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1.
Biosci Rep ; 41(9)2021 09 30.
Article in English | MEDLINE | ID: mdl-34467977

ABSTRACT

OBJECTIVE: Renal cell carcinoma is prone to early metastasis. In general, intraocular metastasis (IOM) is not common. In the present study, we studied the relationship between different biochemical indicators and the occurrence of IOM in renal cancer patients, and identified the potential risk factors. METHODS: A retrospective analysis of the clinical data of 214 patients with renal cell carcinoma from October 2001 to August 2016 was carried out. The difference and correlation of various indicators between the two groups with or without IOM was analyzed, and binary logistic regression analysis was used to explore the risk factors of IOM in renal cancer patients. The diagnostic value of each independent related factor was calculated according to the receiver operating curve (ROC). RESULTS: The level of neuron-specific enolase (NSE) in renal cell carcinoma patients with IOM was significantly higher than that in patients without IOM (P<0.05). There was no significant difference in alkaline phosphatase (ALP), hemoglobin (Hb), serum calcium concentration, α fetoprotein (AFP), carcinoembryonic antigen (CEA), CA-125 etc. between IOM group and non-IOM (NIOM) group (P>0.05). Binary logistic regression analysis showed that NSE was an independent risk factor for IOM in renal cell carcinoma patients (P<0.05). ROC curve shows that the factor has high accuracy in predicting IOM, and the area under the curve (AUC) is 0.774. The cut-off value of NSE was 49.5 U/l, the sensitivity was 72.2% and the specificity was 80.1%. CONCLUSION: NSE concentration is a risk factor for IOM in patients with renal cell cancer. If the concentration of NSE in the patient's body is ≥49.5 U/l, disease monitoring and eye scans should be strengthened.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Renal Cell/blood , Eye Neoplasms/blood , Kidney Neoplasms/blood , Phosphopyruvate Hydratase/blood , Adult , Aged , Carcinoma, Renal Cell/secondary , Eye Neoplasms/secondary , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Reproducibility of Results , Retrospective Studies , Risk Assessment , Risk Factors
2.
Ann Biol Clin (Paris) ; 78(5): 527-536, 2020 10 01.
Article in French | MEDLINE | ID: mdl-33026348

ABSTRACT

We report the case of a man with a primary diagnosis of Waldenström macroglobulinemia. He secondarily presented a diffuse large B cell lymphoma (DLBCL) located in the nasal fossae, which relapsed later in the eye. The diagnosis of these two malignancies is based on a multidisciplinary biological approach using new sensitive and specific techniques. These techniques revealed that the two diseases harbor different B cell clones, indicating a distinct origin. This observation highlights the importance of targeted biological techniques for the diagnosis of these two rare hemopathies. It also shows that it is possible to prove the independent nature of the two tumor clones, thus allowing optimized therapeutic management.


Subject(s)
Carcinoma, Transitional Cell/diagnosis , Eye Neoplasms/secondary , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/pathology , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Urinary Bladder Neoplasms/diagnosis , Waldenstrom Macroglobulinemia/diagnosis , Aged , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/complications , Diagnosis, Differential , Eye Neoplasms/blood , Eye Neoplasms/diagnosis , Hematologic Tests , Humans , Immunoglobulin M/analysis , Immunoglobulin M/blood , Immunophenotyping , Incidental Findings , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/complications , Male , Monoclonal Gammopathy of Undetermined Significance/blood , Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/pathology , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/complications , Urothelium/pathology , Vision, Low/diagnosis , Vision, Low/etiology , Waldenstrom Macroglobulinemia/blood , Waldenstrom Macroglobulinemia/complications , Waldenstrom Macroglobulinemia/pathology
3.
Dis Markers ; 2020: 2102158, 2020.
Article in English | MEDLINE | ID: mdl-32685054

ABSTRACT

The purpose of this study was to detect clinical variations between lung adenocarcinoma patients with and without ocular metastasis (OM) to identify risk factors for OM and assess the diagnostic values. We included 1153 patients with lung adenocarcinoma in this study. Independent t-tests and chi-square tests were used to compare patients' clinical characteristics. Statistically significant parameters were analyzed by binary logistic regression to detect risk factors of OM. The results showed that the OM group had increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21-1), carbohydrate antigen- (CA-) 125, CA-153, and total prostate-specific antigen (TPSA) compared with the NOM group. CYFRA21-1 is the most useful biomarker for detecting OM in this population.


Subject(s)
Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/blood , Eye Neoplasms/secondary , Lung Neoplasms/pathology , Adenocarcinoma of Lung/therapy , Antigens, Neoplasm/blood , Area Under Curve , CA-125 Antigen/blood , Eye Neoplasms/blood , Female , Humans , Keratin-19/blood , Lung Neoplasms/therapy , Male , Middle Aged , Retrospective Studies , Risk Factors
4.
Biosci Rep ; 40(6)2020 06 26.
Article in English | MEDLINE | ID: mdl-32584390

ABSTRACT

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a tumor that is commonly found in southern China. NPC has several risk factors, such as infection with the Epstein-Barr virus. However, we know little about the risk factors for eye metastasis (EM) in male patients with NPC. Serum lipids are well recognized as risk factors for cardiovascular disease, and recent studies show that they also have a relationship with the development of NPC. PURPOSE: We designed the present study to determine whether they were relevant with the development of EM in male NPC patients by detecting the levels of several serum lipids. METHODS: A total of 1140 male patients with NPC were enrolled in this retrospective study and we divided them into two groups: the metastasis (EM) group and non-eye metastasis (NEM) group. A variety of serum lipids between the two groups were tested and compared. RESULTS: There were statistical differences in the levels of serum TG and TC between these two groups. Binary logistic regression showed that TG and TC were independent risk factors for EM in male NPC patients with P=0.004 and P<0.001, respectively. The area under the curve of TG and TC were 0.764 and 0.681, respectively, using cutoff values of 0.975 and 3.425 mmol/l, respectively. We found that TG had higher sensitivity and specificity values with 87.5% and 62.7%, respectively, than TC which were 50.0% and 87.2%. CONCLUSION: TG and TC are potential risk factors for eye metastases in male NPC patients.


Subject(s)
Cholesterol/blood , Eye Neoplasms/blood , Nasopharyngeal Carcinoma/blood , Nasopharyngeal Neoplasms/blood , Triglycerides/blood , Aged , Eye Neoplasms/diagnostic imaging , Eye Neoplasms/secondary , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/secondary , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/pathology , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , Sex Factors
5.
Biosci Rep ; 40(2)2020 02 28.
Article in English | MEDLINE | ID: mdl-32090248

ABSTRACT

Background Primary liver cancer (PLC) is a common type of cancer among men worldwide. Little is known regarding the relationship of liver cancer with ocular metastasis (OM). Drinking has been also reported to be related not only to the occurrence of liver cancer but also to the causes of some ocular lesions. Purpose A diagnostic standard for the levels of serum biomarkers associated with OM derived from liver cancer in men is urgently needed. Material and methods We examined the association between OM in liver cancer and its serum biomarkers. A total of 1254 male patients with liver cancer were recruited in this retrospective study between July 2002 and December 2012. We assessed the relationship between drinking preference and OM in male patients with liver cancer, and aimed to identify an independent prognostic factor or establish a quantitative indicator for OM. Results By assessing the potential indicators, carbohydrate antigen-125 (CA-125), calcium, and hemoglobin (Hb) were found to be most valuable in the diagnosis of OM in male patients with liver cancer. Conclusion CA-125, calcium, and Hb are independent risk factors of OM in patients with liver cancer who consume alcohol.


Subject(s)
CA-125 Antigen/blood , Calcium/blood , Eye Neoplasms/blood , Hemoglobins/analysis , Liver Neoplasms/blood , Membrane Proteins/blood , Alcohol Drinking/adverse effects , Eye Neoplasms/secondary , Humans , Liver Neoplasms/etiology , Liver Neoplasms/pathology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors
6.
Cancer Med ; 9(4): 1279-1286, 2020 02.
Article in English | MEDLINE | ID: mdl-31218849

ABSTRACT

Lung cancer is prone to metastasis to various organs. Although intraocular metastasis (IOM) occurs at a later stage than metastasis to other organs, it often adversely affects the quality of life and suggests a poor prognosis. In this study, we selected 1608 patients with lung cancer who had metastasis to at least one site and explored clinical differences between those with IOM and non-IOM (NIOM). An independent t test and chi-squared test were used to analyze the clinical features of the patients. The statistically significant parameters were analyzed by binary logistic regression to determine the risk factors for IOM. A receiver operating characteristic curve was constructed to assess their diagnostic value in IOM. The results showed that no significant differences were noted in age, gender, and pathological type between the IOM and NIOM groups. However, the IOM group had higher levels of alpha-fetoprotein, carcinoembryonic antigen, cancer antigen (CA)-125, CA-153, cytokeratin fragment 19 (CYFRA 21-1), and total prostate-specific antigen, compared with the NIOM group. Binary logistic regression indicated that CA-153 and CYFRA 21-1 were risk factors for IOM in patients with MLC (P < 0.05). Area under the curve of CA-153, CYFRA 21-1 and their combination were 0.791, 0.860, and 0.872 respectively. The cutoff values for CA-153 and CYFRA 21-1 were 22.2 U/mL and 6.785 ng/mL. In conclusion, both CA-153 and CYFRA 21-1 were independent risk factors for IOM in patients with metastatic lung cancer (MLC), whereas the combination of CA-153 and CYFRA 21-1 assessment yields the most value in the detection of IOM in patients with MLC.


Subject(s)
Adenocarcinoma of Lung/diagnosis , Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Eye Neoplasms/diagnosis , Keratin-19/blood , Lung Neoplasms/pathology , Mucin-1/blood , Adenocarcinoma of Lung/blood , Adenocarcinoma of Lung/secondary , Eye Neoplasms/blood , Eye Neoplasms/secondary , Female , Humans , Lung Neoplasms/blood , Male , Middle Aged , Prognosis , ROC Curve , Risk Factors
8.
World Neurosurg ; 109: 294, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28987847

ABSTRACT

We report a case of Mikulicz disease (MD), an immunoglobulin G4 (IgG4)-related disease that affects the lacrimal and salivary glands. IgG4-related disease is a relatively new clinical entity and is not commonly encountered by neurosurgeons. MD sometimes mimics intraorbital tumors such as malignant lymphoma but responds well to corticosteroid treatment. Thus it is important to recognize the clinical and radiographic features of MD.


Subject(s)
Eye Neoplasms/diagnostic imaging , Lacrimal Apparatus/diagnostic imaging , Mikulicz' Disease/diagnostic imaging , Aged , Anti-Inflammatory Agents/therapeutic use , Diagnosis, Differential , Eye Neoplasms/blood , Female , Humans , Immunoglobulin G/blood , Magnetic Resonance Imaging , Mikulicz' Disease/blood , Mikulicz' Disease/drug therapy , Prednisolone/therapeutic use , Treatment Outcome
9.
Biomed Res Int ; 2017: 8920350, 2017.
Article in English | MEDLINE | ID: mdl-28573144

ABSTRACT

OBJECTIVES: To investigate the prevalence of laboratory critical results (CRs) and associated risk factors in patients with eye diseases in a tertiary eye hospital. METHODS: Blood samples were collected from both inpatients and outpatients at Zhongshan Ophthalmic Center, Guangzhou, China, from June 1, 2012, to May 31, 2014, and samples were sent to the hospital's clinical laboratory for blood routine, biochemistry, and blood coagulation tests. Laboratory CRs for blood glucose, sodium, potassium, white blood cell count, platelet count, prothrombin time, fibrinogen, international normalized ratio, and activated partial thromboplastin time were included in the current analysis. RESULTS: A total of 60403 subjects were enrolled in the current analysis. CRs were identified in 339 tests from 336 patients with a prevalence of 5.7‰. Age was positively associated with the presence of CRs. Compared to patients with lens diseases, patients with strabismus, oculoplastics, and ocular trauma were less likely to have CRs (P < 0.05), while patients with tumors were more likely to have CRs (P < 0.001). CONCLUSIONS: The prevalence of CRs in eye patients is low but calls for medication attention. It is important for medical personnel, especially ophthalmologists, to increase awareness of the importance, as well as the prevalence and risk factors of CRs.


Subject(s)
Eye Diseases/blood , Eye Diseases/epidemiology , Eye Neoplasms/blood , Prognosis , Adult , Blood Glucose , China/epidemiology , Eye Diseases/pathology , Eye Neoplasms/pathology , Female , Fibrinogen/metabolism , Hospitals , Humans , International Normalized Ratio , Leukocyte Count , Male , Middle Aged , Platelet Count , Potassium/blood , Prothrombin Time , Risk Factors , Sodium/blood
10.
Arch Soc Esp Oftalmol ; 91(8): 379-84, 2016 Aug.
Article in English, Spanish | MEDLINE | ID: mdl-27021801

ABSTRACT

OBJECTIVES: To report the benefits of genetic diagnosis in patients with retinoblastoma. METHOD: Observational study. Patients with retinoblastoma and their families were included. Demographic and clinical data were recorded. Blood and tumour samples were obtained. Next generation sequencing was performed on the samples. When deletion 13 q syndrome was suspected, cytogenetics microarray was performed (Cytoscan® HD, Affymetrix, Santa Clara, CA, USA), with a high density chip of 1.9 million of non-polymorphic probes and 750 thousand SNP probes. RESULTS: Of the 7 cases were analysed 4 were male. The mean age at diagnosis was 21 months (range 5-36). Three cases had bilateral retinoblastoma, and 4 unilateral. None had family history. In all patients, blood was analysed, and a study was performed on the tissue from 2 unilateral enucleated tumours, in which 6 mutations were identified, all de novo. Just one was novel (c.164delC; case 1). One case of unilateral tumour revealed blood mosaicism, showing that his condition was inheritable, and that there is a high risk of developing retinoblastoma in the unaffected eye. The patient also has an increased risk of presenting with other primary tumours. CONCLUSION: Molecular diagnosis of RB1 in patients with retinoblastoma impacts on the decision process, costs, treatment, and prognosis of patients, as well as their families.


Subject(s)
DNA, Neoplasm/genetics , Eye Neoplasms/genetics , Genes, Retinoblastoma , Oligonucleotide Array Sequence Analysis , Retinoblastoma Binding Proteins/genetics , Retinoblastoma/genetics , Ubiquitin-Protein Ligases/genetics , Child, Preschool , Chile , Chromosome Deletion , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Chromosomes, Human, Pair 13/genetics , DNA Mutational Analysis , DNA, Neoplasm/blood , DNA, Neoplasm/isolation & purification , Eye Neoplasms/blood , Eye Neoplasms/chemistry , Eye Neoplasms/diagnosis , Female , Humans , Infant , Male , Mosaicism , Mutation , Neoplasms, Multiple Primary/blood , Neoplasms, Multiple Primary/chemistry , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/genetics , Polymorphism, Single Nucleotide , Retinoblastoma/blood , Retinoblastoma/chemistry , Retinoblastoma/diagnosis , Sequence Analysis, DNA/methods
11.
Arch Soc Esp Oftalmol ; 90(12): 562-5, 2015 Dec.
Article in English, Spanish | MEDLINE | ID: mdl-26279484

ABSTRACT

OBJECTIVE: To determine the importance of intratumoral genetic analysis in the diagnosis of germ-line mutations in patients with retinoblastoma. To underline the importance of performing these genetic tests in every case of retinoblastoma. METHOD: Intratumoral genetic analysis of RB1 mutation was performed on 17 enucleated eyes that were non-responsive to conservative treatment. Patients had no family history of retinoblastoma, and lesions were always single. The identified mutations were then also studied in peripheral blood analysis. RESULTS: There were 12 (70.6%) cases with positive results in intratumoral analysis. In 8 cases (47.1%) mutation of both RB1 alelli were detected, and in 4 (23.5%) cases only one allele was found mutated. In 5 patients (29.4%) no mutation was identified. In the first hit, mutations comprised 7 frameshift or nonsense and 2 splice, whereas in the second hit, one splice mutation, 2 nonsense and 8 loss of heterozygosity were identified. Among 6 patients where intratumoral analysis detected a single mutation associated with a loss of heterozygosity, the peripheral blood analysis was able to detect the same mutation in 3 cases (50%). CONCLUSIONS: Intratumoral genetic analysis of sporadic retinoblastoma can detect germ-line mutations. These patients are at higher risk of bilateralization and development of second tumors or trilateral retinoblastoma. Genetic screening is recommended in every patient diagnosed with retinoblastoma.


Subject(s)
Eye Neoplasms/genetics , Mutation , Retinoblastoma/genetics , Alleles , DNA Mutational Analysis , Eye Enucleation , Eye Neoplasms/blood , Eye Neoplasms/chemistry , Eye Neoplasms/surgery , Genes, Retinoblastoma , Genetic Testing , Germ-Line Mutation , Humans , Loss of Heterozygosity , Neoplasm Proteins/blood , Neoplasm Proteins/genetics , Organ Specificity , Retinoblastoma/blood , Retinoblastoma/chemistry , Retinoblastoma/surgery , Retinoblastoma Binding Proteins/analysis , Retinoblastoma Binding Proteins/blood , Retinoblastoma Binding Proteins/genetics , Retinoblastoma Protein/blood , Retinoblastoma Protein/genetics , Ubiquitin-Protein Ligases/analysis , Ubiquitin-Protein Ligases/blood , Ubiquitin-Protein Ligases/genetics
12.
Ann Hematol ; 93(8): 1287-95, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24633660

ABSTRACT

We have performed a retrospective analysis of all patients with extragastric mucosa-associated lymphoid tissue (MALT) lymphoma treated at our institution to compare the efficacy of first-line therapeutic modalities including surgery, radiation, systemic therapy, and antibiotics. One hundred eighty-five patients with extragastric MALT lymphoma with a median age of 63 (interquartile range (IQR) 50-74) years and a median follow-up time of 49 (IQR 18-103) months were retrospectively analyzed. Time to progression and time to next therapy were used as surrogate endpoints for efficacy. Patients having either surgery (100 %), chemo/immunotherapy (85.5 %), or radiation (80 %) had significantly (p = 0.01) higher response rates than patients treated with antibiotics (33.3 %). Patients who were irradiated had significantly more progressive disease, but also the longest follow-up time. Stage, elevated LDH, anemia, elevated beta-2 microglobulin, plasmacytic differentiation, monoclonal gammopathy, or autoimmune disease did not influence the rate of disease progression nor did complete remission or partial remission from initial therapy influence time to and rate of progression. There was no significant difference in the median time to progression (p = 0.141), but the estimated time to progression (p = 0.023) as well as the estimated time to next therapy (p = 0.021) was significantly different among the various cohorts favoring surgery, chemo/immunotherapy, and radiation. Our results suggest extragastric MALT lymphoma as a potential systemic disease irrespective of initial stage. Radiation, surgery, and chemo/immunotherapy seem to be equally effective in achieving remissions and prolonged progression free survivals, but a curative potential is questionable. Localized MALT lymphomas affecting the thyroid gland or the lungs have excellent long-term progression-free survivals with surgical treatment only.


Subject(s)
Lymphoma, B-Cell, Marginal Zone/therapy , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Austria/epidemiology , Colorectal Neoplasms/blood , Colorectal Neoplasms/mortality , Colorectal Neoplasms/therapy , Combined Modality Therapy , Disease Progression , Disease-Free Survival , Eye Neoplasms/blood , Eye Neoplasms/mortality , Eye Neoplasms/radiotherapy , Eye Neoplasms/surgery , Eye Neoplasms/therapy , Humans , Immunotherapy , Kaplan-Meier Estimate , Lung Neoplasms/blood , Lung Neoplasms/mortality , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Lung Neoplasms/therapy , Lymphoma, B-Cell, Marginal Zone/blood , Lymphoma, B-Cell, Marginal Zone/mortality , Lymphoma, B-Cell, Marginal Zone/radiotherapy , Lymphoma, B-Cell, Marginal Zone/surgery , Middle Aged , Organ Specificity , Retrospective Studies , Salivary Gland Neoplasms/blood , Salivary Gland Neoplasms/mortality , Salivary Gland Neoplasms/radiotherapy , Salivary Gland Neoplasms/surgery , Salivary Gland Neoplasms/therapy , Thyroid Neoplasms/blood , Thyroid Neoplasms/mortality , Thyroid Neoplasms/surgery , Thyroid Neoplasms/therapy , Treatment Outcome
13.
Article in English | MEDLINE | ID: mdl-23984285

ABSTRACT

OBJECTIVES: To investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development. BACKGROUND: The increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population). Search for new biological markers is important for diagnosis and prognosis in eye tumors. Cystatin C, an endogenous inhibitor of cysteine proteases, plays an important protective role in several tumors. Lactoferrin was shown to express anti-tumor and antiviral activities. It was hypothesized that cystatin C and lactoferrin could serve as possible biomarkers in the diagnosis of malignant and benign eye tumors. STUDY DESIGN: A total of 54 patients with choroidal melanoma and benign eye tumors were examined (part of them undergoing surgical treatment). Serum, tear fluid and intraocular fluid samples obtained from the anterior chamber of eyes in patients with choroidal melanoma were studied. METHODS: Cystatin C concentration in serum and eye biological fluids was measured by commercial ELISA kits for human (BioVendor, Czechia); lactoferrin concentration--by Lactoferrin-strip D 4106 ELISA test systems (Vector-BEST, Novosibirsk Region, Russia). RESULTS: Cystatin C concentration in serum of healthy persons was significantly higher as compared to tear and intraocular fluids. In patients with choroidal melanoma, increased cystatin C concentration was similar in tear fluid of both the eyes. Lactoferrin level in tear fluid of healthy persons was significantly higher than its serum level. Significantly increased lactoferrin concentration in tear fluid was noted in patients with benign and malignant eye tumors. CONCLUSION: Increased level of cystatin C in tear fluid seems to be a possible diagnostic factor in the eye tumors studied. However, it does not allow us to differentiate between malignant and benign eye tumors. Similar changes were noted for lactoferrin in tear fluid.


Subject(s)
Cystatin C/analysis , Eye Neoplasms/diagnosis , Lactoferrin/analysis , Adult , Aged , Aged, 80 and over , Aqueous Humor/chemistry , Biomarkers/analysis , Biomarkers/blood , Case-Control Studies , Choroid Neoplasms/blood , Choroid Neoplasms/diagnosis , Cystatin C/blood , Eye Neoplasms/blood , Female , Humans , Lactoferrin/blood , Male , Melanoma/blood , Melanoma/diagnosis , Middle Aged , Tears/chemistry
14.
Biomedica ; 33(1): 53-61, 2013.
Article in English | MEDLINE | ID: mdl-23715307

ABSTRACT

INTRODUCTION: Retinoblastoma is a childhood cancer of the retina originated by altered or null retinoblastoma protein (pRb) expression. Genetic alterations in both RB1 alleles in the retinal cells are required for the development of retinoblastoma. In the sporadic form, non-hereditary RB1 gene mutations take place in a single retinoblast cell, and are therefore only present in tumor DNA (somatic mutations). Sporadic retinoblastoma is primarily unilateral, lacks family history and has no risk of transmission to descendants. Genetic tests for detection of RB1 mutation has improved the identification of carriers and facilitated accurate genetic counseling. OBJECTIVE: To identify mutations in the RB1 gene in Colombian patients with sporadic retinoblastoma by PCR-SSCP followed by sequence. MATERIALS AND METHODS: Four patients with sporadic retinoblastoma were analyzed by PCR-SSCP, followed by DNA sequencing to identify variations in the RB1 gene. RESULTS: We identified five variations in RB1 gene: three new mutations (one germline and two somatic mutations), one new polymorphism and one already reported somatic mutation. Four mutations were found in three patients with unilateral retinoblastoma and one mutation was found in a patient with bilateral retinoblastoma. One of these was a germline mutation in a sporadic unilateral retinoblastoma that was not present in the parents or three siblings analyzed. CONCLUSIONS: Our results emphasize the importance of identifying mutations for genetic counseling and clinical management of sporadic retinoblastoma patients. Description of a new RB1 gene variant is interesting since there have been a small number of polymorphisms reported for this gene.


Subject(s)
Eye Neoplasms/genetics , Genes, Retinoblastoma , Mutation , Retinoblastoma/genetics , Child, Preschool , DNA Mutational Analysis , DNA, Neoplasm/analysis , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , Eye Neoplasms/blood , Female , Frameshift Mutation , Germ-Line Mutation , Humans , Infant , Male , Neoplasms, Multiple Primary/blood , Neoplasms, Multiple Primary/genetics , Pedigree , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Retinoblastoma/blood , Sequence Analysis, DNA
15.
Biomédica (Bogotá) ; 33(1): 53-61, ene.-mar. 2013. ilus, tab
Article in English | LILACS | ID: lil-675132

ABSTRACT

Introduction. Retinoblastoma is a childhood cancer of the retina originated by altered or null retinoblastoma protein (pRb) expression. Genetic alterations in both RB1 alleles in the retinal cells are required for the development of retinoblastoma. In the sporadic form, non-hereditary RB1 gene mutations take place in a single retinoblast cell, and are therefore only present in tumor DNA (somatic mutations). Sporadic retinoblastoma is primarily unilateral, lacks family history and has no risk of transmission to descendants. Genetic tests for detection of RB1 mutation has improved the identification of carriers and facilitated accurate genetic counseling. Objective. To identify mutations in the RB1 gene in Colombian patients with sporadic retinoblastoma by PCR-SSCP followed by sequence. Materials and methods. Four patients with sporadic retinoblastoma were analyzed by PCR-SSCP, followed by DNA sequencing to identify variations in the RB1 gene. Results. We identified five variations in RB1 gene: three new mutations (one germline and two somatic mutations), one new polymorphism and one already reported somatic mutation. Four mutations were found in three patients with unilateral retinoblastoma and one mutation was found in a patient with bilateral retinoblastoma. One of these was a germline mutation in a sporadic unilateral retinoblastoma that was not present in the parents or three siblings analyzed. Conclusions. Our results emphasize the importance of identifying mutations for genetic counseling and clinical management of sporadic retinoblastoma patients. Description of a new RB1 gene variant is interesting since there have been a small number of polymorphisms reported for this gene.


Introducción. El retinoblastoma es un cáncer pediátrico de la retina originado por la expresión alterada o ausente de la proteína del retinoblastoma (pRb). Se requiere la alteración genética de ambos alelos RB1 en las células de la retina para el desarrollo del retinoblastoma. En la forma esporádica, las mutaciones no hereditarias del gen RB1 ocurren en un solo retinoblasto y están presentes sólo en el ADN del tumor (mutaciones somáticas). El retinoblastoma esporádico es generalmente unilateral, no tiene historia familiar y no tiene riesgo de transmisión a la descendencia. Las pruebas genéticas para la detección de mutaciones en RB1 han mejorado la identificación de portadores y han facilitado la precisión de la asesoría genética. Objetivo. Detectar mutaciones en el gen RB1 en pacientes colombianos con retinoblastoma esporádico mediante PCR-SSCP seguido de secuenciación. Materiales y métodos. Se analizaron cuatro pacientes con retinoblastoma esporádico para la detección de variaciones en el gen RB1 mediante PCR-SSCP, seguida de secuenciación. Resultados. Se identificaron cinco variaciones del gen RB1 : tres mutaciones nuevas (una de línea germinal y dos somáticas), un polimorfismo nuevo y una mutación somática ya reportada. Las cuatro mutaciones se encontraron en tres pacientes con retinoblastoma unilateral y uno con bilateral. La mutación germinal se detectó en un paciente con compromiso unilateral y no se encontró en los padres ni en los tres hermanos analizados. Conclusión. Estos resultados enfatizan la importancia, para asesoría genética y manejo clínico, de identificar mutaciones del gen RB1 en pacientes con retinoblastoma esporádico. La descripción de una nueva variante en RB1 es interesante, dado el muy bajo número de polimorfismos reportados para este gen.


Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Eye Neoplasms/genetics , Genes, Retinoblastoma , Mutation , Retinoblastoma/genetics , DNA Mutational Analysis , DNA, Neoplasm/analysis , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , Eye Neoplasms/blood , Frameshift Mutation , Germ-Line Mutation , Neoplasms, Multiple Primary/blood , Neoplasms, Multiple Primary/genetics , Pedigree , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Retinoblastoma/blood , Sequence Analysis, DNA
16.
Clin Exp Metastasis ; 30(1): 91-102, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22865235

ABSTRACT

Previously we demonstrated that intraperitoneal (IP) inoculation of Rev-2-T-6 mouse lymphoma into syngeneic Balb/c hosts resulted in brain metastasis, migration along the optic nerve sheath, and ocular infiltration. In a second model: intravitreal inoculation of Rev-2-T-6 cells, the developing lymphoma was largely confined within the eye, seldom breaching the retinal pigment epithelium to reside in the choroid and sclera. There was no retrograde infiltration into the brain. Here, we describe a third, complementary model, whereby intravitreal inoculation of Rev-2-T-6 cells into Balb/c mice, followed by repeated IP inoculations of anti-LFA-1/CD11a monoclonal antibodies, results in extensive infiltration of the choroid, sclera, conjunctiva, eyelids and orbit. Furthermore, the lymphoma cells metastasize along the optic nerve sheath into the brain, and through the contralateral optic nerve tract into the contralateral eye. There is no systemic involvement of the lymphoma. Furthermore, anti-LFA-1 treatment results in elevated levels of serum anti-Rev-2-T-6 antibodies. Inoculation of Rev-2-T-6 cells into the vitreous of severe combined immune deficient mice demonstrates a course of clinical signs and histopathological findings similar to those in immune-competent mice treated with anti-LFA-1 antibodies, including invasion of the contralateral eye. Taken together, these findings suggest that confinement of Rev-2-T-6 lymphoma cells to the eye depends on active immune surveillance using a population of effector cells expressing the cell surface integrin LFA-1. Impairing this protection enhances tumor aggressiveness within the eye, and the likelihood of early retrograde lymphoma metastasis into the brain and the contralateral eye.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Brain Neoplasms/secondary , Eye Neoplasms/secondary , Lymphocyte Function-Associated Antigen-1/immunology , Lymphoma, T-Cell/pathology , Vitreous Body/pathology , Animals , Antibodies, Monoclonal/blood , Blotting, Western , Brain Neoplasms/blood , Brain Neoplasms/immunology , Cell Line, Tumor , Disease Models, Animal , Eye Neoplasms/blood , Eye Neoplasms/immunology , Lymphoma, T-Cell/blood , Lymphoma, T-Cell/immunology , Mice , Mice, Inbred BALB C , Mice, SCID
17.
Cancer Sci ; 101(5): 1199-203, 2010 May.
Article in English | MEDLINE | ID: mdl-20345477

ABSTRACT

This retrospective study was launched to evaluate the efficacy of doxycycline and to find independent predictors of a clinical response in patients with ocular adnexal lymphoma of mucosa-associated lymphoid tissue (OAML). Thirty-eight patients with newly diagnosed, localized OAML received doxycycline for 3 weeks (12 patients) or 6 weeks (26 patients). Clinical factors including absolute lymphocyte count (ALC) and neutrophil count (ANC) were compared between responders and non-responders. After a median follow-up of 26.4 months, doxycycline resulted in an overall response rate of 47% and a 3-year time-to-treatment failure (TTF) rate of 84%. Patients treated with doxycycline for 6 weeks versus 3 weeks tended to have a higher response rate (54%vs 33%). Absolute lymphocytosis (ALC > 3.01 x 10(9)/L) and absolute neutrophilia (ANC > 1.92 x 10(9)/L) were defined based on the median value of each count. Patients with (19 patients) versus without absolute lymphocytosis had significantly shorter 2-year TTF (70%vs 100%, P = 0.021) and a lower response rate (32%vs 63%, P = 0.051). Absolute lymphocytosis (odds ratio [OR] = 4.7; 95% confidence interval [CI], 1.1-20.8; P = 0.043) and non-conjunctival tumor (OR = 11.8; 95% CI, 1.1-122.5; P = 0.038) were negative predictors for response by multivariate analysis. Front-line doxycycline is effective particularly in localized OAML patients without absolute lymphocytosis but with conjunctival involvement.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Doxycycline/therapeutic use , Eye Neoplasms/drug therapy , Lymphoma, B-Cell, Marginal Zone/drug therapy , Adult , Aged , Eye Neoplasms/blood , Female , Humans , Lymphoma, B-Cell, Marginal Zone/blood , Male , Middle Aged , Retrospective Studies , Treatment Failure
18.
Nephrol Ther ; 6(2): 132-6, 2010 Apr.
Article in French | MEDLINE | ID: mdl-20299297

ABSTRACT

Acute renal failure, as the initial manifestation of lymphoma, has been reported only in a few cases. In this work, we report the case of a 28-year-old women admitted for acute renal failure. Her physical examination detected bilateral kidney enlargement. Laboratory evaluation revealed a serum creatinine value 218 micromol/l. A 24-hour urine collection analysis allowed the detection of 1g of protein. No red cells were found after urinanalysis. Renal ultrasound showed massively enlarged kidneys. Renal biopsy of the kidney and pathologic examination showed diffuse infiltration of the interstitium with lymphocytes and atypical cells positive for CD20 markers. A diagnosis of diffuse large B-cell type non-Hodgkin lymphoma was made. However, investigations revealed the presence of two others sites of lymphoma: gastric and ophthalmic. The patient's renal function and kidney size as well as the other lymphoma locations were normalized after the initiation of chemotherapy.


Subject(s)
Acute Kidney Injury/etiology , Eye Neoplasms/diagnosis , Kidney Neoplasms/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Neoplasms, Multiple Primary/diagnosis , Stomach Neoplasms/diagnosis , Adult , Antigens, CD20/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Diagnosis, Differential , Eye Neoplasms/blood , Eye Neoplasms/complications , Eye Neoplasms/drug therapy , Female , Humans , Kidney Neoplasms/blood , Kidney Neoplasms/complications , Kidney Neoplasms/drug therapy , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/drug therapy , Neoplasms, Multiple Primary/blood , Neoplasms, Multiple Primary/drug therapy , Stomach Neoplasms/blood , Stomach Neoplasms/complications , Stomach Neoplasms/drug therapy , Treatment Outcome
19.
Retina ; 30(2): 310-6, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20175273

ABSTRACT

PURPOSE: The purpose of this study was to describe patients initially carrying a diagnosis of primary intraocular lymphoma who were ultimately diagnosed with ocular sarcoidosis. METHODS: The medical records of patients evaluated between 1995 and 2007 fitting the criteria described earlier were identified, and pertinent clinical findings allowing for the diagnosis of sarcoidosis are described. RESULTS: Nine patients between the ages of 52 and 83 were referred with a diagnosis of primary intraocular lymphoma but were ultimately diagnosed with sarcoidosis. The most common clinical signs found in these patients that are atypical for primary intraocular lymphoma but common in sarcoidosis were multifocal choroiditis (n = 7) and cystoid macular edema (n = 6). Additional findings included keratic precipitates, posterior synechiae, and Koeppe nodules. Chest computerized tomography was consistent with sarcoidosis in seven of eight tested patients, and five of these patients had normal chest x-rays. Other findings included elevated angiotensin-converting enzyme and/or lysozyme, and biopsy revealing noncaseating granulomas. CONCLUSION: Although primary intraocular lymphoma should always be in the differential diagnosis of older patients who present with signs of ocular inflammation, ophthalmologists must also consider other etiologies, including sarcoidosis. A chest computerized tomography may be helpful in the diagnosis, particularly when laboratory findings are supportive of sarcoidosis.


Subject(s)
Diagnostic Errors , Eye Diseases/diagnosis , Lymphoma, B-Cell/diagnosis , Sarcoidosis/diagnosis , Vitreous Body/pathology , Aged , Aged, 80 and over , Diagnosis, Differential , Eye Diseases/blood , Eye Neoplasms/blood , Eye Neoplasms/diagnosis , Female , Humans , Lymphoma, B-Cell/blood , Magnetic Resonance Imaging , Male , Middle Aged , Muramidase/blood , Peptidyl-Dipeptidase A/blood , Sarcoidosis/blood , Tomography, X-Ray Computed , Uveitis/blood , Uveitis/diagnosis
20.
J Pediatr Hematol Oncol ; 30(1): 73-6, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18176187

ABSTRACT

Children < or =18 years with malignant proptosis enrolled in ophthalmic tumor clinic at a tertiary cancer center from July 2003 to December 2006 were retrospectively analyzed. The incidence of proptosis among the pediatric cancer patients was 4.9%. Secondary tumors accounted for majority of cases (n=62, 59.6%) with retinoblastoma (51%) being the commonest cause of proptosis. Fourteen (13.5%) patients presented with bilateral proptosis; all but one had metastatic tumor as underlying cause. Metastatic malignancies had significantly lower hemoglobin and platelet count and higher white blood count. Therefore, careful analysis of symptomatology, hemogram, and those with bilateral proptosis warrant a hematologic work-up before imaging studies and invasive orbital biopsy.


Subject(s)
Exophthalmos/epidemiology , Eye Neoplasms/epidemiology , Retinoblastoma/epidemiology , Adolescent , Child , Child, Preschool , Exophthalmos/blood , Exophthalmos/pathology , Eye Neoplasms/blood , Eye Neoplasms/pathology , Eye Neoplasms/secondary , Female , Hemoglobins/analysis , Humans , Incidence , Infant , Leukocyte Count , Male , Neoplasm Metastasis , Platelet Count , Retinoblastoma/blood , Retinoblastoma/pathology , Retrospective Studies
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