Non conventional treatment of human hydatidosis

BACKGROUND: Combined modality therapy in the treatment of retinoblastoma may decrease treatment-related morbidity and second tumor-associated mortality, while maintaining excellent tumor control rates. OBJECTIVE: To evaluate tumor control and potential synergy between intravitreally delivered carboplatin and external beam radiation therapy (EBRT), using a transgenic murine model of spontaneous heritable retinoblastoma. METHODS: Sixty-six mouse eyes from 4-week-old transgenic mice positive for the simian virus 40 large T antigen were evaluated. Thirty-three mice were treated with 5 intravitreal injections of carboplatin (ranging from 0.1-4.0 micrograms) combined with concurrent bilateral EBRT (ranging from 10-30 Gy) delivered in twice daily 5-Gy fractions. All eyes were followed up for treatment complications. Twelve weeks following final treatment, all eyes were enucleated, serial histologic sections obtained, and the eyes examined for the presence of retinoblastoma. RESULTS: No eye treated with 0.1 microgram of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 microgram of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 microgram of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 micrograms of carboplatin in combination with EBRT had complete tumor control. The chemotherapeutic enhancement ratio ranged from 1.07 to 3.24. CONCLUSIONS: Combined administration of intravitreal carboplatin and EBRT enhances local tumor control in murine retinoblastoma. Combining these treatment modalities may allow tumor control in selected patients with retinoblastoma while decreasing treatment-related morbidity and the mutagenic risks associated with radiation and systemic chemotherapy.     

Unilateral retinoblastoma: new intraocular tumours after treatment

A retrospective chart review of 427 eyes diagnosed with unilateral retinoblastoma was performed to determine which eyes, which patients, and when new intraocular tumours would develop after treatment. Mean follow up was 8.16 years. Twenty five (6%) of 427 unilateral retinoblastoma patients developed new intraocular tumours after treatment. Five (1%) unilateral patients who were previously treated with enucleation developed new tumours (in the fellow eye). Fifteen (24%) unilateral patients who were previously treated with external beam radiation developed new tumours (equally in either eye). New tumours did not develop in the macula of either eye. The relative risk of developing new intraocular tumours after treatment was 16% in patients diagnosed before 1 year old and 2.2% for patients diagnosed after 1 year old (p < 0.001). The mean time to onset for the development of new tumours after treatment was 0.74 years; no new tumours appeared after 7.5 years of age. Those patients who are diagnosed with unilateral retinoblastoma in the first 6 months of life and have a family history of the disease are at greatest risk of developing new intraocular tumours.     

Recent developments in the management of retinoblastoma

The management of retinoblastoma has gradually changed over the past few decades. There is a trend away from enucleation and external beam radiotherapy toward focal conservative treatments. This is primarily because of earlier detection of the disease and more focused treatment modalities. Enucleation is still employed for retinoblastoma that fills most of the eye, especially when there is a concern for tumor invasion into the optic nerve or choroid. After enucleation, an integrated orbital implant, provides improved motility and appearance of the prosthesis. External beam radiotherapy continues to be an important method of treating less advanced retinoblastoma, especially when there is diffuse vitreous or subretinal seeding. Plaque radiotherapy is useful for controlling small- to medium-sized retinoblastomas, even those with focal vitreous seeds. Tumors that recur after failure of other methods are often suitable for plaque treatment. When plaque radiotherapy is employed in a child receiving chemotherapy, eventual radiation retinopathy can occur. Cryotherapy and photocoagulation provide excellent control of selected small tumors. Advanced laser delivery systems, particularly those that have been adapted to the indirect ophthalmoscope, have facilitated the visualization for treatment of tumors. Thermotherapy is the newest focal method for retinoblastoma. When combined with chemotherapy, thermotherapy provides satisfactory tumor control, leaving the child with a reasonably small scar, thus preserving more vision. Chemoreduction, using intravenous or subconjunctival routes, is often employed to reduce initial tumor volume and thus allow for focal treatment to eradicate the residual smaller tumor. Many children with advanced retinoblastoma can be spared external beam radiotherapy and enucleation mostly as a result of chemoreduction and focal methods. Chemoreduction combined with cryotherapy, thermotherapy, and plaque radiotherapy plays an important role in the current management of many children with retinoblastoma.     

Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85-31). Radiation Therapy Oncology Group

PURPOSE: To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation vs. radiation alone on a group of pathologically staged lymph node-positive patients with adenocarcinoma of the prostate. METHODS AND MATERIALS: A national prospective randomized trial (RTOG 85-31) of standard external beam irradiation plus immediate androgen suppression vs. external beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy-three of the patients in this trial had biopsy-proven pathologically involved lymph nodes. Ninety-eight of these patients received radiation plus the immediate androgen suppression (LHRH agonist), while 75 received radiation alone with hormonal manipulation instituted at the time of relapse. RESULTS: With a median followup of 4.9 years, estimated progression-free survival with PSA < 1.5 ng/ml at 5 years was 55% for the patients who received radiation plus immediate LHRH agonist vs. 11% of the patients who received radiation alone with hormonal manipulation at relapse (p = 0.0001). Because all of these patients had locally advanced disease (i.e., pathologically positive lymph nodes), stage does not explain this difference in outcome, and Gleason grade was not statistically different between the two groups. Estimated absolute survival at 5 years for the radiation and LHRH group was 73 vs. 65% for the radiation alone group who received androgen suppression at relapse. Estimated disease-specific survival at 5 years was 82% for the radiation and immediate LHRH agonist group and 77% for the radiation-alone group. CONCLUSION: Patients with adenocarcinoma of the prostate and pathologically involved pelvic lymph nodes (pN+ or clinical stage D1) should be seriously considered for external beam irradiation plus immediate hormonal manipulation over radiation alone with hormonal manipulation at the time of relapse.     

Multidrug resistance protein (MRP) expression in retinoblastoma correlates with the rare failure of chemotherapy despite cyclosporine for reversal of P-glycoprotein

Failure of chemotherapy associated with expression of the multidrug resistance protein p170 frequently occurs in retinoblastoma (RB). Despite using cyclosporine, which inhibits p170 and improves our chemotherapy results, rare failures occur. In nonmetastatic primarily enucleated RBs, we show expression of p170 in 3 of 18 samples and expression of multidrug resistance protein (MRP), the second protein associated with resistance to chemotherapy, in 1 of 18 samples. All three RBs that failed chemotherapy without cyclosporine expressed MRP with p170. All three RBs that were enucleated immediately when chemotherapy failed despite the addition of cyclosporine expressed only MRP. One RB enucleated 2 years after failing chemotherapy with cyclosporine, despite radiation and salvage chemotherapy, expressed both p170 and MRP. Two metastatic RBs that expressed both p170 and MRP at diagnosis and at recurrence failed chemotherapy without cyclosporine, whereas one metastatic RB that expressed neither protein was cured by chemotherapy without cyclosporine. MRP may result in failure of chemotherapy despite the elimination of p170-expressing clones by cyclosporine.     

Rubeosis iridis in retinoblastoma. Histologic findings and the possible role of vascular endothelial growth factor in its induction

PURPOSE: Iris neovascularization (rubeosis iridis) is a common finding in eyes harboring retinoblastoma. The purpose of the current study is to evaluate the histologic factors that may affect the development of rubeosis iridis in eyes with retinoblastoma and to examine whether vascular endothelial growth factor (VEGF), a hypoxia-induced angiogenic factor, is produced by hypoxic retinoblastoma and retinal cells in these eyes. MATERIALS AND METHODS: One hundred eighty-one enucleated eyes containing retinoblastoma were the source for the current study. Histologic slides were evaluated for the presence and degree of rubeosis iridis as well as for other histologic factors. Univariate and multivariate statistical analyses were performed to find a correlation between rubeosis iridis and the other histologic factors. Eight of the eyes underwent in situ hybridization with a specific VEGF mRNA probe to locate tumor and retinal cells that may produce this hypoxia-induced angiogenic factor. RESULTS: The amount of tumor necrosis as well as choroidal and optic nerve invasion was found to be one of the most important factors that correlated with the presence and degree of rubeosis iridis in the examined eyes. All eight eyes that underwent in situ hybridization analysis showed strong signals of VEGF mRNA in retinoblastoma cells around necrotic regions and in the outer nuclear layers in areas of detached retina. CONCLUSIONS: There exists an association between rubeosis iridis and histologic factors found in advanced stages of retinoblastoma, especially the amount of tumor necrosis. Vascular endothelial growth factor may well be an angiogenic factor that is secreted by the hypoxic retinoblastoma and retinal cells and, reaching the iris, causes (presumably in collaboration with other factors) rubeosis iridis.     

Postoperative radiation for cervical cancer with pathologic risk factors

PURPOSE: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. METHODS AND MATERIALS: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidently at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. RESULTS: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced Grade 2 or 3 late treatment- related complications. No patient in either group had Grade 4 or 5 complications. Pathologic risk factors were analyzed. Lymph node positivity and lymphovascular space invasion were found to be significant (p = 0.01 and p = 0.02). Positive margins, deep invasion, and age were not significant. CONCLUSION: Our results demonstrate the efficacy of postoperative irradiation for cervical cancer with pathologic risk factors. Overall, the local control rate was 89.5% The HDR results demonstrate that this method can be delivered safely and effectively.     

Treatment of oesophageal carcinoma at a small rural hospital

OBJECTIVE: For the primary treatment of pseudophakic retinal detachment, vitrectomy could be preferred to episcleral buckle because it does not induce myopia, it clears opacities of the posterior capsule and/or of the vitreous and allows a good visualization of the fundus. This study was determined to compare the anatomic and functional results of vitrectomy and episcleral buckle. METHODS: from 1990 to 1995, 93 pseudophakic eyes were operated on for retinal detachment. 75 eyes were treated with episcleral buckle (group I) and 18 eyes were treated with vitrectomy (group II). In the latter group, 4 eyes had a giant tear, and 4 other eyes had a macular hole associated with high myopia. The anatomic and functional results were analyzed retrospectively. RESULTS: The retina was reattached with one operation in 67 eyes of group I (89%) and 16 of group II (89%). More than one month after the first operation, the retina redetached in 6 eyes of Group I (8%) and one eye of group II (6%). The causes of failure were a) new or missed retinal tears [Group I: 10 eyes (13%), group II: 3 eyes (17%)] and b) vitreoretinal proliferation (group I: 4 eyes, group II: 0). The number of subsequent reoperations for failures or recurrences was higher in group I than in group II. At the final examination, the retina was attached in 73 eyes of group I (97%) and in 18 eyes of group II (100%). The Kruskal-Wallis test did not detect any difference between the two groups concerning the pre- or postoperative visual acuities. CONCLUSION: Vitrectomy seems as effective as episcleral buckle for the treatment of pseudophakic retinal detachment and offers additional advantages.     

Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation

Chemotherapy without radiation has not controlled most intraocular retinoblastoma, perhaps because of the common high expression of multidrug resistance P-glycoprotein that we found in retinoblastoma. Cyclosporin blocks P-glycoprotein-induced efflux of vincristine and teniposide in vitro, and possibly modulates responses to carboplatin. To avoid eye irradiation in bilateral retinoblastoma patients with RB1 germline mutations, which incurs a high second malignancy rate, we added cyclosporin A to a vincristine-teniposide-carboplatin protocol and consolidated chemotherapy responses with focal therapy. We scored patients requiring irradiation, enucleation, or focal ablation of central vision as failures. In 21 study patients, the overall relapse-free rate at a median follow-up of 3.3 years was 76%, with a rate of 92% for newly diagnosed and 50% for previously treated, relapsed retinoblastoma. Our results for the most unfavorable tumors with vitreous seeds (86% at 3.5 years) are better than published success rates of irradiation for similar tumors, or irradiation with the same chemotherapy without cyclosporin (45% at 2. 6 years). These results also exceeded our historic success rate with similar chemotherapy without cyclosporin, focal therapy, and/or radiation in 19 equivalently poor-risk patients (relapse-free rate 37% at a median follow-up of 5.6 years, P = 0.032), 16 of whom were previously untreated (relapse-free rate also 37%, P = 0.012). A better outcome occurred with higher cyclosporin blood levels and projected tissue exposure. Cyclosporin did not enhance the usual chemotoxicity. This clinical study suggests that cyclosporin improves the long-term response of retinoblastoma to chemotherapy, possibly by more than one mechanism.     

Intraocular silicone oil tamponade. A clinico-pathologic study of 36 enucleated eyes

BACKGROUND: Previous histological studies have shown that intraocular silicone oil induces irreversible changes in ocular tissues, especially the retina. The purpose of this study was to analyze, in a larger group of enucleated eyes, changes in intraocular tissue after silicone oil injection, dependent on intraocular pressure, how long the oil was in the eye, and the viscosity of intraocular silicone oil. PATIENTS AND METHODS: We did histological examinations on 36 enucleated globes with intraocular silicone oil after vitreoretinal surgery and compared them with 68 enucleated globes treated with buckle and encircling band using immunohistochemistry (n = 5) and electron microscopy (n = 7). For statistical evaluation we used the chi(2) test and analysis of variance. RESULTS: After silicone oil injection we observed a more pronounced reduction in corneal endothelial cells (58%), more frequent closed chamber angle (86%), atrophy of the ciliary body (80%) (P < 0.05), proliferative vitreoretinopathy (89%), and glaucomatous atrophy of the optic nerve (56%) (P < 0.01). The retinae showed independent of the use of silicone oil a loss of inner and outer segments of photoreceptors and of ganglion cells and thinning and rareficaton of all other retinal layers. Globes with silicone oil revealed vacuoles both free and incorporated by macrophages in all layers of the retina. Similar vacuoles were seen in the optic nerve, choroid, retinal pigment epithelium, ciliary body, iris, chamber angle and the corneal endothelium. Silicone oil vacuoles were seen in the retina and optic nerve by 1 month after surgery in two eyes with high intraocular pressure (42 mmHg). Six of eight eyes with normal intraocular pressure levels showed retinal vacuoles, 3 of them after 2 months. Vacuoles in the optic nerve were found in eight of nine eyes with intraocular instillation of 1000 mPa silicone oil. There was no clinicohistopathological correlation between the presence of vacuoles in the retina or optic nerve and the duration and viscosity of intraocular silicone oil. CONCLUSIONS: This study suggests that vacuoles in eyes with silicone oil instillation can be found in the retina after 4 weeks. The period of intraocular silicone oil should be limited to 3-6 months.     

Toxicity and dose-response studies of 1,25-(OH)2-16-ene-23-yne vitamin D3 in transgenic mice

The vitamin D3 analogue 1,25-(OH)2-16-ene-23-yne vitamin D3 (16,23-D3) in doses with low systemic toxicity has been demonstrated to inhibit retinoblastoma growth in transgenic mice. This study examines the dose-dependent response for inhibition of tumor growth in transgenic mice with retinoblastoma and evaluates the in vivo toxicity of 16,23-D3 in nontransgenic mice. Transgenic 8-10-week-old mice with retinoblastoma (n = 119) were randomly assigned to groups receiving 1.0, 0.75, 0.5, 0.35, 0.2, or 0.05 microg of 16,23-D3 and a vehicle alone (control) group i.p. five times a week for 5 weeks. An additional control group received no injection. Eyes were enucleated one week after the end of treatment, and tumor areas were measured. To determine the toxic dose, transgene-negative littermates received 0.5, 1.0, 1.5, 2.5, 3.5, 4.5, or 5.0 microg of 16,23-D3, and control groups received vehicle alone, 5 days a week for 5 weeks. Serum calcium levels were measured, and necropsies were performed on animals from each group. In the dose-response study, tumor growth inhibition was greatest in the group receiving 0.35 microg (55% inhibition; P = 0.0056) and was also significant in the group receiving 0.5 microg (42% inhibition; P = 0.036). The systemic toxic effects due to hypercalcemia occurred at doses of > or =1.0 microg. 16,23-D3 inhibits tumor growth at doses > or =0.35 microg and shows toxic effects at doses > or =1.0 microg related to hypercalcemia in mice fed an unrestricted diet. No toxicity was observed with lower doses.     

The effect of radial keratotomy on ocular integrity in an animal model

The safety of deep corneal incisions in radial keratotomy was evaluated in a porcine model of blunt trauma. One eye of each enucleated pair (right and left) of porcine eyes was subjected to a variation of radial keratotomy; the fellow eyes served as unoperated-on controls. All eyes were subjected to a standard injury. Control eyes ruptured at the equatorial sclera. Eyes with radial incisions cut through approximately 70% of corneal thickness also ruptured at the equator. When incisions of this depth (70%) were extended across the limbus (rather than to the corneal-scleral junction), all ruptures occurred at the limbal incisions. Eyes cut 95% to 100% of corneal thickness tended to rupture at the incisions. The safety of deep radial keratotomy incisions with respect to ocular integrity is discussed.     

Soft tissue sarcomas: preoperative versus postoperative radiotherapy

External beam radiation may be given either before or after excision of a primary soft tissue sarcoma. This study was undertaken to determine whether or not the timing of radiotherapy was associated with any difference in either local control, survival, or incidence of complications. The files of 112 patients with a primary, nonmetastatic, extremity soft tissue sarcoma, treated with limb salvage surgery and irradiation were evaluated. Data regarding tumor stage, grade, site, surgical margin, dosage and timing of radiotherapy, treatment complications, disease relapse, and relapse-free survival (RFS) were analyzed. Kaplan-Meier lifetable analysis was used to determine survival estimates. There was no significant difference in the 5-year RFS between patients receiving radiotherapy (RT) preoperatively versus postoperatively; 56 +/- 15% and 67 +/- 12% (P = 0.12, Mantel-Cox), respectively. There was no significant difference in the overall survival between patients receiving RT preoperatively versus postoperatively; 75 +/- 15% and 79 +/- 11% (P = 0.94), respectively. Actuarial local control at 5 years for preoperative versus postoperative RT patients was not statistically different; 83 +/- 12% versus 91 +/- 8% (P = 0.41), respectively. Wound complications were more frequent in preoperative RT patients (31%) compared to postoperative RT patients (8%) (P = 0.0014, chi-square). Preoperative irradiation was not associated with any benefit in terms of relapse-free survival, overall survival or actuarial local control in this series. A higher incidence of major wound complications was found among patients treated with preoperative irradiation. We recommend that patients with a resectable extremity soft tissue sarcoma be treated with postoperative irradiation, reserving preoperative irradiation for those situations in which either the tumor is initially thought to be unresectable or the original tumor boundaries are obscured.     

External beam radiation in patients suffering from exudative age-related macular degeneration. A matched-pairs study and 1-year clinical follow-up

BACKGROUND: The aim of this prospective study was to ascertain whether external beam irradiation is effective in patients with subretinal neovascularization (SRN) due to age-related macular degeneration (AMD). METHODS: All patients had subfoveal SRN due to AMD as verified by fluoresceinangiography. Two hundred and eighty-seven patient-eyes were treated by external beam irradiation (total dose of 16 Gy in 2-Gy fractions, 5 times a week) from January 1996. The analysis was restricted to those 73 patients with a minimum follow-up of 11 months. Eighteen patients with subfoveal SRN who refused treatment served as control group (CG). 18 patients of the treatment group (TG) were matched for visual acuity, refraction and extent of SRN. The statistical analysis was performed with the unpaired t-test. RESULTS: The mean age of the CG was 73.9 years (range 66.9-81.3 years) and of the TG 75.6 years (range: 65.7-80.6 years). The median follow-up was 13.5 months (range 11.9-18.4 months) in the CG and 12.9 months (range 11-13.9 months) in the TG. The initial visual acuity (VA) was 20/80 in both groups. After 7 months the follow-up revealed median VA of 20/400 in the CG and 20/160 in the TG (P=0.0335). The final median VA was 20/400 in both groups, with a range from 20/40 to 20/1000 in the CG and from 20/63 to 20/500 in the TG (P=0.2433). The SRN doubled in size during this time in both groups. CONCLUSION: These results suggest that external beam irradiation applied in 2-Gy fractions 5 times a week slows down the visual loss in exudative AMD for a short time. Nevertheless, the patients' reading vision could not be saved in the long term.     

Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma

BACKGROUND: The authors report observed 10-year brachytherapy results in the treatment of 152 consecutive patients with clinically organ-confined prostate carcinoma. METHODS: One hundred and fifty-two consecutive patients with T1-T3, low to high Gleason grade, prostate carcinoma were treated between January 1987 and June 1988 at Northwest Hospital in Seattle, Washington. Their median age was 70 years (range, 53-92 years). Of these 152 patients, 98 (64%) received an iodine-125 implant alone (Group 1), and the remaining 54 patients (36%), who were judged to have a higher risk of extraprostatic extension, also were treated with 45 gray (Gy) of external beam irradiation to the pelvis (Group 2). No patient underwent lymph node sampling, and none received androgen ablation therapy. Multivariate regression and the Mann-Whitney rank sum test were used for statistical analysis. Preoperative patient data with associated success or failure outcomes at 10 years after treatment were used for training and validating a back-propagation neural network prediction program. RESULTS: The average preoperative prostate specific antigen (PSA) value, clinical stage, and Gleason grade were 11.0 ng/mL, T2, and 5, respectively. The median posttreatment follow-up was 119 months (range, 3-134 months). Overall survival 10 years after treatment was 65%. At last follow-up only 3 of the 152 patients (2%) had died of prostate carcinoma. Ninety-seven patients (64%) remained clinically and biochemically free of disease at 10 years of follow-up and had an average PSA value of 0.18 ng/mL (range, 0.01-0.5 ng/mL). In these patients a period of 42 months was required to reach the average PSA (0.5 ng/mL). The median to last PSA follow-up was 95 months (range, 3-134 months). Postoperative needle biopsies were negative in 56% of patients, positive in 15% of patients, and not available in 29% of patients. Only 6% of patients developed bone metastasis. At 10 years there was no statistically significant difference in treatment outcome between patients who received iodine-125 alone, and those who received iodine-125 with 45-Gy external beam irradiation (P = 0.08). Nevertheless, in these two groups preoperative PSA, stage, and Gleason grade were significantly different (P < 0.01). In the artificial neural network analysis, pretreatment serum PSA was the most accurate predictor of disease-free survival. CONCLUSIONS: Percutaneous prostate brachytherapy is a valid and efficient option for treating patients with clinically organ-confined, low to high Gleason grade, prostate carcinoma. Observed 10-year follow-up documents serum PSA levels superior to those reported in several published external beam irradiation series, and comparable to those published in a number of published radical prostatectomy series.     

Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma

BACKGROUND/AIMS: A checkpoint mechanism in late G1, whose regulation via loss of retinoblastoma protein (pRB) or p16, or overexpression of cyclin D1 or cyclin dependent kinase 4 (CDK4), has been proposed to constitute a common pathway to malignancy. The aims of this study were (a) to compare markers of cell cycle G1-S phase transition in an intraocular tumour with known pRB deficiency (retinoblastoma) and compare it with one with an apparently functional pRB (uveal melanoma); (b) to determine if one of these markers may have a role in the pathogenesis of uveal melanoma; and (c) to determine if there is a difference in cell cycle marker expression following treatment of uveal melanoma and retinoblastoma. METHODS: 90 eyes were enucleated from 89 patients for retinoblastoma (n = 24) or for choroidal or ciliary body melanoma (n = 66). Conventional paraffin sections were assessed for cell type and degree of differentiation. Additional slides were investigated applying standard immunohistochemical methods with antibodies specific for cyclin D1 protein, pRB, p53, p21, p16, BCL-2, and MIB-1. RESULTS: Cyclin D1 protein and pRB were negative in retinoblastoma using the applied antibodies. In contrast, cyclin D1 protein expression was observed in 65% of uveal melanomas; a positive correlation between cyclin D1 cell positivity and tumour cell type, location, growth fraction, as well as with pRB positivity was observed. p53, p21, and p16 could be demonstrated in both tumours. An inverse relation between p53 and p21 expression was demonstrated in most choroidal melanomas and in some retinoblastomas. Apart from a decrease in the growth fractions of the tumours as determined by MIB-1, a significant difference in the expression of G1-S phase transition markers in vital areas of uveal melanoma and retinoblastoma following treatment with radiotherapy and/or chemotherapy was not observed. CONCLUSION: Retinoblastomas and uveal melanomas, two tumours of differing pRB status, differ also in their immunohistochemical pattern for markers of the G1-S phase transition of the cell cycle. The results of the present study support the concept of (a) an autoregulatory loop between pRB and cyclin D1 in tumours with a functional pRB and the disruption of this loop in the presence of pRB mutation, as well as (b) a checkpoint mechanism in late G1, whose regulation via loss of p16 or pRB, or overexpression of cyclin D1 constitutes a common pathway to malignancy. Further, the results raise the possibility of cyclin D1 overexpression having a role in the pathogenesis of uveal melanoma.     

External beam radiation therapy as an agent in the aetiology of carcinoma of the bile duct: a report on two patients

Two cases of biliary duct carcinoma occurring in patients who had received prophylactic abdominal irradiation 17 years previously are described. Although external beam radiation has been implicated in the aetiology of many malignancies, there is only one previous report of it being associated with carcinoma of the bile duct. All patients receiving external beam irradiation for curable malignancies require long term follow-up so that treatment induced malignancies may be detected.     

Limb salvage and outcome of osteosarcoma. The University of Muenster experience

One hundred thirty-six patients with non-metastatic high grade osteosarcoma treated from 1978 to 1994 in one institution with a multidisciplinary approach that included intravenous neoadjuvant chemotherapy were studied to evaluate which factors influence the outcome of modern orthopaedic therapy. Anatomic location, tumor volume, surgical margins, complications, and functional outcome were analyzed. Seventy-nine patients had a limb salvage procedure, 21 had a rotationplasty, and 33 had an amputation. Limb salvage consisted of 32 endoprostheses, 39 allograft replacements, six autograft replacements, and two shortening procedures. Three patients died during preoperative chemotherapy treatment. At a mean followup of 43 months, 81 patients continue to be disease free, three are alive after local recurrence, 17 are alive after having metastatic lesions, five are alive with metastatic lesions present, and 30 patients died of their disease. Forty-seven patients had pulmonary metastatic lesions, 14 had osseous metastatic lesions, three had abdominal metastatic lesions, two had lymphatic metastatic lesions, and eight patients had skip metastatic lesions. Prognosis correlated with chemotherapy response, surgical margins, and tumor volume. The minor complication rate for limb salvage was 4% and the major complication rate was 52%. Amputations had a 6% minor complication rate and 34% major complication rate. Rotationplasties had 10% minor and 48% major complication rates. The Musculoskeletal Tumor Society functional evaluation after limb salvage showed that 23 (38%) patients had more than 75% of the maximum functional score, 34 (56%) were from 50% to 75%, and three (5%) less than 50%. Of the rotationplasties, six (67%) were functionally better than 75% and three (33%) were functionally better than from 50% to 75%. In the group of amputations, 13 (56%) were from 50% to 75%, and 10 (44%) less than 50%. The extent of preoperative necrosis, surgical margins, and tumor volume are the most important prognostic factors. The increase in limb salvage procedures and the better long term survival of patients results in a higher rate of immediate and delayed complications. Functional outcome after rotationplasty is superior to limb salvage reconstruction and amputation.     

Breech extraction of the second twin. 56 cases and review of the literature

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.