Allele-specific CRISPR-Cas9 editing of dominant epidermolysis bullosa simplex in human epidermal stem cells.

Epidermolysis bullosa simplex (EBS) is a rare skin disease inherited mostly in an autosomal dominant manner. Patients display a skin fragility that leads to blisters and erosions caused by minor mechanical trauma. EBS phenotypic and genotypic variants are caused by genetic defects in intracellular proteins whose function is to provide the attachment of basal keratinocytes to the basement membrane zone and most EBS cases display mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes. Besides palliative treatments, there is still no long-lasting effective cure to correct the mutant gene and abolish the dominant negative effect of the pathogenic protein over its wild-type counterpart. Here, we propose a molecular strategy for EBS01 patient's keratinocytes carrying a monoallelic c.475/495del21 mutation in KRT14 exon 1. Through the CRISPR-Cas9 system, we perform a specific cleavage only on the mutant allele and restore a normal cellular phenotype and a correct intermediate filament network, without affecting the epidermal stem cell, referred to as holoclones, which play a crucial role in epidermal regeneration.

[Interposition of the jejunal loop in the surgical treatment of gastroduodenal ulcer, postprandial syndromes and gastric cancer]. / L'interposizione di ansa digiunale nel trattamento chirurgico dell'ulcera gastroduodenale, delle sindromi post-cibali e del cancro gastrico

50 cases of interposition of jejunal loop (32 for gastric cancer and 18 for ulcerous pathology) carried out over the last 3 years are reported. From a technical point of view and as an alternative to degastroenteroanastomosis, interposition of the loop is preferred in partial oral end-to-end on the stomach. In neoplastic lesions, Mouchet-Camey type reconstruction was adopted as a routine measure. After describing the complications of the operation and analyzing the causes, the long-term results are evaluated using absorption curves with 131-I labelled oleic acid. The excellent weight increase in the inflammatory forms, and the lack of reflow and dumping in patients subjected to total gastrectomy for cancer, confirm the value of the technique.

[Cytologic diagnosis of stomach neoplasms]. / Contributo alla diagnosi citologica delle neoplasie gastriche

Personal experience in the cytological diagnosis of gastric neoplasis acquired in a series of 104 patients is presented. Three false positives were detected in 29 cases of supposed malignancy and 11 false negatives in 75 patients with tumours thought to be benign. Cytology often proved the determining factor in the planning of surgery, while in some instances it also gave an indication of the histological type involved.

Tailored excisional treatment for high-grade haemorrhoidal disease.

Patients affected by high-grade haemorrhoid with a fibrous internal pile or an important external component are suitable for an excisional procedure. The aim of this study is to evaluate the outcome of different excisional treatments such as Milligan and Morgan haemorrhoidectomy, Ferguson haemorrhoidectomy and Pexy-excision carried out according to a tailored treatment on each pathological pile. All the consecutive patients that underwent an excisional procedure for high-grade haemorrhoids in two different centres were considered for the present study. From January 2010 to December 2012, 135 patients affected by high-grade haemorrhoidal disease were treated with excisional procedures. No statistically significant differences were noted regarding age, sex distribution, symptoms, Goligher grade, length of surgery, number of pathological piles treated and number of pathological piles excised for each patient between groups. The Ferguson and Pexy-excision procedures yield better results in terms of pain and healing than open haemorrhoidectomy, whereas recurrence and complications are similar after 1 year. Excisional procedures are safe and effective for the treatment of high-grade haemorrhoids mostly if performed according to a tailored project. An increase in the number of pathological piles treated corresponded to an increase in the need of analgesics regardless of the procedure performed.