Conjunctival Melanoma in Asian Indians: A Study of 42 Patients

Purpose: To describe the clinical features, treatment, and outcomes of conjunctival melanoma in Asian Indians.

Methods: Retrospective study of 42 patients.

Results: The mean age at presentation of conjunctival melanoma was 43 years (median, 45 years; range, 9–78 years). There were 20 (48%) males and 22 (52%) females. Nineteen patients (45%) had a known history of a preexisting pigmented conjunctival lesion. Bulbar conjunctiva (n = 28; 67%) was the most common tumor epicenter, and medial ocular surface quadrant (n = 15; 36%) was more commonly involved. The mean tumor basal diameter was 12 mm (median, 10 mm; range, 4–30 mm), and the mean tumor thickness was 4 mm (median, 2 mm; range, 1–30 mm). Majority of the patients had a pigmented tumor (n = 33; 79%). The tumors arose de novo (n = 17, 41%) or were associated with conjunctival nevus (n = 9; 21%) or primary acquired melanosis (n = 16, 38%). Wide excisional biopsy, adjunctive cryotherapy, and amniotic membrane grafting were performed in 27 (71%) patients, 11 (29%) underwent orbital exenteration, and 4 were lost to follow-up prior to definitive treatment. Over a mean follow-up period of 24 months (median, 9 months; range, <1 to 136 months), four (11%) patients had tumor recurrence, seven (18%) had locoregional lymph node metastasis, and four (11%) developed systemic metastasis and died due to metastatic disease.

Conclusion: Conjunctival melanoma predominantly occurs in middle-aged Asian Indians and is associated with a high rate of systemic metastasis and death.     

Retinoblastoma: Achieving new standards with methods of chemotherapy

The management of retinoblastoma (RB) has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC) is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC) is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms “RB,” and “treatment,” “chemotherapy,” “systemic chemotherapy,” “IVC,” “IAC,” “periocular chemotherapy,” or “intravitreal chemotherapy.” Relevant English language articles were extracted, reviewed, and referenced appropriately.     

Dissections of regional lymph nodes for treatment of skin cancer: predicting annual caseloads that will optimise outcomes

IntroductionDissection of regional lymph nodes (RLNs) can lead to significant morbidity and a high prevalence of complications. Published guidance states that these procedures should be carried out by surgeons who are members of a specialist skin multidisciplinary team who carry out a combined minimum of 15 axillary/groin dissections per year. However, there is little evidence to guide this minimum figure of procedures. We report on the burden of service provision and prevalence of complications across the South West of England and Wales.MethodsA 12-month review of dissections of RLNs for skin cancer was undertaken covering five Plastic Surgery Units with a collective catchment of 8.4 million people. Detailed data were collected on patient demographics, pathology, timing of surgery, and prevalence of complications.ResultsA total of 163 dissections were carried out. Forty-three per cent of patients experienced one or more complication. In that 12-month period, an average of 8 axillary/groin dissections was carried out per surgeon. A funnel plot demonstrated that the prevalence of complications for individual surgeons was within the limit of the plot but, in many cases, this was based only on a relatively small number of procedures per consultant. If surgeons carried out 10 procedures per year, the upper and lower limits on the plot were 73% and 11%, respectively.ConclusionsFunnel plots can provide a useful guide as to whether the prevalence of complications for procedures for individual surgeons lies within acceptable limits. Based on these results, 10 procedures per consultant per year should be sufficient to enable meaningful assessment of the prevalence of complications.     

Aurora Kinase B Expression,Its Regulation and Therapeutic Targeting in Human Retinoblastoma

PurposeAurora kinase B (AURKB) plays a pivotal role in the regulation of mitosis and is gaining prominence as a therapeutic target in cancers; however, the role of AURKB in retinoblastoma (RB) has not been studied. The purpose of this study was to determine if AURKB plays a role in RB, how its expression is regulated, and whether it could be specifically targeted.MethodsThe protein expression of AURKB was determined using immunohistochemistry in human RB patient specimens and immunoblotting in cell lines. Pharmacological inhibition and shRNA-mediated knockdown were used to understand the role of AURKB in cell viability, apoptosis, and cell cycle distribution. Cell viability in response to AURKB inhibition was also assessed in enucleated RB specimens. Immunoblotting was employed to determine the protein levels of phospho-histone H3, p53, p21, and MYCN. Chromatin immunoprecipitation–qPCR was performed to verify the binding of MYCN on the promoter region of AURKB.ResultsThe expression of AURKB was found to be markedly elevated in human RB tissues, and the overexpression significantly correlated with optic nerve and anterior chamber invasion. Targeting AURKB with small-molecule inhibitors and shRNAs resulted in reduced cell survival and increased apoptosis and cell cycle arrest at the G2/M phase. More importantly, primary RB specimens showed decreased cell viability in response to pharmacological AURKB inhibition. Additional studies have demonstrated that the MYCN oncogene regulates the expression of AURKB in RB.ConclusionsAURKB is overexpressed in RB, and targeting it could serve as a novel therapeutic strategy to restrict tumor cell growth.     

Crosslinguistic semantic and translation priming in normal bilingual individuals and bilingual aphasia

The present study examined lexical representation in early Spanish‐English bilinguals using an unmasked semantic and translation priming paradigm. In Experiment 1, participants were divided into two groups based on performance (more‐balanced bilinguals, MB and less‐balanced bilinguals, LB) on the experimental task. In Experiment 2, four patients with bilingual aphasia (BA) performed the same experiment. Results from both experiments revealed that all groups were more accurate for English targets (S‐E direction) than Spanish targets (S‐E direction). In Experiment 1, semantic priming was observed from English to Spanish in both the LB and MB groups although the effect was greater for the LB group. Further, only the LB group showed priming from Spanish to English. For both normal groups, there was no difference between translation and semantic priming effects. In Experiment 2, patients with bilingual aphasia demonstrated different patterns of activation with no clear trends. Two participants demonstrated greater priming from Spanish to English whereas two participants demonstrated the opposite effect.     

How justice can affect jury: Training abstract words promotes generalisation to concrete words in patients with aphasia

Developing language treatments that not only improve trained items but also promote generalisation to untrained items is a major focus in aphasia research. This study is a replication and extension of previous work which found that training abstract words in a particular context-category promotes generalisation to concrete words but not vice versa (Kiran, Sandberg, & Abbott, 2009 Kiran, S., Sandberg, C., & Abbott, K. (2009). Treatment for lexical retrieval using abstract and concrete words in persons with aphasia: Effect of complexity. Aphasiology, 23, 835–853. doi: 10.1080/02687030802588866[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Twelve persons with aphasia (five female) with varying types and degrees of severity participated in a generative naming treatment based on the Complexity Account of Treatment Efficacy (CATE; Thompson, Shapiro, Kiran, & Sobecks, 2003 Thompson, C., Shapiro, L., Kiran, S., & Sobecks, J. (2003). The role of syntactic complexity in treatment of sentence deficits in agrammatic aphasia: The Complexity Account of Treatment Efficacy (CATE). Journal of Speech, Language, and Hearing Research, 46, 591–607. doi: 10.1044/1092-4388(2003/047)[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). All participants were trained to generate abstract words in a particular context-category by analysing the semantic features of the target words. Two other context-categories were used as controls. Ten of the twelve participants improved on the trained abstract words in the trained context-category. Eight of the ten participants who responded to treatment also generalised to concrete words in the same context-category. These results suggest that this treatment is both efficacious and efficient. We discuss possible mechanisms of training and generalisation effects.     

Clinical presentation and outcome of retinoblastoma based on age at presentation: a review of 1450 children

To compare the clinical presentation and outcomes of retinoblastoma (RB) based on age at presentation. Retrospective comparative study of 1940 eyes of 1450 children with RB. Presentation of RB with enlarged eyeball and eyelid swelling (2% and < 1% in ≤ 1 year, 4% and 2% in > 1–2 years, 7% and 2% in > 2–3 years, and 12% and 4% in > 3 years; p < 0.0001 and p = 0.05, respectively) is more common with increasing age. Based on the 8th edition of American Joint Committee Classification, T1 is more common in children younger than 1 year (27%), while T4 is more common in children > 3 years of age (20%) (p < 0.0001). Kaplan–Meier (KM) estimate at 1 and 5 years for globe salvage was 64% and 58% in children ≤ 1 year of age versus 30% and 20% in children > 3 years, respectively [Hazard ratio (HR) = 2.48; p < 0.0001], and KM estimate at 1 and 5 years for life salvage was 99% and 97% in children ≤ 1 year of age versus 89% and 78% in children older than 3 years, respectively (HR = 7.65; p < 0.0001). Uncommon clinical features of RB including enlarged eyeball and eyelid swelling are more common with increasing age. Younger age at presentation with RB is associated with better prognosis including higher chances of life and globe salvage.     

Plasma Apolipoprotein L1 Levels Do Not Correlate with CKD

Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m² (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.Nondiabetic CKD in individuals of African ancestry have been linked to polymorphisms in the gene for apolipoprotein L1 (APOL1),^1–5 a protein component of HDL particles with a known function in the immune clearance of Trypanosoma brucei infections.⁶ CKD is associated with two coding variants of the APOL1 gene known as G1 and G2, both of higher allele frequency in African and African descendent populations compared with white populations where they are almost absent. Evidence suggests that the prevalence of the G1 and G2 variants may have increased in African populations because of a selective advantage from their ability to kill a broader range of Trypanosoma species.^1,2,7 Individuals carrying at least one G1 or G2 allele have additional protection from trypanosomiasis; however, individuals with two G1 or G2 alleles are at increased risk for nondiabetic CKD.^2,4,5The pathogenic mechanisms responsible for CKD associated with APOL1 risk variants are unknown. We recently showed that, in addition to being secreted and circulated in the blood,⁸ APOL1 is localized in podocytes, proximal tubular epithelial cells, and small-artery endothelium in normal kidney.⁹ Thus, the contribution of circulating versus kidney-localized variant APOL1s to CKD pathogenesis is unknown. In kidney transplantation, two studies suggest that graft loss is associated with the APOL1 genotype of the allograft, not the recipient.^10,11 However, the association of APOL1 plasma levels with CKD phenotypes or APOL1 genotype has not been studied.To address these issues, we examined circulating APOL1 levels with APOL1 genotype and renal function in HIV-infected African Americans in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort because the occurrence of HIV-associated nephropathy (HIVAN) and renal outcomes in HIV-infected patients are strongly associated with APOL1 risk alleles.^12–14 In addition, we examined the relationship between circulating APOL1 levels and proinflammatory cytokines known to induce APOL1 expression and previously associated with CKD and HIV/AIDS progression.^15,16 Additional analyses examined associations of APOL1 levels with dyslipidemia and the role of APOL1 genotype on CKD progression using longitudinal data.