A tailored rhomboid mucocutaneous advancement flap to treat anal stenosis.

AIM: Anal stenosis (AS) is a rare but disabling disorder that often represents a complication of anorectal surgery. The aim of our study was to assess the safety and functional outcome of a modified rhomboid flap (MRF) in the treatment of moderate and severe AS. METHODS: Between January 2002 and September 2017, 50 consecutive patients with moderate and severe AS who underwent an MRF were retrospectively included. Anal continence (Cleveland Clinic Incontinence Score) and symptoms (Obstructed Defaecation Syndrome Score) were assessed preoperatively and postoperatively at 12 months. Furthermore, anal calibre was measured both preoperatively and postoperatively at 1, 6 and 12 months. RESULTS: The mean follow-up period was 97 ± 48.3 (33-180) months. The main aetiology was a previous excisional haemorrhoidectomy (N = 23; 46%). The mean preoperative anal calibre was 9.96 ± 2.68 (5-15) mm and there was a statistically significant improvement in all three periods (P < 0.0001) of postoperative evaluation (1, 6 and 12 months) with a mean difference, obtained comparing preoperative and 12 months anal calibre, of 14.1 ± 2.72 (P < 0.0001). Statistically significant improvement in both Cleveland Clinic Incontinence Score and Obstructed Defaecation Syndrome Score was observed in all patients at 12 months. The overall success rate was 96% (48/50 patients). CONCLUSION: The use of an MRF is a safe and suitable option for the treatment of moderate and severe AS. The possibility of tailoring the flap, based on the degree as well as the level of AS, is the key.

Thrombotic complications in inflammatory bowel diseases.

Inflammatory bowel disease (IBD), Crohn's Disease (CD) and Ulcerative Colitis (UC) are associated with an increased risk of arterial and venous thromboembolism. A 2 to 3 time fold increased risk of developing thromboembolic complications was reported for IBD patients compared to general population. A systematic literature search was conducted using PubMed, Medline, Scopus, Cochrane database. The key words were: "Inflammatory Bowell Disease", "Crohn's Disease and Thrombosis", "Ulcerative Colitis and Thrombosis", "Thrombosis" and "Inflammatory Bowel Diseases and Thrombosis". Full articles and abstracts were included. Studies such as case reports, letters and commentaries were excluded from the analysis if appropriate data could not be extracted. Although no randomized controlled trials (RCTs) have been established to evaluate the efficacy of thromboprophylaxis in patients with IBD due to the incidence of VTE and PE in such patients, it is highly recommended the adoption of thromboprophylactic measures. Available prophylaxis and treatment options include pharmacological anticoagulant therapy (LMWH-Low Molecular Weight Heparin, Fondaparinux and UH-Unfractionated Heparin) and mechanical prophylaxis. In case of acute VTE patient must be treated with fibrinolytic agents and in selected non-responsive cases vascular surgery. IBD patients have an increased risk of VTE complications. Prophylaxis for VTE should be recommended in all patients who do not show contraindications to treatment.

Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signalling.

3-M syndrome is a primordial growth disorder caused by mutations in CUL7, OBSL1 or CCDC8. 3-M patients typically have a modest response to GH treatment, but the mechanism is unknown. Our aim was to screen 13 clinically identified 3-M families for mutations, define the status of the GH-IGF axis in 3-M children and using fibroblast cell lines assess signalling responses to GH or IGF1. Eleven CUL7, three OBSL1 and one CCDC8 mutations in nine, three and one families respectively were identified, those with CUL7 mutations being significantly shorter than those with OBSL1 or CCDC8 mutations. The majority of 3-M patients tested had normal peak serum GH and normal/low IGF1. While the generation of IGF binding proteins by 3-M cells was dysregulated, activation of STAT5b and MAPK in response to GH was normal in CUL7(-/-) cells but reduced in OBSL1(-/-) and CCDC8(-/-) cells compared with controls. Activation of AKT to IGF1 was reduced in CUL7(-/-) and OBSL1(-/-) cells at 5 min post-stimulation but normal in CCDC8(-/-) cells. The prevalence of 3-M mutations was 69% CUL7, 23% OBSL1 and 8% CCDC8. The GH-IGF axis evaluation could reflect a degree of GH resistance and/or IGF1 resistance. This is consistent with the signalling data in which the CUL7(-/-) cells showed impaired IGF1 signalling, CCDC8(-/-) cells showed impaired GH signalling and the OBSL1(-/-) cells showed impairment in both pathways. Dysregulation of the GH-IGF-IGF binding protein axis is a feature of 3-M syndrome.