Long-term ultrasound follow-up of intrathyroidal ectopic thymus in children.

OBJECTIVE: To present the sonographic follow-up of intrathyroidal ectopic thymus (IET) in children and adolescent patients. PATIENTS: Out of the 507 children referred to FNAB between 2006 and 2018, 30 (5.9%) pediatric patients (10 females), mean age 5.7 years (1.2-13.8, median 4.9 years) were diagnosed with IET. METHODS: A retrospective analysis of medical files of patients diagnosed with IET between 2006 and 2018. Assessed data included ultrasound characterisation, elastographic strain ratio (SR) results and hormonal evaluation. RESULTS: Analysis of thyroid US scans revealed that the mean age at the first thyroid ultrasound was 5.7 (1.2-13.8, median 4.9) years, and at the last US 10.7 (3.7-18, median 10.5) years. The mean time of the IET observation was 59.6 (2-148, median 53.5) months. On US, IET was hypoechoic with multiple linear and punctate echoes, hypovascular, fusiform on longitudinal plane and round or polygonal on an axial plane, more common in the right thyroid lobe (66.7%) and located in the posterior part of the lobes (54.5%), bilateral in two patients and multifocal in one patient. SR of IET was similar to the surrounding normal thyroid tissue. Complete regression of IET was observed in 12/30 patients after a mean time of 81.7 months (median 76.5), at the mean age of 13.7 (9.2-18, median 13.9) years. FNAB was performed in 10/30 and a hemithyroidectomy in 1/30 IET patients. In the FNAB (+) group, patients were younger (5.08 vs 6.08 years) and lesions were larger (0.12 ml vs 0.05 ml) than in the FNAB (-) group. All patients with IET were euthyroid with negative TPOAb and TgAb levels. CONCLUSION: The reproducibility of unique ultrasound features of IETs allows for safe long-term follow-up of these benign lesions in the majority of pediatric patients: not only monitoring the regression of IET but also screening towards the rare occurrence of a tumor arising from the IET.

Follow-up of parenchymal changes in the thyroid gland with diffuse autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma.

PURPOSE: To present the outcomes of ultrasound (US) follow-ups in children with autoimmune thyroid disease who did not have a thyroid nodule on admission but developed papillary thyroid carcinoma (PTC) and to characterize the parenchymal changes in the thyroid gland prior to the development of PTC. METHODS: A retrospective thyroid US scan review of 327 patients diagnosed with AIT was performed. Forty patients (40/327, 12.2%) presented nodular AIT variant with a normoechogenic background. Eleven patients (11/327, 3.4%, 11/40, 27.5%) presenting this variant were diagnosed with PTC (nine females-mean age 15.3 years; two males aged 11 and 13 years). In five of 11 patients, the suspicious nodule that was later confirmed to be PTC was detected on the initial US at presentation. For the remaining six females (6/11) who developed PTC during the follow-up, we retrospectively analysed their US thyroid scans and these patients were selected for analysis in this study. RESULTS: On admission, the US evaluation revealed an enlarged normoechogenic thyroid gland in three patients and a hypoechogenic thyroid gland with fibrosis as indicated by irregular, chaotic hyperechogenic layers in three patients. No thyroid nodules were identified. Ultrasound monitoring revealed increasing echogenicity of the thyroid parenchyma during the follow-up. PTC developed in a mean time of 4.6 years (1 9/12-7 4/12 years) since referral to the outpatient thyroid clinic and 2.9 years (6/12-6 9/12) since the last nodule-free US thyroid scan. CONCLUSIONS: Sonographic follow-up assessments warrant further exploration as a strategy to determine PTC susceptibility in the paediatric population.

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development.

BACKGROUND: The prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3-43%. OBJECTIVE: To investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients. PATIENTS: 179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females). METHODS: Retrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed. RESULTS: Analysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%-diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%-diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%-micronodulations and in 3.9%-diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background. CONCLUSION: Patients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

The decreased metastatic potential of rhabdomyosarcoma cells obtained through MET receptor downregulation and the induction of differentiation.

Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. The MET receptor has an important role in the biology of RMS, and its overexpression and hyperactivation correlate with the metastatic ability of RMS. Consequently, interfering with MET expression or functionality may constitute a sound strategy for reducing the progression and metastatic potential of RMS. Our study reveals that downregulation of the MET receptor leads to changes in the morphology of ARMS cell in vivo. Tumors acquire a spindle shape that is characteristic of muscle fibers. Inhibition of MET expression or function leads to (i) a decreased expression of the early myogenic marker MyoD, (ii) a decreased ability of ARMS cells to metastasize to bone marrow cavities, (iii) downregulation of CXCR4 receptor expression and (iv) a decreased migration of MET-depleted cells towards gradients of HGF and SDF-1. Finally, we demonstrate that in vitro differentiation of alveolar RMS cells decreases their metastatic behavior by reducing both the expression of the MET and CXCR4 receptors and their migratory response to HGF and SDF-1. These findings suggest that blockers of MET receptor function and inducers of RMS cells differentiation may be clinically useful for reducing the aggressiveness and metastatic potential of RMS and may have significant implications for its treatment.

The effects of preoperative chemotherapy on isolated tumour cells in the blood and bone marrow of gastric cancer patients.

Recent studies in breast cancer suggest that monitoring the isolated tumour cells (ITC) may be used as a surrogate marker to evaluate the efficacy of systemic chemotherapy. In the present study, we have investigated the effects of preoperative chemotherapy on ITC in the blood and bone marrow of patients with potentially resectable gastric cancer. After sorting out the CD45-positive cells, the presence of ITC defined as cytokeratin-positive cells was examined before and after preoperative chemotherapy. The patients received two courses of preoperative chemotherapy with cisplatin (100 mg m(-2), day 1) and 5-fluorouracil (1000 mg m(-2), days 1-5), administered every 28 days. Fourteen of 32 (44%) patients initially diagnosed with ITC in blood and/or bone marrow were found to be negative (responders) after preoperative chemotherapy (P<0.01). The incidence of ITC in bone marrow was also significantly (P<0.01) reduced from 97 (31 of 32) to 53% (17 of 32). The difference between patients positive for ITC in the blood before (n=7, 22%) and after (n=5, 16%) chemotherapy was statistically insignificant. The overall 3-year survival rates were 32 and 49% in the responders and non-responders, respectively (P=0.683). These data indicate that preoperative chemotherapy can reduce the incidence of ITC in patients with gastric cancer.

Chlorination of N-acetyltyrosine with HOCl, chloramines, and myeloperoxidase-hydrogen peroxide-chloride system.

N-acetyl-L-tyrosine (N-acTyr), with the alpha amine residue blocked by acetylation, can mimic the reactivity of exposed tyrosyl residues incorporated into polypeptides. In this study chlorination of N-acTyr residue at positions 3 and 5 in reactions with NaOCl, chloramines and the myeloperoxidase (MPO)-H2O2-Cl- chlorinating system were invesigated. The reaction of N-acTyr with HOCl/OCl- depends on the reactant concentration ratio employed. At the OCl-/N-acTyr (molar) ratio 1:4 and pH 5.0 the chlorination reaction yield is about 96% and 3-chlorotyrosine is the predominant reaction product. At the OCl-/N-acTyr molar ratio 1:1.1 both 3-chlorotyrosine and 3,5-dichlorotyrosine are formed. The yield of tyrosine chlorination depends also on pH, amounting to 100% at pH 5.5, 91% at pH 4.5 and 66% at pH 3.0. Replacing HOCl/OCl- by leucine/chloramine or alanine/chloramine in the reaction system, at pH 4.5 and 7.4, produces trace amount of 3-chlorotyrosine with the reaction yield of about 2% only. Employing the MPO-H2O2-Cl- chlorinating system at pH 5.4, production of a small amount of N-acTyr 3-chloroderivative was observed, but the reaction yield was low due to the rapid inactivation of MPO in the reaction system. The study results indicate that direct chlorination of tyrosyl residues which are not incorporated into the polypeptide structure occurs with excess HOCl/OCl- in acidic media. Due to the inability of the myeloperoxidase-H2O2-Cl- system to produce high enough HOCl concentrations, the MPO-mediated tyrosyl residue chlorination is not effective. Semistable amino-acid chloramines also appeared not effective as chlorine donors in direct tyrosyl chlorination.

Effects of humanization by variable domain resurfacing on the antiviral activity of a single-chain antibody against respiratory syncytial virus.

HNK20 is a mouse monoclonal IgA that binds to the F glycoprotein of respiratory syncytial virus (RSV) and neutralizes the virus, both in vitro and in vivo. The single-chain antibody fragment (scFv) derived from HNK20 is equally active and has allowed us to assess rapidly the effect of mutations on affinity and antiviral activity. Humanization by variable domain resurfacing requires that surface residues not normally found in a human Fv be mutated to the expected human amino acid, thereby eliminating potentially immunogenic sites. We describe the construction and characterization of two humanized scFvs, hu7 and hu10, bearing 7 and 10 mutations, respectively. Both molecules show unaltered binding affinities to the RSV antigen (purified F protein) as determined by ELISA and surface plasmon resonance measurements of binding kinetics (Ka approximately 1x10(9) M-1). A competition ELISA using captured whole virus confirmed that the binding affinities of the parental scFv and also of hu7 and hu10 scFvs were identical. However, when compared with the original scFv, hu10 scFv was shown to have significantly decreased antiviral activity both in vitro and in a mouse model. Our observations suggest that binding of the scFv to the viral antigen is not sufficient for neutralization. We speculate that neutralization may involve the inhibition or induction of conformational changes in the bound antigen, thereby interfering with the F protein-mediated fusion of virus and cell membranes in the initial steps of infection.

[Complications of endoscopic sphincterotomy]. / Powiklania endoskopowej papillotomii.

The aim of the study is an analysis of the complications among the patients who underwent endoscopic sphincterotomy. In years 1991-1996 in our Department 412 patients underwent endoscopic sphincterotomy. Bile ducts stones, acute bile pancreatitis, papilla Vateri stricture and the postoperative bile fistula were the indications for the procedure. Complications occurred in 37 patients (12 of them were operated on). One patient died due to duodenal perforation. GI bleeding, acute pancreatitis, common bile duct perforation, recurrence of the stricture and missing the concrement in the duct were the main complications. Endoscopic sphincterotomy remains the recommended method in describe cases.

Intranasal monoclonal IgA antibody to respiratory syncytial virus protects rhesus monkeys against upper and lower respiratory tract infection.

Respiratory syncytial virus (RSV), the major cause of lower respiratory tract disease in infants, is thought to infect the upper airways before spreading to the lower respiratory tract. A rhesus monkey model of RSV infection after upper airway inoculation was used to test the protective effect of intranasal treatment with HNK20, a mouse monoclonal IgA antibody against RSV F glycoprotein. HNK20 was administered once daily for 2 days before RSV challenge and 4 days after challenge. Treatment with 0.5 mg/kg HNK20 reduced viral shedding in the nose, throat, and lungs by 3-4 log10/mL (P < or = .002). All monkeys developed RSV neutralizing antibody in serum, even in the absence of detectable viral replication. Neutralizing concentrations of monoclonal antibody remained in nasal secretions for > 1 day after treatment. These results suggest that nose-drop application of monoclonal antibody could provide convenient and effective protection against RSV infection in human infants at risk of severe lower respiratory tract disease.