Long Term Follow-up Results of External Beam Radiotherapy as Primary Treatment for Retinoblastoma

The authors reviewed their experiences of external beam radiotherapy (EBR) as an initial treatment in retinoblastoma patients to determine its long-term effect on subsequent tumor control and complications. A total of 32 eyes in 25 patients that underwent EBR for retinoblastoma were reviewed retrospectively. The patients consisted of 21 boys and 4 girls of median age at treatment of 7.1 months. Radiation doses ranged from 35 to 59.4 Gy. The 10-yr ocular and patient survivals were 75.4% and 92.3%, respectively. Nine of the 32 eyes progressed; 7 of these were enucleated and 2 were salvaged by focal treatment. According to the Reese-Ellsworth classification, 4 of 5 eyes of Group II, 13 of 16 Group III eyes, 2 of 4 Group IV eyes, and 5 of 7 Group V eyes were retained, and of the 32 eyes, 13 had visual acuity better than 20/200. Eleven patients experienced a radiation-induced complication. No patient developed a second malignancy during follow-up. Despite the limited number of patients enrolled, EBR may provide a mean of preserving eyeball and vision for some advanced lesions.

Bilateral retinoblastoma: Long-term follow-up results from a single institution / 소아과

PURPOSE: The authors aimed to analyze the long-term effects of treatments, especially external beam radiotherapy (EBRT), in bilateral retinoblastoma patients. METHODS: This retrospective study analyzed the medical records of 22 bilateral retinoblastoma patients who were registered between October, 1987 and October, 1998 and followed-up for more than 10 years. They were treated by enucleation, EBRT, and systemic chemotherapy. Age at diagnosis, sex, delay prior to treatment, Reese-Ellsworth (RE) classification, and the local treatment modalities were analyzed in relation to recurrence-free survival (RFS) and complications. RESULTS: Median age at diagnosis was 7.0 months (range 1.7-31.6 months). Leukocoria was the most common presenting feature. Two patients had a familial history. The RE classifications of the 44 eyes were group II in 4, III in 14, IV in 4, and V in 22. At the end of a median follow-up period of 141 months (range 55-218 months), 20 patients were alive. The 10-year ocular survival rate of the 44 eyes was 56.8+/-7.5%. The 10-year RFS and ocular survival rate of the 29 eyes treated by combined EBRT and chemotherapy were 75.9% and 86.2%, respectively. Treatment delay (>3 months) was found to be related to higher risk of recurrence. Complications after EBRT were cataract, retinal detachment, phthisis bulbi, and facial asymmetry. No patient developed a second malignancy during the follow-up period. CONCLUSION: Early detection and prompt treatment can increase ocular survival rates. In addition, careful attention should be paid to possible long-term sequelae in these patients.

A Case of the Ciliary Body Neurilenioma

We experienced a case of the ciliary body neurilemorna in a 26 year old m.an who had progressive visual loss and ocular pain for two years. Neurilemomas are benign tumors and rarely occur within the eyeball. The clinical apearance of the lesion was similar to that presened by choroidal melanoma, therefore they are misdiagnosed as malignant melanoinas, resulting in enucleation. We reviewed the literature on solitary neurilemoma of the uveal tract and analyzed the main clinical and pathological features of the uveal neurilem.oma with this case which successfully treated by iridocyclectomy.

Treatment and Prognosis of Retinoblastoma: Clinicopathologic Analysis of 101 Cases

The clinicopathologic characteristics, treatments and prognosis of retinoblastoma, the most common intraocular tumor in children, were studied retrospectively in 101 cases(128eyes) who visited our clinic from 1987 to 1996. All patients were followed for 2 years or longer. Twenty seven cases were bilateral and seventy four cases were unilateral,. Eihgty four eyes were enucleated. Twenty one eyes were successfully treated by conservative modality. The rest refused any type of treatment. Orbital recurrence or distant metastasis were observed in 5 cases after enucleation without systemic treatment, and one died in spite of irradiation and aggressive chemotherapy. It is widely recognized that the prognosis for survival of retinoblastoma patients, especially unilateral, is excellent, however the authors emphasize the importance of careful postoperative histopathologic review and long term periodic follow-up to improve long-term prognosis.

Deletion of Rb1 gene in late osteosarcoma from survivor of unilateral retinoblastoma: a case report

It has been well known that the survivors of retinoblastoma are prone to have osteosarcoma. But the secondary tumor usually occurs in bilateral, hereditary type of retinoblastoma. We report one case of osteosarcoma in a survivor of unilateral, sporadic retinoblastoma. A fourteen year old male presented with a painfully swollen distal forearm of 2 month duration. He had enucleated his left eye 10 years ago due to retinoblastoma with no other adjuvant therapy. We managed him with our conventional protocol and identified deletion of Rb gene from his pathological specimen by using the PCR-RFLP method. This result is unusual for unilateral nonhereditable retinoblastoma and may suggest gene level change even in sporadic cases. And Rb gene study may be helpful for unilateral, sporadic retinoblastoma patient in detecting the possibility of late osteosarcoma.

Enhancement of Cytotoxicity of Chemotherapeutic Agents by Buthionine sulfoximine in Retinoblastoma Cell Line

This study was performed to evaluate in vitro cytotoxicity of chemotherapeutic agents in established human retinoblastoma cell line, Y79 and to study the possibility of enhancing the cytotoxicity of chemotherapeutic agents by administration of buthionine sulfoximine(BSO) which lowers the intracellular glutathione(GSH) level. IC50 defined as the concentration which inhibits the cell survival rates to 50% compared with control group was used to evaluate cytotoxicity. Intracellular level after 13.50 adminstration were measured and compared with the level prior to administration of BSO. Doxorubicin, cisplatin, and melphalan showed significant decrease of IC50 by administration of BSO(p0.05). Intracellular GSH level prior to the administration of BSO was 0.931nM/mg protein. After the administration of BSO, they were lowered to 0.095nM/mg protein in both BSO concentrations. Results listed above suggest that cytotoxicity of doxorubicin, cisplatin, and melphalan can be enhanced by ESO. This effect may be mediated by decreased intracellualr level of GSH by BSO.

Expression of urokinase: type plasminogen activator, its receptor, and its inhibitor in gastric adenocarcinoma tissues

The plasminogen and plasmin system, which is mainly regulated by urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1), is generally believed to play a role in cancer invasion and metastasis. This study was conducted to investigate the role of uPA, uPAR and PAI-1 in the invasion and metastasis of gastric adenocarcinoma. The expression of mRNAs for uPA and PAI-1 was determined by Northern blot analysis in nine primary gastric cancer tissues, nine paired metastatic lymph nodes and normal gastric mucosa. The mRNA of uPA was not or faintly detected in normal mucosa, while the expression was increased in both primary gastric cancer tissues and metastatic lymph nodes to a similar degree. The mRNA expression for PAI-1 in the gastric cancer tissues was not different from that in the paired metastatic lymph nodes and normal mucosae. uPAR was determined by immunohistochemical staining, demonstrating that five (56%) and six (67%) out of nine primary gastric cancer tissues and nine paired metastatic lymph nodes were positive, respectively and the intensity was stronger in metastatic lymph nodes. The results support the concept that most gastric cancer cells may have an innately moderate level of uPA and uPAR, and that increase of uPAR expression can be considered to be closely associated with cancer invasion and metastasis.

Ocular manifestations of systemic tuberculosis: Report of 3 cases

Tuberculosis is a chronic infectious disease caused by mycobacteria species, which can affect any organ of the body including the eye. Primary ocular tuberculosis is very rare condition and likely to be caused by introduction of bacilli through epithelial injury. Post primary infections (or secondary infection) due to direct hematogenous spread or contiguous spread from an adjacent structure are more common presentations of ocular tuberculosis. The authors experienced 3 cases of ocular tuberculosis associated with systemic infection. One case was a scleral involvement of miliary tuberculosis and the others were choroidal tuberculoma from systemic tuberculosis.

Four Families of Hereditary Retinoblastoma

We analysed the clinical findings in four families of hereditary retinoblastoma. All four children with retinoblastoma were male. Two of them were diagnosed after two years of age and the remainder were before seven months of age. The relatives affected with retinoblastoma were one father, one mother, one sibling, and one second cousin of patients respectively. To our knowledge, this is the first report of hereditary retinoblastoma with family history in Korea.

A Case of Osteosarcoma Developed in a Patient of Untreated Bilateral Retinoblastoma

Retinoblastoma is one of the primary malignant tumors which rarely undergo spontaneous regression. Survival rate from retinoblastoma is in excess of 90%, but the subsequent development of second tumor is an important factor of the long-term prognosis. The authors experienced a case of osteosarcoma developed on left distal femur in a patient of bilateral retinoblastoma which underwent spontaneous regression.

A Clinicopathologic Study of 46 Cases of Eyelid Malignancy

We studied retrospectively 46 patients of primary malignant eyelid tumors who were histologically diagnosed in Korea Cancer Center Hospital from May, 1987 to December, 1994 and followed for 6 months or longer. 46 patients consist of, 22 cases of basal cell carcinoma(47.8%), 10 cases of squamous cell carcinoma(21.7%), 9 cases of sebaceous gland carcinoma(19.6%), and 5 cases of malignant melanoma(10.9%). Our modalities of treatment for eyelid malignancy included excision under frozen-section control, radiotherapy and cryotherapy. In case of regional lymph node metastasis we performed radiation treatment with or without excision of primary tumor and regional lymph node dissection. A case with distant metastasis underwent radiotherapy combined with chemotherapy. Following initial treatment, 4 cases showed recurrence and 3 cases developed regional or distant metastasis. In this study, we emphasize that suspected eyelid malignancy should be histologically diagnosed with biopsy and treated adequately at an early stage to reduce recurrence or metastasis.

Clinical Analysis of Retinoblastoma

We analyzed retrospectively 58 patinets of retinoblastoma for the first, ocular symptoms, gender, family history, funduscopic findings, treatment modalities and results from 1987 to 1993. Fourteen patients were bilateral, forth-four were unilateral, and seventy-two eyes were affected in sum. The average of age of the patients was 25.6 months. Their first ocular symptoms were leukocoria, squint and etc. Three patients were suspected as familial type of retinoblastoma. We claasified the patients according to the affected degree of the retina;over three-fourths of the retina was affected in 34 eyes. We treated them with enucleation, radiation, chemotherapy, episcleral plaque radiotherapy, laser photocoagulation and cryotherapy. After these treatments, orbital recurrence was observed in one case and among the ten eyes treated with eye-conserving treatments, nine eyes are maintained with periodic examination under general anesthesia and the treatment of laser photocoagulation and cryotherapy until now.

Loss of retinoblastoma gene and amplification of N-myc gene in retinoblastoma

We have analyzed paired samples of genomic DNA from peripheral leukocyte and primary tumor tissue from nine patients with retinoblastoma (RB) and from two RB cell lines, WERI-Rb-1 and Y79, to detect the molecular alterations of the retinoblastoma susceptibility gene (RB-1) and N-myc gene. In Southern analysis, RB-1 deletions in tumor tissues were detected in five patients (56%), one of these revealed a total loss of RB-1. N-myc amplification was found only in one (11.1%) out of nine patients. We also observed a total loss of RB-1 in WERI-Rb-1, and a more than 100-fold amplification of N-myc in Y79. The analysis of the relationship between molecular events and clinical characteristics such as age, sex, tumor laterality did not reveal any specific correlation. These results suggest that genetic backgrounds of RB in Korean patients are quite similar to those of reported cases elsewhere. The high sensitivity of our method in detecting the RB-1 loss indicates that this method can be a useful tool for initially screening a large number of tumors.

Chemosensitization to adriamycin by cyclosporin A and verapamil in human retinoblastoma cell lines

The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were investigated using MTT assay against two human retinoblastoma cell lines, Y79 and WERI-Rb-1. Y79 and WERI-Rb-1 were totally resistant to doses up to 5.0 micrograms/ml of verapamil. Cyclosporin A inhibited the survival of Y79 and WERI-Rb-1 dose-dependently, however, the maximum inhibition at the highest concentration tested (5.0 micrograms/ml) was less than 50% (% survival at 5.0 micrograms/ml of cyclosporin A: 65.6% and 66.9% in Y79 and WERI-Rb-1, respectively). Combination of cyclosporin A and verapamil did not further inhibit the survival of Y79 and WERI-Rb-1 compared with cyclosporin A alone. Adramycin inhibited the survival of Y79 and WERI-Rb-1 dose-dependently. The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were evaluated in terms of sensitizing index (SI: the ratio of IC50 to adriamycin alone to IC50 to adriamycin in the presence of cyclosporin A and/or verapamil). Cyclosporin A significantly enhanced SI and the addition of verapamil enhanced SI further: SI values at 5.0 micrograms/ml of cyclosporin A, 5.0 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of verapamil, 5.0 micrograms/ml of cyclosporin A plus 3.0 micrograms/ml of verapamil were 2.0, 2.6 and 2.8 in Y79 and 2.6, 5.8 and 9.7 in WERI-Rb-1, respectively. These results suggest that cyclosporin A and verapamil are promising chemosensitizers to adriamycin in the treatment of retinoblastoma.