Closure of a nonhealing gastrocutaneous fistula using argon plasma coagulation and endoscopic hemoclips

A case in which a gastrocutaneous fistula developed after percutaneous endoscopic gastrostomy tube placement is presented. The fistula was first managed conservatively, then was closed by argon plasma coagulation and hemoclip placement. The patient was observed and was discharged once the gastrocutaneous fistula closed.     

Consistent copy number changes and recurrent PRKAR1A mutations distinguish Melanotic Schwannomas from Melanomas: SNP‐array and next generation sequencing analysis

Melanotic Schwannomas (MS) are rare tumors that share histological features with melanocytic tumors and schwannomas. However, their genetics are poorly understood. To elucidate the genetic characteristics of MS, we performed genome‐wide studies in a series of cases. Twelve MS cases were available for the study. Genomic DNAs extracted from formalin‐fixed paraffin embedded tumor tissues were subjected to copy number (CN) and allelic imbalance (AI) analysis by Single Nucleotide Polymorphism (SNP)‐array and screened for mutations in coding exons of 341 key cancer‐associated genes using a hybrid capture‐based next‐generation sequencing (NGS) assay. Sanger sequencing was used to further verify recurrent mutations detected by NGS study. SNP‐array analysis revealed remarkably stereotypic chromosomal abnormalities in MS. Hypodiploidy was common, typically involving monosomies of chromosomes 1, 2, and 17. All 12 samples showed mutations in PRKAR1A gene, including 2 cases with 2 mutations each. The 14 mutations were scattered across PRKAR1A, and most were inactivating mutations. AI on 17q, presenting as loss of heterozygosity with or without CN losses, combined with a PRKAR1A mutation was observed in 9/12 MS cases. The remaining 3 cases included the two samples harboring two mutations in PRKAR1A. MS exhibits a stereotypic pattern of chromosomal losses. In contrast, melanomas are typically characterized by the presence of multiple CN aberrations, without demonstrable differences in the frequency of losses and gains. Inactivation of both alleles of PRKAR1A by “two hits” observed in almost all cases underscores the central role of PRKAR1A in the pathogenesis of this neoplasm. © 2015 Wiley Periodicals, Inc.     

Continuation rates and reasons for discontinuation of intra-uterine device in three provinces of Pakistan: results of a 24-month prospective client follow-up

Background

Long-acting reversible contraceptives, such as the intrauterine device (IUD), remain underutilised in Pakistan with high discontinuation rates. Based on a 24-month prospective client follow-up (nested within a larger quasi-experimental study), this paper presents the comparison of two intervention models, one using private mid-level providers branded as “Suraj” and the other using community midwives (CMWs) of Maternal Newborn and Child Health Programme, for method continuation among IUD users. Moreover, determinants of IUD continuation and the reasons for discontinuation, and switching behaviour were studied within each arm.

Methods

A total of 1,163 IUD users, 824 from Suraj and 339 from the CMW model, were enrolled in this 24-month prospective client follow-up. Participants were followed-up by female community mobilisers physically every second month to ascertain continued IUD usage and to collect information on associated factors, switching behaviour, reasons for discontinuation, and pregnancy occurrence. The probabilities of IUD continuation and the risk factors for discontinuation were estimated by life table analysis and Cox proportional-hazard techniques, respectively.

Results

The cumulative probabilities of IUD continuation at 24 months in Suraj and CMW models were 82% and 80%, respectively. The difference between the two intervention areas was not significant. The probability distributions of IUD continuation were also similar in both interventions (Log rank test: χ² = 0.06, df = 1, P = 0.81; Breslow test: χ² = 0.6, df = 1, P = 0.44). Health concerns (Suraj = 57.1%, CMW = 38.7%) and pregnancy desire (Suraj = 29.3%, CMW = 40.3%) were reported as the most prominent reasons for IUD discontinuation in both intervention arms. IUD discontinuation was significantly associated with place of residence in Suraj and with age (15–25 years) in the CMW model.

Conclusion

CMWs and private providers are equally capable of providing quality IUD services and ensuring higher method continuation. Pakistan’s National Maternal Newborn and Child Health programme should consider training CMWs and providing IUDs through them. Moreover, private sector mid-level providers could be engaged in promoting the use of IUDs.

     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.