To report the efficacy of super-selective intra-ophthalmic artery melphalan (IAM) for the treatment of refractory retinoblastoma and any associated complications of this treatment.
A prospective case ...series.
Eyes with retinoblastoma that had been treated with systemic chemotherapy or local therapy and had a relapse of their condition.
All patients receiving IAM between May 2009 and September 2010 were included in the study. Intra-ophthalmic artery melphalan was offered to patients who had failed to respond adequately to systemic chemotherapy and local treatment where appropriate or because of a new recurrence of retinoblastoma that could not be treated with local therapies. None of the patients were excluded because of central nervous system abnormalities. Patients received 2 treatments of IAM given 4 weeks apart. All patients received an orthoptic assessment 3 weeks after each treatment and an examination under anesthesia (EUA). A third treatment was given if an unsatisfactory response was observed on EUA after 2 treatments.
The response of the retinoblastoma tumor(s) and any associated local side effects from the treatment.
A total of 15 eyes in 14 patients were treated with IAM during the study period. The mean age at the time of IAM was 31.5 months (median 17.3, range 11.2-150.7 months), and the mean follow-up was 8.7 months (3-16.3 months). Tumor control was achieved in 12 eyes (80%), and 12 eyes (80%) had local side effects that included third cranial nerve palsy in 6 (40%), orbital edema in 3 (20%), permanent retinal detachment in 1 (7%), and vitreous hemorrhage in 4 (27%). Seven eyes (47%) developed significant retinal pigment epithelium changes.
Intra-ophthalmic artery melphalan is an effective treatment for retinoblastoma, achieving a high level of remission in refractory tumors. It can be associated with significant local side effects that can result in loss of vision and possible amblyogenesis. Clinicians and parents need to consider the benefits and potential local side effects before embarking on treatment.
Hypocalcaemia causes neuromuscular and myocardial symptoms, including QT interval prolongation, and cardiac arrhythmias. Prompt detection and calcium replacement may reverse the pathology, following ...which the underlying cause should be diagnosed and treated to prevent recurrence. I present the case of a young man presenting with collapse who was found to have sinus rhythm with significant QT interval prolongation on admission electrocardiogram (ECG) associated with profound hypocalcaemia secondary to primary hypoparathyroidism.
To evaluate the rate and identify the risk factors for high-risk histopathologic features in group D retinoblastoma eyes enucleated as primary or secondary treatment.
Retrospective analysis.
A total ...of 64 enucleated group D eyes (62 patients), of which 40 (40 patients) were primary and 24 (22 patients) were secondary to other treatments.
Clinicopathologic correlation of consecutive group D eyes enucleated from 2002 to 2014. High-risk histopathologic features were defined as the presence of anterior chamber seeds, iris infiltration, ciliary body/muscle infiltration, massive (≥3 mm) choroidal invasion, retrolaminar optic nerve invasion, or combined non-massive choroidal and prelaminar/laminar optic nerve invasion.
High-risk histopathologic features, metastasis, and death.
Of the 64 group D eyes, 37 (58%) were classified as cT2bN0M0H0, 24 (38%) were classified as cT2bN0M0H1, and 3 (5%) were classified as cT2aN0M0H1, according to the 8th edition cTNMH Retinoblastoma Staging. High-risk histopathologic features were detected in 10 eyes (16%) in the entire cohort, 5 eyes (13%) of the primary enucleated group (pT3aNxM0, n = 2 and pT3bNxM0, n = 3, 8th edition pTNM), and 5 eyes (21%) of the secondary enucleated group (pT2bNxM0, n = 2, pT3aNxM0, n = 2 and pT3cNxM0, n = 1). Absence of vitreous seeds at presentation was the only predictive factor found for high-risk histopathologic features in the primary enucleation group (P = 0.042), whereas none were found in the secondary group (P ≥ 0.179). Invasion of the anterior structures (anterior chamber, iris, ciliary body/muscle) was detected significantly more after secondary enucleation (P = 0.048). All patients with high-risk histopathologic features were treated with adjuvant chemotherapy, and no metastases were recorded in a median follow-up time of 73.2 months (mean, 71.5; range, 13.7-153.0).
The choice of primary treatment for group D retinoblastoma should be carefully weighed, because according to this study, 13% of eyes harbor high-risk histopathologic features at presentation, with the absence of vitreous seeds being a potential risk factor. It is of special importance in group D eyes being considered for nonsystemic treatment, such as primary intraophthalmic artery chemotherapy. Secondary enucleated group D eyes with high-risk histopathologic features more commonly involved anterior structures, warranting meticulous clinical and histologic examinations for this subset of patients.
Retinoblastoma (RB) is the most common intraocular pediatric cancer. Nearly all cases of RB are associated with mutations compromising the function of the RB1 tumor suppressor gene. We previously ...demonstrated that PRELP is widely downregulated in various cancers and our in vivo and in vitro analysis revealed PRELP as a novel tumor suppressor and regulator of EMT. In addition, PRELP is located at chromosome 1q31.1, around a region hypothesized to be associated with the initiation of malignancy in RB. Therefore, in this study, we investigated the role of PRELP in RB through in vitro analysis and next-generation sequencing. Immunostaining revealed that PRELP is expressed in Müller glial cells in the retina. mRNA expression profiling of PRELP−/− mouse retina and PRELP-treated RB cells found that PRELP contributes to RB progression via regulation of the cancer microenvironment, in which loss of PRELP reduces cell–cell adhesion and facilitates EMT. Our observations suggest that PRELP may have potential as a new strategy for RB treatment.
The identification of somatic
variation is crucial to confirm the heritability of retinoblastoma. We and others have previously shown that, when tumour DNA is unavailable, cell-free DNA (cfDNA) ...derived from aqueous humour (AH) can be used to identify somatic
pathogenic variation. Here we report
pathogenic variant detection, as well as cfDNA concentration in an extended cohort of 75 AH samples from 68 patients. We show cfDNA concentration is highly variable and significantly correlated with the collection point of the AH. Cell-free DNA concentrations above 5 pg/µL enabled the detection of 93% of known or expected
pathogenic variants. In AH samples collected during intravitreal chemotherapy treatment (Tx), the yield of cfDNA above 5 pg/µL and subsequent variant detection was low (≤46%). However, AH collected by an anterior chamber tap after one to three cycles of primary chemotherapy (Dx1+) enabled the detection of 75% of expected pathogenic variants. Further limiting our analysis to Dx1+ samples taken after ≤2 cycles (Dx ≤ 2) provided measurable levels of cfDNA in all cases, and a subsequent variant detection rate of 95%. Early AH sampling is therefore likely to be important in maximising cfDNA concentration and the subsequent detection of somatic
pathogenic variants in retinoblastoma patients undergoing conservative treatment.
Abstract Purpose To analyse the long-term visual acuity, strabismus and nystagmus outcomes in Group D retinoblastoma following multimodality treatments in a national retinoblastoma referral centre. ...Design Retrospective interventional case series. Methods A 13-year retrospective chart review of Group D eyes treated initially with intravenous chemotherapy (IVC) and followed-up for at least 1 year from last treatment. Risk factors for final visual acuity (VA) were analysed, and rate of strabismus and nystagmus at last follow-up visit were calculated. Results One hundred and four Group D eyes (92 patients) presented to our centre during the study period, of which 32 (27 patients) met the inclusion criteria. Following IVC (vincristine, etoposide and carboplatin), adjuvant treatments included intra-ophthalmic artery chemotherapy in 5 (16%) eyes, plaque brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%) and cryotherapy in 24 (75%) eyes. On last examination, 64.41 ± 6.76 months from presentation, mean final VA was 20/283 (logMAR equivalent of 1.15±0.15). On univariate analysis, presentation age, foveal retinoblastoma (at initial examination), use of TTT and tumour-foveola distance (at last visit) were found to be significant risk factors for worse VA (p<0.026). On multivariate analysis, however, only TTT was found to be significant (p=0.010). At last visit, 6/27 (22%) patients had nystagmus and 12/20 (60%) of bilaterally salvaged patients had strabismus (n=10 exotropia and n=2 esotropia). Conclusions Following multimodality treatments initiated with IVC, 50% of salvaged Group D retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse vision, 60% had strabismus and 22% nystagmus.
Adjuvant use of laser with systemic chemotherapy for treatment of retinoblastoma may reduce recurrence rates while also causing local side effects. Information is lacking on the effect of laser on ...visual outcomes.
A retrospective review of two retinoblastoma centres in the United Kingdom was conducted. Patients were included if there was a macular tumour in at least one eye. Eyes that received chemotherapy alone were compared with eyes that received chemotherapy plus adjuvant laser.
A total of 76 patients and 91 eyes were included in the study. Systemic chemotherapy alone was used in 71 eyes while chemotherapy plus laser was used in 20 eyes. Demographic characteristics of both groups were similar. Macular relapse rates were similar between groups: 22/71 (31%) eyes in chemotherapy group and 9/20 (45%) eyes in laser group (p=0.29). There was no increase in vitreous relapses in the laser group (2/20 eyes), compared with the chemotherapy group 10/71 eyes (p=0.99). Survival analysis demonstrated similar time to first relapse between groups. Final visual acuity was equal between groups with 6/15 or better present in 31.1% of eyes in the chemotherapy group and 37.5% of eyes in the laser group (p=0.76). Presence of tumour at the fovea was predictive of final visual acuity, regardless of treatment group.
Adjuvant laser in the treatment of retinoblastoma is safe and does not lead to increased rate of vitreous recurrence. Final visual acuity is determined by the presence of tumour at the fovea and not the use of laser.
Introduction
Atrial fibrillation (AF) is frequent after any cardiac surgery, but evidence suggests it may have no significant impact on survival if sinus rhythm (SR) is effectively restored early ...after the onset of the arrhythmia. In contrast, management of preoperative AF is often overlooked during or after cardiac surgery despite several proposed protocols. This study sought to evaluate the impact of preoperative AF on mortality in patients undergoing isolated surgical aortic valve replacement (AVR).
Methods
We performed a retrospective, single‐center study involving 2628 consecutive patients undergoing elective, primary isolated surgical AVR from 2008 to 2018. A total of 268/2628 patients (10.1%) exhibited AF before surgery. The effect of preoperative AF on mortality was evaluated with univariate and multivariate analyses.
Results
Short‐term mortality was 0.8% and was not different between preoperative AF and SR cohorts. Preoperative AF was highly predictive of long‐term mortality (median follow‐up of 4 years Q1–Q3 2–7; hazard ratio HR: 2.24, 95% confidence interval CI: 1.79–2.79, p < .001), and remained strongly and independently predictive after adjustment for other risk factors (HR: 1.54, 95% CI: 1.21–1.96, p < .001) compared with preoperative SR. In propensity score‐matched analysis, the adjusted mortality risk was higher in the AF cohort (OR: 1.47, 95% CI: 1.04–1.99, p = .03) compared with the SR cohort.
Conclusions
Preoperative AF was independently predictive of long‐term mortality in patients undergoing isolated surgical AVR. It remains to be seen whether concomitant surgery or other preoperative measures to correct AF may impact long‐term survival.
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