Prophylactic thyroidectomy in children with multiple endocrine neoplasia type 2

Background In patients with multiple endocrine neoplasia type 2 (MEN2) syndrome, genetic testing offers early diagnosis, stratifies the risk of developing medullary thyroid cancer (MTC) and informs the timing of thyroidectomy. The efficacy of treatment, which depends on timely and safe surgery, is not well established. Methods This was a retrospective review of diagnostic and clinicopathological outcomes of prophylactic thyroidectomy in children with MEN2 between 1995 and 2013 in the UK. American Thyroid Association (ATA) 2009 guidelines were used as a benchmark for adequate treatment. Results Seventy‐nine children from 16 centres underwent total thyroidectomy. Thirty‐eight patients (48 per cent) underwent genetic testing and 36 (46 per cent) had an operation performed above the age recommended by the ATA 2009 guidelines; pathology showed MTC in 30 patients (38 per cent). Late surgery, above‐normal preoperative calcitonin level and MTC on pathology correlated with late genetic testing. Twenty‐five children had lymphadenectomy; these patients had more parathyroid glands excised (mean difference 0·61, 95 per cent c.i. 0·24 to 0·98; P = 0·001), and were more likely to have hypocalcaemia requiring medication (relative risk (RR) 3·12, 95 per cent c.i. 1·54 to 6·32; P = 0·002) and permanent hypoparathyroidism (RR 3·24, 1·29 to 8·11; P = 0·010) compared with those who underwent total thyroidectomy alone. Age did not influence the development of complications. Conclusion Late genetic testing may preclude age‐appropriate surgery, increasing the risk of operating when MTC has already developed. Early genetic testing and age‐appropriate surgery may help avoid unnecessary lymphadenectomy and improve outcomes

The critical view of safety during laparoscopic cholecystectomy: Strasberg Yes or No? An Italian Multicentre study

Background: Laparoscopic cholecystectomy is considered the gold standard for the treatment of gallbladder lithiasis; nevertheless, the incidence of bile duct injuries (BDI) is still high (0.3–0.8%) compared to open cholecystectomy (0.2%). In 1995, Strasberg introduced the "Critical View of Safety" (CVS) to reduce the risk of BDI. Despite its widespread use, the scientific evidence supporting this technique to prevent BDI is controversial. Methods: Between March 2017 and March 2019, the data of patients submitted to laparoscopic cholecystectomy in 30 Italian surgical departments were collected on a national database. A survey was submitted to all members of Italian Digestive Pathology Society to obtain data on the preoperative workup, the surgical and postoperative management of patients and to judge, at the end of the procedure, if the isolation of the elements was performed according to the CVS. In the case of a declared critical view, iconographic documentation was obtained, finally reviewed by an external auditor. Results: Data from 604 patients were analysed. The study population was divided into two groups according to the evidence (Group A; n = 11) or absence (Group B; N = 593) of BDI and perioperative bleeding. The non-use of CVS was found in 54.6% of procedures in the Group A, and 25.8% in the Group B, and evaluating the operator-related variables the execution of CVS was associated with a significantly lower incidence of BDI and intraoperative bleeding. Conclusions: The CVS confirmed to be the safest technique to recognize the elements of the Calot triangle and, if correctly performed, it significantly impacted on preventing intraoperative complications. Additional educational programs on the correct application of CVS in clinical practice would be desirable to avoid extreme conditions that may require additional procedures

Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy

Enhanced intrarenal renin-angiotensin system (RAS) is implicated in the development and progression of renal injury. To investigate whether angiotensinogen (AGT) expression is involved in glomerular RAS activity and glomerular injury, we examined glomerular AGT expression and its correlation with expression of other RAS components, and levels of glomerular injury in samples from patients with immunoglobulin A nephropathy (IgAN) (23) and minor glomerular abnormalities (MGA) (8). Immunohistochemistry showed that AGT protein was highly expressed by glomerular endothelial cells (GEC) and mesangial cells in nephritic glomeruli of IgAN compared with glomeruli of MGA. Levels of glomerular AGT protein were well correlated with levels of glomerular angiotensin II (ang II), transforming growth factor-β (TGF-β), α-smooth-muscle actin, glomerular cell number, and glomerulosclerosis score but not with those of glomerular angiotensin-converting enzyme and ang II type 1 receptor. Real-time polymerase chain reaction (RT-PCR) and Western blot analyses using cultured human GEC indicated that ang II upregulated AGT messenger ribonucleic acid (mRNA) and protein expression in a dose- and time-dependent manner. These data suggest that activated glomerular AGT expression is likely involved in elevated local ang II production and, thereby, may contribute to increased TGF-β production and development of glomerular injury in IgAN. Augmentation of GEC-AGT production with ang II stimulation might drive further glomerular injury in a positive-feedback loop

Anti-carbamylated protein antibodies in patients with systemic sclerosis: an intriguing association with skin involvement

Background Systemic sclerosis (SSc), one of the most complex connective tissue disease, is characterized by three pathogenic events namely, vascular damage, autoimmunity and fibroblast activation, leading to a widespread fibrosis of skin and internal organs (1,2). Previous studies showed that 1) carbamylation mainly affects structural proteins undergoing to a low turn-over rate, namely dermal skin and tendons-associated proteins; and that 2) carbamylated proteins accumulate in skin in an age-dependent manner, contributing to tissue alteration (3). Objectives As dermis is a disease target and anti-carbamylated protein antibodies (anti-CarP Ab) have been reported in patients with SSc (4), we sought to evaluate any relationship between anti-CarP Ab and clinical parameters reflecting skin involvement in SSc. Methods Serum samples and clinical data from 123 patients with SSc were collected. Anti-CarP Ab were detected by indirect ELISA, using carbamylated bovine serum albumin as the antigen. Serum Anti-CarP Ab levels were also measured in 41 healthy aged-matched individuals. Clinical data were retrieved as previously reported (5). Results The mean serum levels of anti-CarP Ab did not statistically differ between healthy and SSc group. In SSc, Spearman analysis showed that anti-CarP inversely correlated with the modified Rodnan skin score (RSS) (R= -0.325, p<0.001), independently of patients' age. Receiver operating characteristics (ROC) analysis identified the anti-CarP cutoff that best discriminated dichotomized clinical variables related to skin involvement. This cutoff that was employed to subdivide SSc patients into anti-CarP positive and anti-CarP negative patients. Three SSc skin-related clinical parameters were significantly different between groups: RSS (p=0.001), SI skin (p=0.002), and scleredema (p<0.001). A worse skin involvement was associated with low anti-CarP levels. Conclusions The study shows that anti-CarP Ab serum level inversely associates to the severity of skin involvement in SSc patients. One possible mechanism to explain the inverse association is that the disease-dependent accumulation of carbamylated proteins in the skin may neutralize circulating anti-CarP Ab, thus contributing to their serum levels decrease. However, further investigation is needed to clarify this issue and to assess whether the levels anti-CarP Ab can be useful in the clinical setting of SSc

[Video-assisted thyroidectomy with minimally invasive central cervicotomy: initial experience in an endocrine surgery division]

Abstract Minimally invasive video-assisted thyroidectomy, a recently developed technique, has been shown to be feasible and safe. Nevertheless, to obtain the best results, the surgeon should be well trained in endoscopic surgery. We attempted to answer the question whether an endocrine surgery division with no previous experience in endoscopic neck surgery could easily import the new technique. The inclusion criteria were nodules < or = 3.5 cm diameter or thyroid lobe volume less than 15 ml, and no thyroiditis or previous neck surgery. Suspect malignant nodules were excluded. The procedure was carried out through a 20 to 30 mm central neck incision, with external retraction and no neck insufflation. The vessels were ligated or closed by means of clips. From March 2004 to March 2005, 127 thyroidectomies were performed, of which 36 were thyroid lobectomies. Of these, 12 lobectomies by minimally invasive video-assisted thyroidectomy were performed for monolateral goiter (4 left, 8 right). There were no intraoperative complications. No recurrent laryngeal nerve palsy or permanent hypoparathyroidism occurred. The mean operative time was 74.4 min (median: 70; range: 45-115). The results, in terms of patient comfort, reduced postoperative pain and cosmetic quality were excellent. The technique allowed careful assessment of the inferior and superior laryngeal nerve. Thorough haemostasis was aided by the magnification of the image and optimal illumination. The learning curve appeared short, owing probably to previous experience in conventional endocrine surgery and the closer similarities of minimally invasive video-assisted thyroidectomy to enhanced-view conventional surgery than to laparoscopic surgery. In our experience the clinical impact was limited as a result of the small percentage of patients fulfilling the strict inclusion criteria