Ocular and systemic toxicity of high-dose intravitreal topotecan in rabbits: Implications for retinoblastoma treatment.

Although many more eyes of children with retinoblastoma are salvaged now compared to just 10 years ago, the control of vitreous seeding remains a challenge. The introduction of intravitreal injection of melphalan has enabled more eyes to be salvaged safely but with definite retinal toxicity. Intensive treatment with high-dose intravitreal topotecan may be a strategy to control tumor burden because of its cell cycle-dependent cytotoxicity and the proven safety in humans. Therefore, we evaluated the ocular and systemic safety of repeated high-dose intravitreal injections of topotecan in rabbits. Systemic and ocular toxicity was assessed in non-tumor-bearing rabbits after four weekly injections of three doses of topotecan (10 µg, 25 µg, and 50 µg) or vehicle alone. Animals were evaluated weekly for general and ophthalmic clinical status. One week after the last injection, vitreous and plasma samples were collected for drug quantification and the enucleated eyes were subjected to histological assessment. Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. Eyes injected with all topotecan doses or vehicle showed no signs of anterior segment inflammation, clinical or histologic evidence of damage to the retina, and ERG parameters remained unaltered throughout the study. Vitreous and plasma topotecan lactone concentrations were undetectable. Four weekly intravitreal injections of topotecan up to 50 µg in the animal model or a 100 µg human equivalent dose were not toxic for the rabbit eye. High doses of topotecan may show promising translation to the clinic for the management of difficult-to-treat retinoblastoma vitreous seeds.

NEW BNYVV P25 VARIANTS IN BELGIUM.

Rhizomania is a widespread viral plant disease of major importance in sugar beet cropping and breeding. It is caused by the Beet necrotic yellow vein virus (BNYVV), a Benyvirus transmitted by the soil inhabiting plasmodiophorid Polymyxa betae. This vector also transmits other sugar beet virus such as Beet virus Q (BVQ) and Beet soil-borne virus (BSBV). Despite identification of resistance genes, BNYVV remains a major constraint because of resistance-breaking events as well as its ability to survive for long periods in soils in resting spores of P. betae. During the 2014 growing season, severe rhizomania symptoms were detected in Rz1 resistant beet genotypes in ten Belgian fields suggesting resistance-breaking events. Plants from these fields were sampled and total RNA was extracted from root hairs. The presence of BNYVV, BSBV, BVQ and P. betae was assessed by multiplex RT-PCR. Samples were then tested for the presence of BNYVV RNA5 and RNA3 by RT-PCR respectively targeting P26 and P25 genes. PCR products from P25 gene were then purified and sequenced. The results confirmed the presence of P. betae, BSBV and BVQ in all samples. BNYVV was detected in nine fields. Sequencing of P25 partial cDNA sequences revealed the presence of BNYVV types A and B. Two isolates possessed the amino acids motifs AYPR in the so-called tetrad region aa67-70. This motif was previously associated with resistance-breaking events. The Belgian situation will be discussed in the light of the current situation in neighbouring countries.

Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers.

BACKGROUND: This phase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinum-based therapy. PATIENTS AND METHODS: Thirty-seven patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity. The primary end point was the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. Angiogenesis-related proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control. RESULTS: Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with noncontrolled disease, we observed in patients with controlled disease a significant higher baseline level of angiopoietin-1 and a significant early plasma decrease in angiopoietin-1, endoglin, and platelet-derived growth factor-AB. PTEN loss was observed only in patients with PD. CONCLUSIONS: Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.

Metastases of clinically occult testicular seminoma mimicking primary extragonadal retroperitoneal germ cell tumors.

BACKGROUND: Whether extragonadal germ cell tumors develop primarily in the retroperitoneum or whether they are essentially metastases of a primary testicular tumor has long been debated and remains controversial. PATIENTS AND METHODS: Three patients presenting with apparent primary extragonadal retroperitoneal germ cell tumors are reported. Ipsilateral testicular evaluation was extended with palpation, ultrasonography and finally histological examination. RESULTS: The retroperitoneal extragonadal tumors were found during abdominal MSCT. It was a fortuitous finding in the two first patients.The third patient presented with abdominal pain attributed to necrosis of the large mass which was subsequently firstly drained through endoscopic ultrasound-guided transduodenal puncture. The seminomatous nature of the retroperitoneal tumors was obtained through transduodenal echoendoscopic-guided cytopuncture in the first case, celioscopic resection in the second case and delayed percutaneous CT guided biopsy in the third symptomatic case. The first two patients had a history of cryptorchidism with substantial clinical testicular atrophy; ultrasonography showed microlithiasis and a small intratesticular tumor in the first patient and an hypoechoic but rather homogeneous atrophic testis in the other; orchiectomy confirmed small seminomatous intratesticular tumors in the two cases. The third patient had an atypical hypoechoic area on testicular ultrasound and histopatholgy revealed a burn-out primary tumor. CONCLUSIONS: So-called primary extragonadal retroperitoneal germ cell tumors are extremely rare and should first be considered as metastases of a viable or burned-out testicular cancer until proven otherwise. All ipsilateral testicular abnormalities revealed by the patient's history, clinical examination and mostly by testicular ultrasound must be treated adequately with orchiectomy because they may act as a sanctuary for later tumor growth.

A Belgian registry of interleukin-2 administration for treatment of metastatic renal cell cancer and confrontation with literature data.

In an effort to map the use of interleukin-2 (IL-2) treatment in patients with clear cell renal cell cancer (RCC) in Belgian hospitals, 44 cases were registered from 9 hospitals between February 2003 and June 2006. It was demonstrated that the majority of these patients were treated with subcutaneous (SC) IL-2. Other methods such as the inhalation of the drug in case of intrathoracic disease or high dose intravenous (IV) administration were much less frequent (3 and 0 cases in this registry, respectively). The results of antitumour activity (around 16% partial response-absence of complete responses) and toxicity of this drug correlate with observations from the literature with the SC administration. In view of the poor results and tolerance with the currently used cytokines (IL-2 or interferon-alfa), much hope is directed towards the development of the novel targeted drugs like sunitinib or sorafenib used alone or in combination with cytokines in this disease.

Carcinoid tumor of the small intestine: MDCT findings with pathologic correlation.

BACKGROUND: MDCT currently frequently represents the first choice modality for imaging in acute or subacute abdominal conditions implicating the small bowel. As a consequence, the MDCT features of intestinal carcinoid tumors and of their peculiar metastatic spread have to be known by abdominal radiologists. PATIENTS AND METHODS: These features are described and illustrated in the retrospective review of seven proven cases of small intestine carcinoids diagnosed and treated in our institution. The findings are described and correlated with gross anatomy specimens. RESULTS: The primary tumour clearly appeared as a contrast-enhancing intraluminal lesion in all cases except in one case in which the primary lesion remained unlocalized and in another in which the primary tumour finally appeared infracted at gross anatomy. The maximal tumoral enhancement was obtained in 3 patients imaged during the acute arterial phase. The diameter of the primary tumour ranged from 1 to 3 cm and all masses were ileal comprising one lesion in the proximal ileum, two in the medium ileum and three in the distal ileum. 6/7 patients had multiple prominent mesenteric nodal metastases, all also appearing as hypervascularised enhancing masses. In 4/7 patients the nodal metastases represented the major finding being much prominent and larger than the primary tumour. Signs of retractile mesenteritis with soft tissue stranding, retraction and stellate pattern of the mesentery were found around the mesenteric metastases in 5/7 patients and direct incarceration of vessels were found in 3 cases. CONCLUSION: The analysis of the arterial phase of MDCT study appears primordial to detect the sometimes very small but intensively enhancing primary tumor and to delineate encasement or direct obstruction of mesenteric vessels frequently caused by enhancing nodal metastases which volume often exceeds that of the primary tumor. Secondary retractile mesenteritis, deformation or ischemia of bowel loops, and hypervascular hepatic metastases are typical associated findings.

A retrospective study of laser in situ keratomileusis after radial keratotomy.

PURPOSE: This is a retrospective study designed to present results of laser in situ keratomileusis (LASIK) after radial keratotomy (RK). METHODS: Eighty eyes of 56 patients underwent LASIK for residual myopia, astigmatism, and hyperopia after RK. Absolute mean preoperative spherical equivalent refraction was 2.36 +/- 1.17 D. Best spectacle-corrected visual acuity (BSCVA) was 20/20 in 56% of eyes, 20/25 in 25%, 20/30 in 13%, 20/40 in 5%, and 20/60 in 1%. Uncorrected visual acuity was better than 20/40 in four eyes. Follow-up ranged from a minimum of 1 day after surgery to a maximum of 2 years, with an average of 6 months. RESULTS: Mean final absolute spherical equivalent refraction was 0.62 +/- 0.611 D. Six eyes experienced a loss of BSCVA of one line, one eye lost two lines, and one lost more than two lines. Three eyes had one line of improvement and one eye had two lines of improvement. Uncorrected visual acuity was 20/20 in 21 eyes, 20/25 in 20 eyes, and 20/30 in 19 eyes. There was stromal opacity in two eyes, epithelial defects in two eyes, and epithelial ingrowth in four eyes. CONCLUSION: LASIK may be an effective treatment for myopia, astigmatism, and hyperopia in patients with residual refractive error after RK. Extreme caution should be exercised due to the complexity of this group of patients.

Reactivity of hair cystine in microemulsion media.

Synopsis Reduction of keratin cystine by thioglycolic acid incorporated in microemulsions of the water/sodium dodecilsulphate/n-pentanol/n-dodecane system has been determined. The results obtained have been interpreted in relation to the properties of the reaction media. Microemulsions with constant oil-to-surface active mixture weight ratios (R(o/s)) and different concentrations of water were chosen as reaction media. At low water concentrations a steep increase in reactivity with the increase of water was observed at all values of R(o/s). However it was more pronounced the higher the oil content. A relation between maximum cysteine formation and percolative behaviour of the microemulsion was found at high R(o/s) values.

Influence of microemulsion structure on cystine reactivity with keratin fibres.

Summary The activity of thioglycolic acid, incorporated in a microemulsion, towards cystine residues present in keratin proteins has been investigated. In an attempt to relate the structural state of the microemulsions to cystine reactivity, an appropriate model system showing a large microemulsion domain with diverse structures was chosen. The realm of preferentially hydrocarbon-continuous microemulsion-type media was found to induce the highest activity.