Esophageal Small Cell Carcinoma with Synchronous Renal Cell Carcinoma: A Case Report with Review of the Literature

Synchronous malignancies with an esophageal malignancy are not uncommon. However synchronous esophageal and renal cell carcinoma (RCC) is rare with only 11 cases reported in the world literature, the esophageal malignancies being adenocarcinomas or squamous cell carcinomas. Here, we report the first case of synchronous small cell carcinoma (SCC) of the esophagus with a RCC. SCC of the esophagus is an aggressive malignancy with poor prognosis constituting 0.8–2.4% of all esophageal malignancies, currently treated with induction chemotherapy followed by chemoradiotherapy. Our patient underwent chemoradiotherapy for the SCC of the esophagus followed by radical nephrectomy for the RCC. He developed metastatic disease and died 8 months after diagnosis. Larger case series are required to develop a treatment algorithm for such a rare presentation. The key points of this report are: (1) Synchronous RCC with a primary esophageal carcinoma is a rare presentation. (2) This is the first described case report of a SCC of the esophagus with a synchronous RCC. (3) Overall prognosis in a synchronous presentation is determined by the primary esophageal malignancy. (4) Esophageal carcinomas with synchronous malignancies have a poorer prognosis compared to isolated esophageal carcinoma

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE

Muscle MRI at the time of questionable disease flares in Juvenile Dermatomyositis (JDM)

Abstract Background The course of JDM has improved substantially over the last 70 years with early and aggressive treatments. Yet it remains difficult to detect disease flares as symptoms may be mild; signs of rash and muscle weakness vary widely and are often equivocal; laboratory tests of muscle enzyme levels are often normal; electromyography and muscle biopsy are invasive. Alternative tools are needed to help decide if more aggressive treatment is needed. Our objective is to determine the effectiveness of muscle Magnetic Resonance Imaging (MRI) in detecting JDM flares, and how an MRI affects physician’s decision-making regarding treatment. Methods This study was approved by the Institutional Review Board of Nationwide Children’s Hospital. JDM patients were consulted between 1/2005 and 6/2015. MRIs were performed on both lower extremities without contrast sequentially: axial T1, axial T2 fat saturation, axial and coronal inversion recovery, and axial diffusion weighted. The physician decision that a JDM patient was in a flare was considered the gold standard. MRI results were compared with physician’s decisions on whether a relapse had occurred, and if there was a concordance between the assessment methods. Results Forty-five JDM patients were studied. Eighty percent had weakness at diagnosis, 100% typical rash, and 73% typical nail-fold capillary changes. At diagnosis, muscle enzymes were compatible with JDM generally (CK 52%, LDH 62%, aldolase 72%, AST 54% abnormal). EMG was abnormal in 3/8, muscle biopsy typical of JDM in 10/11, and MRI abnormal demonstrating myositis in 31/40. Thirteen patients had a repeat MRI for possible flares with differing indications. Three repeat MRI’s were abnormal, demonstrating myositis. There was moderate agreement about flares between MRI findings and physician’s treatment decisions (kappa = 0.59). In each abnormal MRI case the physician decided to increase treatment (100% probability for flares). MRI was negative for myositis in 10 patients, by which 7/10 the physicians chose to continue or to taper the medications (70% probability for non-flares). Conclusion A muscle MRI would facilitate objective assessments of JDM flares. When an MRI shows myositis, physicians tend to treat 100% of the time. When an MRI shows no myositis, physicians continued the same medications or tapered medications 70% of the time. Further studies would help confirm the utility and cost-effectiveness of MRI to determine JDM flares

Genomic pathology of SLE-associated copy-number variation at the FCGR2C/FCGR3B/FCGR2B locus

Reduced FCGR3B copy number is associated with increased risk of systemic lupus erythematosus (SLE). The five FCGR2/FCGR3 genes are arranged across two highly paralogous genomic segments on chromosome 1q23. Previous studies have suggested mechanisms for structural rearrangements at the FCGR2/FCGR3 locus and have proposed mechanisms whereby altered FCGR3B copy number predisposes to autoimmunity, but the high degree of sequence similarity between paralogous segments has prevented precise definition of the molecular events and their functional consequences. To pursue the genomic pathology associated with FCGR3B copy-number variation, we integrated sequencing data from fosmid and bacterial artificial chromosome clones and sequence-captured DNA from FCGR3B-deleted genomes to establish a detailed map of allelic and paralogous sequence variation across the FCGR2/FCGR3 locus. This analysis identified two highly paralogous 24.5 kb blocks within the FCGR2C/FCGR3B/FCGR2B locus that are devoid of nonpolymorphic paralogous sequence variations and that define the limits of the genomic regions in which nonallelic homologous recombination leads to FCGR2C/FCGR3B copy-number variation. Further, the data showed evidence of swapping of haplotype blocks between these highly paralogous blocks that most likely arose from sequential ancestral recombination events across the region. Functionally, we found by flow cytometry, immunoblotting and cDNA sequencing that individuals with FCGR3B-deleted alleles show ectopic presence of FcγRIIb on natural killer (NK) cells. We conclude that FCGR3B deletion juxtaposes the 5′-regulatory sequences of FCGR2C with the coding sequence of FCGR2B, creating a chimeric gene that results in an ectopic accumulation of FcγRIIb on NK cells and provides an explanation for SLE risk associated with reduced FCGR3B gene copy number

Subjective Well-Being, Societal Condition and Social Policy – The Case Study of a Rich Chinese Society

attitude study, life satisfaction, social policy, subjective well-being, welfare indicators,