Cases Of Retinoblastoma Research Articles

Retinoblastoma in Taiwan: incidence and survival characteristics from 1979 to 2003

To describe the incidence and survival rate of patients with retinoblastoma in Taiwan over a 25-year period, from 1979 to 2003. Cases of retinoblastoma have been reported to the Taiwan National Cancer Registry (TNCR) since 1979. Retinoblastoma data from 1979 to 2003 were retrieved from the TNCR databank for analysis of both the incidence and survival rate. Trends in the incidence rate were estimated by calculating the annual percentage change (APC). From 1979 to 2003, a total of 380 patients (182 [47.9%] females) with retinoblastoma were identified. Of the 380 cases, 359 patients (94.5%) were diagnosed before 5 years of age. The average annual age-standardized incidence rate was 4.45 per million in children under 10 years of age and 8.58 per million in children under 5 years of age. There was a significant increasing trend in the incidence rate over the study period with an APC of 2.3% (P=0.035). Before the implementation of Taiwan's National Health Insurance (NHI) Program in 1995, the mean age at diagnosis was 4.8+/-13.3 years and the 5-year survival rate was 74.7%. After implementation of the NIH Program, the mean age at diagnosis decreased to 1.6+/-2.1 years (P<0.001) and the 5-year survival rate increased to 84.7% (P=0.063). We report the first population-based study on retinoblastoma in Taiwan. There was a significant increasing trend in the incidence rate from 1979 to 2003. Since the implementation of Taiwan's NHI, the mean diagnostic age decreased.

Relationship between heat shock proteins and Survivin in retinoblastoma cells and its effect on the proliferation of the cellular activity

Objective To investigate the relationship of the expression between heat shock protein (HSP) 70 and 90, and Survivin and its effects on the proliferative activity in retinoblastoma (RB) cells. Methods Expression of Survivin, HSP70 and 90, and Ki-67 in conventional paraffin samples from 43 patients with RB and 6 healthy people was detected by streptavidin-biotin peroxidase (SP) immunohistochemical method. Ki-67 labeling index was used to evaluate the proliferative activity in RB. Results In 43 cases of RB, positive expression of HSP70 and 90 and Survivin was found in 28 (65.12%), 37 (86.05%) and 27 (62.79%) cases, respectively. None of the 6 normal retinal tissue expressed HSP70, HSP90 or Survivin. Positive expression of Survivin was more frequent in positive expressions of HSP90 than that in negative expressions of HSP90 (P 0.05). Expression of HSPs and Survivin and Ki-67 labeling index did not correlate with histological types (P>0.05). Conclusion Expression of HSP90 correlates with that of Survivin in RB. Co-existence of Survivin and HSP90 probably plays an important role in the genesis of RB. Key words: Retinoblastoma/pathophysiology; Heat-shock proteins/analysis; Cell proliferation

Short-term observations of the effects of ocular surgery and systemic chemotherapy to treat retinoblastoma

Objective A short-term observation study of ocular surgery with or without systemic chemotherapy to treat retinoblastoma (RB). Method The clinical data of 66 RB cases treated at Beijing Tongren Hospital from August 2006 to September 2007 were retrospective reviewed. All patients received ultrasound (B scan/CDI), radiology examination (CT scan/MRI) and RetCam retina examination, and classified according to the International Intraocular Retinoblastoma Classification (IIRC) method. Focal therapies (include laser and cryotherapy) were applied to Group A, systemic chemotherapy (CCTV protocol, Cyclosporine, Carboplatin, Teneposide and Vincrinstine) plus ocular surgery (include focal therapy, enucleation and orbital exenteration) to Group B, C, D and E. Patients were followed-up for more than 6 months. Result Of 66 cases (36 male/30 female), 16/66 cases were bilateral RB and 50/66 were unilateral. Follow up period was from 6 to 13 months (mean time 8. 6 month). According to IIRC, there were 5 eyes in Group A, 6 eyes in Group B, 5 eyes in Group C, 15 eyes in Group D and 51 eyes in Group E (include extraocular disease). 22/82 eyes were conserved at the end of follow up, including 5/5 (100%) of group A, 6/6(100%) of group B, 5/5(100%) of Group C, 4/15(26.7%) of Group D and 2/51(3.9%) of Group E. 5/66 (7.6%) patients died during this period, they all were in Group E. Conclusion Ocular surgery combined with systemic chemotherapy is an effective method to treat retinoblastoma. The consequences depends on the classification with higher conservative rate of eyeballs in early and middle stage (Group,A, B, C), and lower rate in late stage (Group D and E). Key words: Retinoblastoma/surgery; Retinoblastoma/drug therapy

Sudden Dispersion of Retinoblastoma Shortly after Initial Chemotherapy Treatment

To present 3 cases of unilateral retinoblastoma that demonstrated unusual tumor dispersion shortly after initial chemotherapy treatment. Observational case series. Review of medical records of patients in whom intraocular dissemination of retinoblastoma occurred after initial treatment with chemotherapy. Three patients demonstrated an atypical response with intraocular dissemination of retinoblastoma shortly after 1 cycle of chemotherapy. All cases had unilateral retinoblastoma with no vitreous seeding or subretinal fluid at presentation. In 2 cases (Cases 2 and 3), there were a few distant subretinal seeds. Per the International Classification of Retinoblastoma, 1 tumor was group E (Case 1), and the other 2 tumors were group D1 (Cases 2 and 3). In 2 cases (Cases 1 and 2), chemotherapy included a 2-drug regimen of carboplatin and etoposide; in the third case, a 3-drug regimen of carboplatin, etoposide, and vincristine was used. In each case, the retinoblastoma dispersed with tumor cells in the vitreous shortly after initial chemotherapy treatment, leading to subsequent enucleation of the eye. Retinoblastoma can exhibit an unexpected and sudden dispersion of the tumor shortly after chemotherapy is initiated.

Investigation of themiR16-1(C&gt;T) + 7 Substitution in Seven Different Types of Cancer from Three Ethnic Groups

Background. MicroRNAs are a type of small noncoding RNA molecules that have been shown to control gene expression in eukaryotes. Aberrant expression and alteration of miRNAs may be responsible for human diseases including cancer. An miR16-1 (C > T) + 7 gene mutation has been previously found in familial chronic lymphocytic leukemia patients, one of which reported a family history of breast cancer. miR16-1 regulates the expression of bcl-2, which is important in retinoblastoma, and is located in a genomic region that is frequently lost in nasopharyngeal and hepatocellular carcinomas (HCCs). Therefore, miR16-1 may be potentially important in the etiology of several solid tumors. To understand the power of the miR16-1 (C > T) + 7 mutation as a prognostic and diagnostic risk factor, we investigated the mutation in patients with seven different types of cancer including 188 with breast, 102 with ovarian, and 22 nasopharyngeal carcinomas, 96 HCC, 872 chronic myeloid leukemia (CML), 39 chronic lymphocytic leukemia (CLL), and 46 retinoblastoma cases from three different ethnic groups and of hereditary and sporadic etiology. Methods. 5′Nuclease TaqMan SNP genotyping assay was used to detect the miR16-1 gene C > T substitution. Results. The miR16-1 (C > T) + 7 substitution was not detected in any of the groups studied. Conclusions. Considering the large scale of our study, the representation of different ethnicities and levels of hereditary risk, we conclude that the miR-16-1 (C > T) + 7 mutation is not a good diagnostic or prognostic indicator of risk for the cancers tested.

Expression of heat shock protein 27 and alpha-crystallins in human retinoblastoma after chemoreduction

Aim:Small heat shock proteins (sHSP) play an important role in the resistance to anticancer drugs. We examined the expression of the sHSP family, HSP27 and α-crystallins, in human retinoblastoma with...

Histological determinant of mortality in retinoblastoma in Ibadan

Retinoblastoma remains the most common primary intraocular malignancy of infancy and childhood.1 It is a tumour of primitive neuroectodermal tissue mainly from the nuclear layers of the retina.2 Most retinoblastoma...

Survival with retinoblastoma in the USA: 1975–2004

Background:The purpose of this study was to determine the survival of retinoblastoma in the USA over a 30-year period from 1975 to 2004 using a systematic review of existing databases.Methods:Nine...

Incidence of retinoblastoma in the USA: 1975–2004

Background:The purpose of this study was to determine the age-adjusted incidence of retinoblastoma in the USA over a 30-year period from 1975 to 2004 using a review of existing databases.Methods:Six...

Retinoblastoma bilateral de aparecimento tardio: relato de caso

A case of retinoblastoma with uncommon features is reported, aiming at improving follow-up. In 1993, SJMMF, 9-month-old white boy, presented a squint in the left eye. A retinal tumor was detected. The patient had a family history of retinoblastoma. Enucleation was performed and retinoblastoma was proved. The patient underwent examination for staging, all were normal. The fellow eye remained normal for 10 years. During routine examination the retina map revealed three retinoblastoma white lesions in the nasal retina. The patient underwent transpupillary thermotherapy with diode laser. After 30 days, the lesions became atrophic. After 60 days there was tumor recurrence on the border of the lesion. Sclera cryotherapy was performed. There was tumor regression for six months. During follow-up, condensations next to the atrophic tumor lesions were discovered, which were vitreous seeds. Brachitherapy with 125 iodine was done. The lesions disappeared after 30 days. New vitreous seeds appeared 3 months later, set on the retina surface. They were blocked with sclera cryotherapy and transpupillary thermotherapy. The patient presented with new vitreous seeds after six months, which adhered to the retina. They were blocked with transpupillary thermotherapy. Follow-up was for 38 months since the appearance of the bilateral tumor. The patient presents normal visual acuity and clinical examination. This case is important considering the low frequency of the disease at this age. It is essential to maintain alertness when cases of retinoblastoma are seen as cured.

Management of retinoblastoma with proximal optic nerve enhancement on MRI at diagnosis

In North America, retinoblastoma rarely presents with gross clinical evidence of tumor involving the optic nerve. Extent of microscopic tumor infiltration into the postlaminar optic nerve is a significant risk factor for metastasis, especially if there is tumor at the cut end. Due to poor outcomes in patients with metastatic disease, historical treatment for patients with clinical evidence of extraocular optic nerve involvement has included upfront enucleation followed by aggressive adjuvant chemotherapy. Additional orbital irradiation is advocated for individuals with optic nerve involvement at the surgical margin. Little is known about the role of neoadjuvant therapy in the setting of orbital optic nerve enhancement on magnetic resonance imaging (MRI) at diagnosis. A retrospective review of consecutive retinoblastoma cases at Childrens Hospital Los Angeles over a 3-year period (2004-2006) found to have gadolinium contrast enhancement in the proximal portion of optic nerve on MRI at diagnosis. Nine patients fit the inclusion criteria. Two had secondary glaucoma of a sufficient degree to cause an enlarged eye (buphthalmos). Median age at presentation was 17 months (2-36 months). All patients received neoadjuvant chemotherapy prior to enucleation. Only two received external beam radiation. All are disease-free with a median follow-up of 22 months (12-41 months). Neoadjuvant chemotherapy is well tolerated prior to enucleation of retinoblastoma-containing eyes associated with contrast enhancement of the proximal optic nerve on MRI at diagnosis. Such an approach may be used to decrease intensity or duration of chemotherapy and need for external beam radiation.

Spectrum of RB1 gene mutations and loss of heterozygosity in Mexican patients with retinoblastoma: Identification of six novel mutations

RB1 mutation detection has greatly improved the clinical management of retinoblastoma and provides critical information to predict the risk of inheriting the disease. We screened for RB1 gene sequence alterations in both peripheral blood and tumor specimens from a total of 48 Mexican retinoblastoma patients using an SSCP-based screening approach followed by sequencing. Overall, 21 (43.8%) cases were bilateral and 27 (56.2%) were unilateral. Interestingly, 51.8% of unilateral patients developed the tumor before age 1 year and 10 of which (71.4%) were diagnosed before the age of 6 months. Thirteen different oncogenic mutations were detected in 14/48 (29.2%) patients, 9 of which were germline (64.3%). Six of these mutations are novel (IVS3-1G>T, 125X, 389X, 610X, 750X and -149G>T). The most frequent types of mutation were frameshift and nonsense (30.8% each). Moreover, 5 intronic variants were identified, two of which are novel (g.41908 C/A and g.161976del6T). Loss of heterozygosity of the RB1 gene as assessed by intron1/BamHI and intron17/XbaI intragenic markers was 50.0% (18 of 36 informative cases), being higher in tumors with known mutations (76.9% vs 34.8%). This low mutation detection rate and the earlier age at diagnosis in unilateral retinoblastoma cases suggest that other RB1 inactivating mechanisms could be present in the retinoblastoma development. In this study, mutation analysis was not helpful to distinguish sporadic and hereditary retinoblastoma, so, other approaches are needed to improve the molecular diagnosis of retinoblastoma and supports further investigations of Mexican retinoblastoma patients.

Peripapillary subretinal neovascularization in retinoblastoma

Peripapillary subretinal neovascularization (PSRNV) is a rare type of choroidal neovascularization. Herein we report a case of retinoblastoma complicating PSRNV, and discuss the histopathological findings. A 1-year-old male underwent enucleation of his right eyeball based on the clinical diagnosis of bilateral retinoblastoma after chemotherapy. There was a mass arising from the retina showing highly calcified and necrotic retinoblastoma. The peripapillary region revealed neovascular membrane extending from the optic nerve head to the subretinal space. The membrane included retinal pigment epithelial (RPE) cells and glial cells, as well as endothelial cells. Immunohistochemistry revealed cytokeratin 18-positive RPE cells situated beneath glial fibrillary acidic protein-positive glial cells and their processes. The neovascular membrane did not have a connection with vessels arising from the optic nerve head. There were multiple mound foci made up of proliferated RPE cells in the globe. These results suggest that migration of RPE cells and glial cells plays a crucial role in the pathogenesis of PSRNV, which might be directly or indirectly mediated by retinoblastoma.

Genes and environment: effects on the development of second malignancies in retinoblastoma survivors

Although it is a rare cancer, retinoblastoma has served as an important model in our understanding of genetic cancer syndromes. All patients with a germinal rb1 mutation possess a risk of the development of second malignancies. Approximately 40–50% of all retinoblastoma cases are considered germinal cases and recent work has indicated that nearly all retinoblastoma patients probably demonstrate a degree of mosaicism for the rb1 mutation, and thus are at risk of secondary malignancies. The risk of the development of these cancers continues throughout the patients’ lives due to the loss of a functional RB1 protein and its critical tumor suppressive function in all cells. These cancers can develop in diverse anatomic locations, including the skull and long bones, soft tissues, nasal cavity, skin, orbit, brain, breast and lung. Treatments used for retinoblastoma such as external-beam radiation and chemotherapy can have a significant impact on the risk for and pattern of development of these secondary cancers. Second malignancies are the leading cause of death in germinal retinoblastoma survivors in the USA and thus continue to be an important subject of study in this patient population. Second malignancies following the germinal form of retinoblastoma are the subject of this review.

The Quasi-Integrated Porous Polyethylene Implant in Pediatric Patients Enucleated for Retinoblastoma

Purpose: To describe the clinical outcomes of patients receiving a quasi-integrated porous polyethylene orbital implant following enucleation for retinoblastoma. Methods: A retrospective review of all retinoblastoma patients who received the quasi-integrated porous polyethylene implant following enucleation during the 56-month period between October 2000 and May 2005 was conducted. Results: Ten patients were identified who received the quasi-integrated porous polyethylene implant as a buried, primary orbital implant. Approximately 6 weeks following implantation, a custom-fitted prosthesis was made by an impression technique to provide a “lock-and-key” fit with the orbital implant in the majority of patients. Follow-up ranged from 2 months to 78.5 months following surgery, with an average of 36 months. One case of implant exposure was noted, with no other significant complications. Good motility of the prosthesis was noted in all cases. Conclusions: The quasi-integrated porous polyethylene orbital implant is safe to implant and provides good prosthetic motility without the need for pegs or screws. It was associated with an exposure rate similar to other commonly used implants following enucleation in retinoblastoma cases.

Targeting MDM2 and MDMX in Retinoblastoma

Retinoblastoma is the third most common form of cancer in infants, and metastatic retinoblastoma is lethal in approximately 90% of cases. Early detection and aggressive therapy has resulted in a 95% probability of survival for retinoblastoma patients in the United States. However, the United States only represents 3-4% of the retinoblastoma cases worldwide. The majority of children diagnosed with retinoblastoma each year live in developing countries where the probability of survival is closer to 50%. This difference in survival rates reflects poor early detection rates and limited resources for the aggressive therapy necessary to treat retinoblastoma and manage the side effects associated with broad-spectrum systemic chemotherapy in young children. In order to have the most significant impact on retinoblastoma treatment in the United States and worldwide, current efforts have focused on local delivery of targeted chemotherapy. In this review, we summarize recent data showing that the p53 pathway is inactivated in 75% of retinoblastoma patients due to extra copies of the MDM2 and MDMX genes. A small molecule inhibitor of MDM2 called nutlin-3 can induce p53-mediated cell death in retinoblastoma cells. Subconjunctival delivery of nutlin-3 in preclinical models of retinoblastoma confirmed the efficacy of this approach in vivo. The advantage of local application of targeted chemotherapeutic agents such as nutlin-3 is that greater intraocular drug concentrations can be achieved without the side effects associated with systemic broad-spectrum chemotherapy. We propose that subconjunctival administration of targeted chemotherapy may be the best treatment option for children with retinoblastoma in the United States and throughout the developing world because it provides greater tumor response without the costs and complications associated with current treatment protocols.

PRB detection as a common event in human retinoblastomas: An immunohistochemical study

Approximately 30% of the cases of retinoblastoma (RB), the childhood eye cancer, are inherited and are manifested by unilateral or bilateral tumor. In sporadic tumors, accounting for 70% of cases, only one eye is affected. RB has three histological features: undifferentiated anaplastic cells, retinoblast pattern, and differentiated pattern characterized by Flexner Wintersteiner rosettes (FWR). Currently, results concerning phosphoprotein RB (pRB) expression in RB tumors are contradictory. In this study we detected pRB immunohistochemically in 10 tumors from bilateral or unilateral RBs, which did not show gross chromosomal alterations in cytogenetic studies. Interestingly, pRB was undetectable in only one tumor where we found distinct histological features. Our results suggest that pRB immunopositivity may be common in these tumors. However, it does not rule out the possibility that pRB is functionally inactive in some cases. This may be due to the protein being present in phosphorylated form or being altered by point mutations not affecting its expression. Another possibility is that mechanisms other than RB1 gene changes may lead to retinoblastoma because not all cases of retinoblastoma show gene alterations. Together these findings may be useful in understanding the molecular mechanisms associated with this type of pediatric tumor.

Bilateral retinoblastoma: successful conservative treatment of both eyes

Abstract Purpose: Conservative treatment (focal therapy, local and systemic chemotherapy, radiotherapy) is today the standard in Retinoblastoma treatment. Preservation of both eyes is unfortunately, not always , possible. Methods: .From 1959 to 2007, 442 cases of retinoblastoma have been diagnosed and treated at the Retinoblastoma Referral Center of the University of Siena. 175 cases were bilateral. Results: 25 out of 175 bilateral cases have been conservatively treated. Age at diagnosis, sex, hereditary, stage at diagnosis (Reese Classification and ABC Classification), remission patterns and therapeutic protocol are reported. The age at diagnosis ranged from 4 days to 15 months (mean age: 5.4 months).8 out of 25 were females, 17 out 25 were males. 13 out of 25 were familial cases. Stage at diagnosis (50 eyes) was I in 16 eyes, II in 12 eyes, III in 8 eyes, IV in 11 eyes, V in 3 eyes. 25 out of 25 received chemotherapy and focal therapy according to the Italian protocol. 12 out of 25 relapsed. 9 out of 12 received new cycles of focal and chemotherapy. 2 out of 12 received also brachytherapy. In 2 out of 12 subconjuctival carboplatin has been used. In only 1 case (familial case)external radiotherapy was requested and the child died for a second tumor one year later. 5 out of 25 developed new foci, immediately treated only with focal therapy. Conclusions: The prognostic factors for successful conservative treatment are evaluated.

Demographics, clinical profile, management, and outcome of retinoblastoma in a tertiary care center in southern India

20011 Background: Retinoblastoma is the most common malignant intraocular tumor in children. The estimated incidence of retinoblastoma in India is about 2,000 a year. However, there is scant data on the clinical manifestations and outcome of retinoblastoma in India. Methods: In this retrospective case series, the medical records of 460 consecutive cases of retinoblastoma from January 1990 to December 2004 were analyzed for demographics, clinical profile, treatment and outcome (survival, organ and function salvage). Results: An integrated Ocular Oncology Service was established at the treatment center in the year 2000 and a specialized Children’s Eye Cancer Center was founded in 2004. The annual referral increased from &lt;20 a year before 2000 to 38 in 2000, and 120 in 2005. Two hundred and six (45%) patients were economically underprivileged. A majority (303, 66%) presented &lt;3 years of age. There were 277 (60%) males. Although 188 (41%) were bilateral, family history was forthcoming in only 19 (4%). Of 648 involved eyes, 531 (82%) eyes were symptomatic. Leucocoria (71%) was the most common symptom, followed by visual loss (12%), eyelid edema or proptosis (7%), squint (6%), pain (2%), redness (2%), enlarged eyeball (2%), or shrunken eyeball (1%). The tumor was intraocular in 609 (94%) eyes while 39 (6%) were extraocular. Enucleation was the most common primary treatment for intraocular retinoblastoma (236 of 451, 52%), followed by chemoreduction coupled with focal therapy (26%), focal therapy alone (11%), external beam radiation (55) or chemotherapy alone (4%). Histopathologic risk factors predictive of metastasis were found in 152 of 277 (55%) eyes that underwent enucleation. Chemoreduction with focal therapy resulted in eye and vision salvage in 109 of 118 (92%). At the final follow-up (minimum 24 months), 434 (94%) were alive and well. Conclusions: Retinoblastoma has excellent prognosis for survival, eye salvage and vision salvage with the current management modalities. An integrated approach involving a team of a pediatric oncologist and an ocular oncologist at a comprehensive tertiary care center may augment referrals and help implement systematic treatment strategies. No significant financial relationships to disclose.

Study on the risk factors for optic nerve invasion in 381 cases of retinoblastoma

To investigate the clinical and pathologic outcomes of a large group of retinoblastoma (RB) cases to ascertain the risk factors of RB optic nerve invasion. In this paper, we summarized the clinical and pathologic data of 381 retinoblastoma cases in Beijing Tongren Hospital observed from 1990 to 2002. Statistical analyses were performed on the sex, age, unilateral or bilateral cases, length of symptoms, clinical situation, stage, histological type and the degree of optic nerve invasion. The degree of RB optic nerve invasion was closely correlated to clinical stage and tumor differentiation. Avoiding the risk factors of RB optic nerve invasion is very important for the prognosis of RB.