men, mean age: 68.2 +/- 8.34 years).The extensive disease (ED) in most patients was present. 25 patients (80,6%) reported habitual cigarette smoking. Localization of primary tumor, metastases, clinical symptoms and main blood abnormalities were assessed. RESULTS: The most common locations of the primary tumor were: the lung hilus--15 (48.4%), the upper lobe of lung--6 (19.3%) and mediastinum--3 (9.7%). In most cases, mediastinal, subcarinal--both (41.9%) and hilus--(32.2%) lymph nodes were involved. Distant metastases were present in 20 patients (64.5%) at the moment of diagnosis. The most common locations of metastases were: liver--12 (60%), lungs--7 (35%), suprarenal glands--6 (30%), bones--3 (15%) and CNS--3 (15%). The most common symptoms were: cough (77.4%), weakness (51.6%), dyspnea (45.2%), chest pain (41.9%) and the weight loss (30%). Superior vena cava syndrome occurred in 4 patients (13%). The symptoms lasted an average 115 days, but the most persistent were: cough (216 days) and dyspnea (150 days). The main blood tests abnormalities were increased activities of: CRP (mean 63.4 mg/L), AspAT (65U), LDH (1852.7 U/l) and D-dimer (1892.5 microg/l). CONCLUSIONS: SCLC was mainly manifested in CT as central mass lung involving hilus or mediastinum. In most cases, distant metastases were present at the moment of diagnosis.


Subject(s)
Lung Neoplasms/diagnostic imaging , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/secondary , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/secondary , Aged , Aged, 80 and over , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/secondary , Female , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis/diagnostic imaging , Male , Mediastinal Neoplasms/diagnostic imaging , Mediastinal Neoplasms/secondary , Middle Aged , Nervous System Neoplasms/diagnostic imaging , Nervous System Neoplasms/secondary , Retrospective Studies , Tomography, X-Ray Computed
11.
J Natl Cancer Inst ; 102(2): 107-18, 2010 Jan 20.
Article in English | MEDLINE | ID: mdl-20068194

ABSTRACT

BACKGROUND: The ability of cancer to infiltrate along nerves is a common clinical observation in pancreas, head and neck, prostate, breast, and gastrointestinal carcinomas. For these tumors, nerves may provide a conduit for local cancer progression into the central nervous system. Although neural invasion is associated with poor outcome, the mechanism that triggers it is unknown. METHODS: We used an in vitro Matrigel dorsal root ganglion and pancreatic cancer cell coculture model to assess the dynamic interactions between nerves and cancer cell migration and the role of glial cell-derived neurotrophic factor (GDNF). An in vivo murine sciatic nerve model was used to study how nerve invasion affects sciatic nerve function. RESULTS: Nerves induced a polarized neurotrophic migration of cancer cells (PNMCs) along their axons, which was more efficient than in the absence of nerves (migration distance: mean = 187.1 microm, 95% confidence interval [CI] = 148 to 226 microm vs 14.4 microm, 95% CI = 9.58 to 19.22 microm, difference = 143 microm; P < .001; n = 20). PNMC was induced by secretion of GDNF, via phosphorylation of the RET-Ras-mitogen-activated protein kinase pathway. Nerves from mice deficient in GDNF had reduced ability to attract cancer cells (nerve invasion index: wild type vs gdnf+/-, mean = 0.76, 95% CI = 0.75 to 0.77 vs 0.43, 95% CI = 0.42 to 0.44; P < .001; n = 60-66). Tumor specimens excised from patients with neuroinvasive pancreatic carcinoma had higher expression of the GDNF receptors RET and GRFalpha1 as compared with normal tissue. Finally, systemic therapy with pyrazolopyrimidine-1, a tyrosine kinase inhibitor targeting the RET pathway, suppressed nerve invasion toward the spinal cord and prevented paralysis in mice. CONCLUSION: These data provide evidence for paracrine regulation of pancreatic cancer invasion by nerves, which may have important implications for potential therapy directed against nerve invasion by cancer.


Subject(s)
Glial Cell Line-Derived Neurotrophic Factor/metabolism , Nerve Tissue/metabolism , Nervous System Neoplasms/metabolism , Nervous System Neoplasms/secondary , Pancreatic Neoplasms/pathology , Paracrine Communication , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Fluorescent Antibody Technique , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Glial Cell Line-Derived Neurotrophic Factor/genetics , Glial Cell Line-Derived Neurotrophic Factor Receptors/metabolism , Humans , Immunoblotting , Immunohistochemistry , Lentivirus , Male , Mice , Mice, Inbred BALB C , Mitogen-Activated Protein Kinases/metabolism , Neoplasm Invasiveness , Nerve Tissue/pathology , Pancreatic Neoplasms/metabolism , Proto-Oncogene Proteins c-ret/metabolism , RNA Interference , RNA, Small Interfering/metabolism , Sciatic Nerve/metabolism , Sciatic Nerve/pathology , Transduction, Genetic
12.
Arch Esp Urol ; 61(8): 939-43, 2008 Oct.
Article in Spanish | MEDLINE | ID: mdl-19040166

ABSTRACT

OBJECTIVE: Neurological metastases secondary to urological tumors account for 12% overall. The ones derived from germ cells testicular tumors are exceptional in the age of cisplatin. METHODS: We report one case of mixed germ cell tumor in a 49-year-old male patient treated with systemic chemotherapy during 18 months before presenting with severe central and peripheral neurological symptoms leading to death due to massive cerebral hemorrhage. RESULTS: We describe three types of presentation of cerebral metastases in patients with testicular cancer. Type I present synchronically with the primary tumor. Type 2 are diagnosed after a period of remission after conventional cytostatic treatment. Type 3 metastases are diagnosed during the course of the disease and its treatment. CONCLUSIONS: Except unique metastases classified in groups 1 and 2, which are susceptible of surgery or radiosurgery, in which in response may be expected; the rest of lesions secondary to germ cell tumors have an ominous prognosis and outcomes, with short survivals.


Subject(s)
Neoplasms, Germ Cell and Embryonal/secondary , Nervous System Neoplasms/secondary , Testicular Neoplasms/pathology , Fatal Outcome , Humans , Male , Middle Aged
13.
FASEB J ; 22(6): 1839-48, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18234972

ABSTRACT

Many cancers can cause disability and pain by invading nerves. In particular, prostate carcinoma has a high propensity for neural invasion (NI) at an early stage. Attempted surgical treatment of tumors with NI often leads to erectile dysfunction and deteriorated quality of life. Therefore, there is a need for novel modalities that will selectively target cancer cells while preserving neural function. Herpes simplex viruses (HSVs) have a natural trophism for peripheral nerves. We hypothesized that oncolytic therapy using HSV engineered to minimize neurotoxicity would be appropriate for this clinical setting. Attenuated HSV (NV1023) injected to sciatic nerves of nude mice had no toxic effect on nerve function (n=30). NV1023 had significant oncolytic effect on prostate carcinoma cells (PC3, DU145, and LNCap) in vitro. An in vivo model of NI was established by implanting prostate carcinoma cells in the sciatic nerves of nude mice. Mice were treated with NV1023 or saline 7 days after establishment of tumors. Significant reduction in tumor size and inhibition of NI was found 6-8 wk after treatment (P<0.005). All animals treated with saline developed complete paralysis <5 wk post-treatment, whereas most NV1023-treated animals had preserved nerve function >12 wk after treatment (P<0.0001). We conclude that oncolytic therapy effectively treats prostate carcinomas with NI in an in vivo murine model while preserving neural function. These findings may hold significant clinical implications for patients with prostate cancer or other neurotrophic tumors.


Subject(s)
Herpesvirus 1, Human , Nervous System Neoplasms/therapy , Oncolytic Virotherapy/methods , Prostatic Neoplasms/therapy , Vaccines, Attenuated/administration & dosage , Animals , Disease Models, Animal , Herpesvirus 1, Human/genetics , Male , Mice , Mice, Nude , Mutation , Neoplasm Invasiveness , Neoplasms, Experimental , Nervous System Neoplasms/secondary , Oncolytic Virotherapy/adverse effects , Prostatic Neoplasms/pathology , Rats , Sciatic Nerve , Tumor Burden , Vaccines, Attenuated/adverse effects
14.
Cancer Radiother ; 10(3): 107-11, 2006 May.
Article in French | MEDLINE | ID: mdl-16600659

ABSTRACT

PURPOSE: Extra-central nervous system (extra-CNS) metastases are relatively unknown failure patterns in medulloblastoma. The aim of this study was to analyse epidemiological, clinical and aetiopathological aspects of these extra-CNS localisations. PATIENTS AND METHODS: Extra-CNS metastases were retrospectively identified in patients treated in the department of radiation therapy at Salah-Azaïz institute (ISA) for medulloblastoma. These metastases were diagnosed as extra-CNS for all secondary localisations not related to other tumour aetiology. Aetiopathological aspects are discussed with a literature review. RESULTS: Among 103 patients treated and followed-up in the department of radiation therapy of ISA from 1970 to 1992, 8 developed extra-CNS metastases (7.7%). Age at diagnosis of primitive tumour varied from 3 to 23 years. Sex ratio was 1. Primitive tumour treatment was: complete surgical resection in 4 patients with preoperative cerebrospinal fluid shunting in two, cerebrospinal axis irradiation in 7 patients and a cerebral-limited irradiation in 1. Two patients received chemotherapy for their initial treatment (systemic in one case and intrathecal in the other). The mean free-interval from diagnosis of primitive tumour to extra-CNS metastases was 23 months, varying from 8 to 53 months. These metastases were located in the liver (1 case), cervical lymph nodes (2 cases), bone marrow (1 case) and bone (2 cases). Two patients had multiple metastases: bone and bone marrow (in one), lung, pleura, cervical lymph node and bone localisations (in one). Treatment of these metastases was: chemotherapy in 5 cases, chemotherapy and radiation in one, radiation therapy in one and 2 patients were given only supportive care treatment. All patients died or are in progressive disease in less than one year from the diagnosis of extra-CNS metastases. CONCLUSION: Extra-CNS metastases are not rare and have a poor prognosis. The most commonly involved sites are bone, cervical lymph nodes and bone marrow. A complete work-up at initial diagnosis is recommended to screen early metastases. Literature review showed that histopathologic grading might help to identify groups at risk.


Subject(s)
Cerebellar Neoplasms/pathology , Medulloblastoma/secondary , Nervous System Neoplasms/secondary , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Medulloblastoma/diagnosis , Medulloblastoma/therapy , Nervous System Neoplasms/diagnosis , Nervous System Neoplasms/therapy , Retrospective Studies , Risk Factors
15.
Cancer ; 106(6): 1409-17, 2006 Mar 15.
Article in English | MEDLINE | ID: mdl-16475209

ABSTRACT

BACKGROUND: Neuroblastoma (NB) occurs rarely during adolescence, and information is scarce on its characteristics and clinical course in this age group. METHODS: Patients with NB who were included in the Italian Neuroblastoma Registry were considered for the current study. The clinical characteristics and survival of adolescents (age at diagnosis between 10 yrs and 18 yrs) were compared with those of children (ages 1-9 yrs). Infants (age < 1 yr) were excluded because of their well known favorable clinical course. RESULTS: Between 1116 children and 53 adolescents who were evaluated, no differences were documented with regard to the primary tumor site and the prevalence of advanced stage at diagnosis. If only patients with Stage IV NB were considered, then adolescents were less likely to be diagnosed with bone/bone marrow metastases (77%) compared with children (94%; P = 0.038), but adolescents were more likely to have metastases at unusual sites, such as the lung parenchyma or the central nervous system (23% vs. 7%, respectively; P = 0.005). With regard to biologic characteristics, adolescents did not differ significantly from children, although they always had a lower prevalence of unfavorable markers. In particular, MYCN amplification was documented in 21% of children and in 11% of adolescents (P = 0.173). At age 10 years, adolescents had a 20% overall survival rate and a 22% event-free survival rate. Adolescents who had resectable disease had a 73% overall survival rate, which was worse compared with the rate among children with the same disease stage (89%), although the difference did not reach statistical significance (P = 0.159). No differences in survival were observed among patients with Stage IV NB, and adolescents had a probability of survival almost identical to that among children (6% vs. 16%, respectively; P = 0.481). However, when the analysis was restricted to events that occurred after patients developed a recurrence, even if the final outcome was poor for both groups, the difference was statistically significant (P = 0.022) mostly because of the more indolent disease course observed among the adolescents. This effect was even more evident for patients with Stage IV NB. When the 6-year cut-off point was used to separate children from adolescents, a significantly worse overall survival rate (P = 0.036) was documented for adolescents who had resectable disease (81% vs. 93% in children). CONCLUSIONS: NB in adolescents had clinical and biologic characteristics similar to those observed among children. The clinical course of NB probably is correlated significantly with age at diagnosis, but information is scarce on the role of the biologic risk factors in this age group. The authors were able to identify a group of patients with a cut-off age between 6 years and 10 years that had a more indolent course but a worse prognosis.


Subject(s)
Neuroblastoma/diagnosis , Adolescent , Adult , Age Distribution , Bone Neoplasms/diagnosis , Bone Neoplasms/secondary , Bone Neoplasms/therapy , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Infant , Italy , Male , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Nervous System Neoplasms/diagnosis , Nervous System Neoplasms/secondary , Nervous System Neoplasms/therapy , Neuroblastoma/secondary , Neuroblastoma/therapy , Prospective Studies , Retrospective Studies , Survival Rate
16.
Med Wieku Rozwoj ; 9(3 Pt 2): 477-86, 2005.
Article in Polish | MEDLINE | ID: mdl-16719160

ABSTRACT

INTRODUCTION: Neurological origin and multiple localization of neuroblastoma (NB) in children predisposed to the occurrence of neurological deficits. They usually present as symptoms of spinal cord compression, peripheral nerve palsy or central nervous system metastases. The aim of the study was to analyze retrospectively the frequency and characteristics of neurological disorders in patients with NB, treated in the Department of Paediatrics, Oncology, Haematology and Endocrinology, Medical University of Gdansk, Poland, between 1992 and 2004. MATERIAL AND METHODS: 53 children with NB, aged 1 month to 10 years 10 months were included in the study. RESULTS: Neurological symptoms were present in 16 children (30%), all with advanced NB (stages III and IV). In 12 of them neurological deficits predominated in the medical history, contributing to the neoplasm's diagnosis. Most of the patients (10 children) demonstrated symptoms of the lower limbs paresis and bladder/bowel sphincter dysfunction. Four children suffered from severe back pain. Mentioned neurological disorders preceeded NB diagnosis for median period of 2,5 months. In three patients neurological complications of surgical tumour resection occurred (Horner syndrome in two and foot dorsiflexorparesis in one child). No neurological side effects of chemo- and radiotherapy were observed. Neurological symptoms recovered completely with oncological treatment in eight patients, while in three a considerable neurological improvement was observed. No recovery of neurological deficits was obtained in patients with post-surgical complications and in children suffering from disease progression. Three patients died of NB dissemination, 13 children are alive including two patients undergoing therapy. CONCLUSIONS: 1. Most of NB patients recovered completely or partly from neurological disorders while on therapy. Persistent symptoms of neurogenic bladder with accompanying urinary tract infections constitute a considerable clinical problem in some children. 2. NB survivors require intensive interdisciplinary medical care of paediatric oncologist, neurologist, and nephrologist.


Subject(s)
Nervous System Diseases/diagnosis , Nervous System Diseases/etiology , Nervous System Neoplasms/secondary , Neuroblastoma/diagnosis , Neuroblastoma/secondary , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Nervous System Diseases/therapy , Nervous System Neoplasms/therapy , Neuroblastoma/complications , Neuroblastoma/pathology , Neuroblastoma/therapy , Paresis/etiology , Paresis/therapy , Poland , Retrospective Studies , Severity of Illness Index , Spinal Cord Compression/etiology , Spinal Cord Compression/therapy , Survival Analysis , Urinary Tract Infections/etiology , Urinary Tract Infections/therapy
17.
J Postgrad Med ; 50(3): 202-4, 2004.
Article in English | MEDLINE | ID: mdl-15377807

ABSTRACT

Lateral cervical cysts containing squamous cell carcinoma is a diagnostic and therapeutic challenge for the clinician since they usually represent a cystic metastasis from an occult carcinoma. Various imaging modalities or even blind biopsies will help identify the primary tumour. If the primary tumour is identified, an appropriate treatment decision can be made that incorporates both the primary tumour and the cervical node. If the primary remains unidentified, the neck is treated with a modified or radical neck dissection, depending on the extent of metastatic disease, and radiation therapy is administered to Waldeyer's ring and both necks. We present in this paper, a case with a large cervical cyst where histology showed the presence of a poorly differentiated squamous cell carcinoma in the wall of the cyst. A diagnostic evaluation of the patient was negative. Blind biopsies of the right tonsil revealed occult squamous cell carcinoma. The patient was treated by combined chemo/radiotherapy and she is doing well nine months following excision of the mass. The relevant literature is briefly reviewed.


Subject(s)
Brachial Plexus/pathology , Carcinoma, Squamous Cell/secondary , Carcinoma/secondary , Neoplasms, Unknown Primary/diagnosis , Nervous System Neoplasms/secondary , Tonsillar Neoplasms/secondary , Carcinoma/diagnosis , Carcinoma, Squamous Cell/diagnosis , Female , Humans , Middle Aged , Nervous System Neoplasms/diagnosis , Tonsillar Neoplasms/diagnosis
18.
J Clin Oncol ; 22(14): 2909-17, 2004 Jul 15.
Article in English | MEDLINE | ID: mdl-15254060

ABSTRACT

PURPOSE: To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain. PATIENTS AND METHODS: One hundred twenty-one consecutive patients with neuropathic pain due to cancer, partially controlled with systemic opioids, participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose. Extra opioid doses were available as needed. Zero to 10 numerical scale was used to rate average daily pain. The average pain score over the whole follow-up period was used as main outcome measure. Secondary outcome measures were: intensity of burning pain, shooting/lancinating pain, dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes of lancinating pain, presence of allodynia, and daily extra doses of opioid analgesics. RESULTS: Overall, 79 patients received gabapentin and 58 (73%) completed the study; 41 patients received placebo and 31 (76%) completed the study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin (pain score, 4.6) and placebo group (pain score, 5.4; P =.0250). Among secondary outcome measures, dysesthesia score showed a statistically significant difference (P =.0077; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessments). Reasons for withdrawing patients from the trial were adverse events in six patients (7.6%) receiving gabapentin and in three patients receiving placebo (7.3%). CONCLUSION: Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids.


Subject(s)
Acetates/therapeutic use , Amines , Analgesics/therapeutic use , Cyclohexanecarboxylic Acids , Nervous System Neoplasms/complications , Pain/drug therapy , gamma-Aminobutyric Acid , Aged , Analgesics, Opioid/therapeutic use , Double-Blind Method , Female , Gabapentin , Humans , Male , Middle Aged , Neoplasm Invasiveness , Nerve Compression Syndromes/etiology , Nervous System Neoplasms/secondary , Pain/etiology , Pain Measurement , Treatment Outcome
19.
J Radiol ; 85(5 Pt 1): 599-609, 2004 May.
Article in French | MEDLINE | ID: mdl-15205650

ABSTRACT

The natural history of bronchogenic carcinoma shows that 42% of patients are diagnosed with cancer-related neurological complications either at initial presentation or at follow-up that can be separated in 3 different categories: - locoregional involvement of cervicothoracic nerves (recurrent laryngeal nerves, phrenic and vagus nerves, brachial plexus and sympathetic cervical chains), - metastatic disease characterized by intracranial lesions (brain, meningeal, ependymal and pituitary metastases) and spinal (extradural, subarachnoid and medullary metastases) lesions, - paraneoplastic syndromes including limbic encephalitis, Lambert-Eaton syndrome and paraneoplastic cerebellar degeneration. These neurological disorders usually are associated with advanced cancer for which radical surgical management seldom is indicated. All imaging studies performed at the time of initial staging for bronchogenic carcinoma should therefore be carefully reviewed in order to detect signs that could suggest the presence of one or several neurological complications. The goals of this paper are to describe the clinical signs and to illustrate the imaging features of neurological complications related to bronchogenic carcinoma at conventional radiography, CT and MRI.


Subject(s)
Carcinoma, Bronchogenic/diagnosis , Lung Neoplasms/pathology , Nervous System Neoplasms/diagnosis , Carcinoma, Bronchogenic/secondary , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/secondary , Cranial Nerve Neoplasms/diagnosis , Cranial Nerve Neoplasms/secondary , Humans , Lambert-Eaton Myasthenic Syndrome/diagnosis , Lambert-Eaton Myasthenic Syndrome/etiology , Limbic Encephalitis/diagnosis , Limbic Encephalitis/etiology , Magnetic Resonance Imaging , Neoplasm Staging , Nervous System Neoplasms/secondary , Neuroradiography , Paraneoplastic Syndromes, Nervous System/diagnosis , Paraneoplastic Syndromes, Nervous System/etiology , Peripheral Nervous System Neoplasms/diagnosis , Peripheral Nervous System Neoplasms/secondary , Tomography, X-Ray Computed
20.
Head Neck ; 26(4): 322-30, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15054735

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the local control, pattern of recurrence, overall survival, and prognostic factors of patients with squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma of the paranasal sinuses (PNS) and nasal cavity (NC) presenting to our center for curative treatment over a 10-year period. METHODS: Between 1991 and 2000, 60 patients with SCC (n = 32), adenocarcinoma (n = 25), and undifferentiated carcinoma (n = 3) of the PNS or NC were identified. Forty patients received surgery and postoperative radiotherapy, four surgery alone; 11, radiotherapy alone; three radical radiotherapy after surgical recurrence; one, chemoradiotherapy and surgery; and one, induction chemotherapy followed by radiotherapy. RESULTS: Forty-seven patients (78%) were seen with T3-4 disease; however, most (92%) were node negative on initial assessment. The predominant failure pattern was local disease persistence or recurrence. The estimated 2- and 5-year local control rates were 63% and 49%, respectively. Orbital and neural invasion significantly affected local control. The estimated 2- and 5 year overall survival rates were 57% and 40%, respectively. CONCLUSIONS: Local failure remains the dominant cause for poor outcome in this group of patients. Because of the proximity of critical normal structures, the ability to perform adequate surgery and to deliver effective radiotherapy is limited in many cases. The use of postoperative concurrent chemoradiotherapy warrants further investigation.


Subject(s)
Carcinoma/mortality , Nasal Cavity/pathology , Nose Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Australia/epidemiology , Blindness/etiology , Carcinoma/pathology , Carcinoma/therapy , Chemotherapy, Adjuvant , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Nervous System Neoplasms/secondary , Nose Neoplasms/pathology , Nose Neoplasms/therapy , Orbital Neoplasms/secondary , Prognosis , Radiotherapy, Adjuvant , Survival Rate
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