The early detection of Salla disease through second-tier tests in newborn screening: How to face incidental findings

We describe here a 34 months child, practically asymptomatic which presented with high levels of free sialic acid in urine by biochemical detection in second-tier tests newborn screening and with two disease causing mutations in SLC17A5 gene. SLC17A5 mutation analysis showed p.Tyr306* previously decribed and the novel mutation p.Leu167Pro. This early onset diagnosis allowed us to perform a fast and accurate genetic counseling to the family, helped to better understanding the natural history of this rare disease and probably it could promote cost reduction in future diagnostic tests in the hypothetic case of starting symptoms without diagnosis established. Moreover, an early diagnosis could save family from a long period of time until achieving a definitive diagnostic and to develop an early symptomatic and supportive management of patient to attenuate, as much as possible, disease complications. But, above all, this case illustrates the huge ethical dilemma which arises from any secondary finding (second tier) in newborn screening.     

EUS-guided cholecystostomy versus endoscopic transpapillary cholecystostomy for acute cholecystitis in high-risk surgical patients

1. Download high-res image (287KB)
2. Download full-size image

     

Hilar cholangiocarcinoma: resectability and radicality after routine diagnostic imaging

Background/Purpose En-bloc resection has contributed to the improvement of long-term survival in patients with hilar cholangiocarcinoma. In addition, attenuation of intraoperative traumatization of the tumor may decrease tumor spread. The objective of this study was to assess the importance of a routine diagnostic workup for the surgical strategy, radicality, and results in patients with hilar cholangiocarcinoma.Methods Between September 1997 and December 2002, 82 patients with hilar cholangiocarcinoma were treated at our department. Preoperative diagnostic workup included endoscopic retrograde cholangiography (ERC), percutaneous transhepatic cholangiography (PTC), computed tomography (CT), and magnetic resonance imaging (MRI). The results of preoperative and retrospective (blinded) assessment of diagnostic data concerning the tumor growth along the bile ducts were compared with the results of surgery.Results The resection rate was 75%, and the hospital mortality, 7%. The prospective assessment of the resection to be performed was correct in 81% of cases. In ERC, magnetic resonance cholangiography (MRC), and PTC, tumor assessment was precise in 29%, 36%, and 53%, of cases, respectively. Overestimation occurred more frequently than underestimation. The 3-year survival of patients with formally curative or palliative en-bloc resection was 61% and 15%, respectively. For the 9 patients with hilar resection, the 3-year survival was 25%. Survival of patients was comparable, regardless of whether their tumor had been correctly assessed or over- or underestimated. In the multivariate analysis, R0 resection was the only significant prognostic factor (P = 0.011).Conclusions Our routine diagnostic approach led to high resection and survival rates. Obviously a sophisticated diagnostic workup is not an absolute prerequisite for adequate surgery.     

Dural venous sinus stenting for idiopathic intracranial hypertension: An updated review

Background

Dural venous sinus stenting (DVSS) is an accepted treatment option in selected patients with medically refractory idiopathic intracranial hypertension and obstructive venous outflow physiology prior to cerebrospinal flow diversion (CSFD) surgery. There are no randomized controlled studies focusing on outcomes and complication rates for dural venous sinus stenting.

RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas

de Vries M M, Celestino R, Castro P, Eloy C, Máximo V, van der Wal J E, Plukker J T M, Links T P, Hofstra R M W, Sobrinho‐Simões M & Soares P
(2012) Histopathology  61, 833–843 RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas Aims: The molecular alterations underlying follicular Hürthle cell carcinomas (FHCCs) are largely unknown. In an attempt to clarify this issue, we analysed a series of Hürthle cell tumours for the presence of RET/PTC and PAX8/PPARG rearrangements and BRAF, HRAS and NRAS mutations. Methods and results: We investigated a series of 20 follicular Hürthle cell tumours [17 FHCCs and three follicular Hürthle cell adenomas (FHCAs)]. RET/PTC rearrangements were found in 33% of FHCAs and in 38% of FHCCs. All RET/PTC‐positive FHCCs had a solid pattern of growth. PAX8/PPARG rearrangement was present in 27% of the FHCCs which displayed, in most cases, a follicular architecture. NRAS mutation was detected in one FHCC. An FHCC with a solid/microfollicular growth pattern scored positive for both RET/PTC and PAX8/PPARG rearrangement. Conclusions: Our study has shown a significant association between RET/PTC rearrangements and FHCCs with a solid growth pattern, thus raising the possibility of using tyrosine kinase inhibitors for the treatment of patients with FHCCs, which are often refractory to radioiodine treatment.     

RET/PTC rearrangement in thyroid tumors

Rearrangement of the RET gene, also known as RET/PTC rearrangement, is the most common genetic alteration identified to date in thyroid papillary carcinomas. The prevalence of RET/PTC in papillary carcinomas shows significant geographic variation and is approx 35% in North America. RET/PTC is more common in tumors in children and young adults, and in papillary carcinomas associated with radiation exposure. There are at least 10 different types of RET/PTC, all resulting from the fusion of the tyrosine kinase domain of RET to the 5′ portion of different genes. RET/PTC1 and RET/PTC3 are the most common types, accounting for >90% of all rearrangements. There is some evidence that different types of RET/PTC may be associated with distinct biologic properties of papillary carcinomas. RET/PTC1 tends to be more common in tumors with typical papillary growth and microcarcinomas and to have a more benign clinical course, whereas RET/PTC3 in some populations shows a strong correlation with the solid variant of papillary carcinoma and more aggressive tumor behavior. RET/PTC has recently been found in hyalinizing trabecular adenomas of the thyroid gland, providing molecular evidence in favor of this tumor to be a variant of papillary carcinoma. The occurrence of RET/PTC in Hashimoto thyroiditis and thyroid follicular adenomas and hyperplastic nodules reported in several studies has not been confirmed in other observations and remains controversial.     

A new BRAF gene mutation detected in a case of a solid variant of papillary thyroid carcinoma

BRAF gene mutations have been frequently detected in papillary thyroid carcinoma (PTC). Moreover, there is a close association between the type of mutation and the PTC histotype: BRAF(V600E) is associated with conventional PTC and with histological variants of PTC displaying a prominent papillary growth pattern, whereas BRAF(K601E) is associated with the follicular variant of PTC. We report the detection of a novel BRAF triplet deletion in a case of PTC displaying a predominantly solid growth pattern. The deletion leads to the replacement of a valine and a lysine by a glutamate in the BRAF activation segment (BRAF(VK600-1E)), thus mimicking partially the 2 BRAF mutations previously described. Our study reinforces the existence of a close relationship between the occurrence of some types of BRAF mutation and some PTC histotypes. The genetic study of more cases of the solid variant of PTC is necessary to find whether there exists a significant association between the occurrence of BRAF(VK600-1E) and such PTC histotype.