Risk of incident Mycobacterium tuberculosis infection in patients with inflammatory bowel disease: a nationwide population-based study in South Korea.

BACKGROUND: The low incidence of Mycobacterium tuberculosis infection and lack of adequate controls have prevented researchers from estimating tuberculosis (TB) risk in inflammatory bowel disease (IBD) patients. AIM: To evaluate the risk of incident TB among IBD patients. METHODS: Using the 2011-2013 data of the South Korean National Health Insurance (NHI) system, we calculated the incidence rates (IRs), standardised incidence ratio (SIR) and number needed to screen (NNS) for incident TB in IBD patients compared to the general population in terms of subtype, age, gender and IBD medications. RESULTS: The IR, SIR and NNS for TB in IBD patients were 223.9/100 000 person-years, 2.64 (2.30-3.01) and 446.6 (392.8-517.6), respectively. The TB IR in Crohn's disease (CD) patients was significantly higher than that in ulcerative colitis (UC) patients (340.1/100 000 person-years vs. 165.5/100 000 person-years, respectively; P < 0.001). The SIR and NNS for TB among CD patients were 4.00 (3.59-4.45) and 604.2 (506.1-749.6), respectively; those among UC patients were 1.95 (1.66-2.27) and 294.0 (246.9-363.4). The TB IRs in IBD patients did not differ significantly by age or gender (Ptrend  = 0.505 and P = 0.861, respectively). The TB IRs among IBD patients prescribed 5-ASA, corticosteroids, immunomodulators and anti-TNF-α were 143.5, 208.5, 284.6 and 554.1 per 100 000 person-years, respectively. Among IBD patients treated using anti-TNF-α, the TB IR was significantly higher than that among all IBD patients (P < 0.001); the SIR and NNS for TB were 6.53 (5.99-7.09) and 180.5 (144.6-240.1) respectively. CONCLUSION: Clinicians should be aware of the increased risk of active tuberculosis in patients with IBD who are receiving anti-TNF-α therapy.

Percutaneous radiofrequency ablation for symptomatic uterine leiomyomas: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) in the treatment of uterine leiomyomas. MATERIALS AND METHODS: Medline, Embase, and Cochrane databases were searched through August 2014 for all relevant studies on RFA for uterine leiomyomas. The efficacy and safety of RFA were assessed using the outcome measures of tumor volume, symptom severity score, health-related quality of life (HRQL) score, procedure-related complications, and reintervention. The authors calculated pooled event rates with 95% confidence intervals using random-effects model to assess the effects of RFA. RESULTS: Eight observational studies were identified as eligible for inclusion in this meta-analysis and included 370 patients. All analyzed outcomes showed statistically significant improvements from baseline to final follow-up. Twenty-seven complications were identified and five of them qualified as major complications. Five patients required reintervention after RFA. CONCLUSIONS: Percutaneous RFA is an effective and safe treatment for patients with uterine leiomyomas.

Correlation between 99mTc-pertechnetate uptakes and expressions of human sodium iodide symporter gene in breast tumor tissues.

We investigated a correlation between the expression of human sodium iodide symporter (hNIS) mRNA and the uptake of 99mTc-pertechnetate in 25 breast tumors. 99mTc-pertechnetate scintigraphy revealed positive uptake in 4 patients. The normalized mRNA expression of hNIS was higher in tumors with positive uptake on the scintigraphy (n=4, median 0.97, range 0.78-1.27) than that in negative uptake tumors (n=21, median 0.46, range 0.10-1.03, p < 0.005). 99mTc-pertechnetate uptake is correlated with the hNIS expression in the breast tumor.

Growth inhibition and chemosensitivity of poorly differentiated human thyroid cancer cell line (NPA) transfected with p53 gene.

BACKGROUND: We investigated whether retroviral p53 transfection could enhance growth inhibition and chemosensitivity in a p53 mutant papillary thyroid cancer cell line (NPA). METHODS: NPA cells were transfected with either LXSN/p53 or mock infection in the presence of Adriamycin. Gene expression was confirmed by western blotting. Nude mice were injected subcutaneously with NPA cells after transfection with either LXSN/p53 or mock infection on opposite sides, and the tumor growth was compared. RESULTS: There was a dose-dependent inhibition of tumor growth with LXSN/p53 transfection. Tumor growth was inhibited more by p53 gene transfection relative to mock transfection in the presence of Adriamycin. CONCLUSION: These treatment modalities could be beneficial in the treatment of p53 mutant positive thyroid cancers.

F-18-fluorodeoxyglucose positron emission tomography as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients with local recurrence in cervical lymph nodes.

BACKGROUND: F-18-labeled fluorodeoxyglucose-positron emission tomography (FDG-PET) has a supplementary role in localizing recurrent sites of differentiated thyroid carcinoma. We evaluated whether FDG-PET is feasible as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients. METHODS: Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 22 papillary thyroid patients. All patients had thyroidectomy and I-131 ablation therapy beforehand and showed negative I-131 scans on follow-up studies. RESULTS: In 85 cervical lymph node groups dissected, 56 lymph node groups revealed metastasis. The sensitivity and specificity of FDG PET for metastasis were 80% (45 of 56) and 83% (24 of 29), respectively. Among the pathologically positive 33 lymph nodes with normal size(< or =1 cm), FDG-PET detected 23 nodes. Serum thyroglobulin levels were elevated in 12 patients (sensitivity, 55%). CONCLUSION: FDG-PET accurately detected the recurred cervical lymph nodes of differentiated thyroid carcinoma patients who showed negative I-131 scan. FDG-PET is suitable for the presurgical evaluation of these patients.

Expressions of human sodium iodide symporter mRNA in primary and metastatic papillary thyroid carcinomas.

The sodium iodide symporter (NIS) is a plasma membrane protein that is responsible for iodide transport into thyroid cells. To understand the regulation and expression of human NIS (hNIS) in papillary thyroid carcinomas, we evaluated the expression levels of hNIS mRNA in primary and lymph node metastatic papillary carcinoma tissues. The correlation of mRNA levels between hNIS and thyroid-specific genes, thyrotropin (TSH) receptor, and thyroglobulin (Tg), were also investigated. Twenty-three cases of papillary carcinoma and 7 pairs of primary and lymph node metastastic tissues were included in this study. We measured the expression levels of hNIS, TSH receptor, and Tg mRNAs by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA). The levels of hNIS mRNA in lymph node metastatic tissues were evaluated by RT-PCR. By semiquantitative RT-PCR, 87% of papillary carcinoma (20/23) expressed hNIS mRNA, but the degrees of expression were variable and were lower than those of normal thyroid tissues. The decreased expression of hNIS mRNA in papillary carcinoma compared to normal thyroid tissue was also noticed by RPA. All 23 papillary carcinomas in this study showed the expression of TSH receptor and Tg mRNAs. The levels of TSH receptor mRNA were again lower in papillary thyroid carcinomas than in normal controls. The level of hNIS mRNA was correlated with the levels of TSH receptor (r = 0.449, p < 0.05), but not with Tg mRNA. In addition, significant correlation of mRNA level was observed between TSH receptor and Tg (r = 0.706, p < 0.01). Two of six lymph node metastatic tissues did not show hNIS mRNA even with significant hNIS expressions in papillary carcinoma tissues in thyroid. The levels of hNIS expression of the remaining four lymph node metastatic tissues were lower than those of corresponding primary tissues. Interestingly, one case showed no hNIS expression in primary tissue, but significant hNIS expression in lymph node metastatic tissue. No correlation was found in hNIS mRNA expression between primary and lymph node metastatic tissues. Our results suggest that the measurements of hNIS mRNA level in primary tissues may not predict the therapeutic response to radioactive iodine.

Sonographically guided ethanol sclerotherapy for benign thyroid cysts: results in 22 patients.

OBJECTIVE: We evaluate the efficacy and safety of sonographically guided ethanol sclerotherapy for benign thyroid cysts. SUBJECTS AND METHODS: We examined 22 patients with benign thyroid cysts (13 complex cysts and nine pure cysts) confirmed by fine-needle aspiration biopsy. Sonographically guided aspiration of the cystic fluid was followed by instillation of absolute ethanol (99.9%) into the cystic cavity: the injected volume of ethanol was 40-100% of the volume of fluid aspirated. The procedure was performed every 1 or 3 months for one or two sessions (mean, 1.2 sessions). Follow-up sonography was performed 1-10 months after the final session, and we observed patients after ethanol sclerotherapy for complications. RESULTS: The initial volume of the cysts ranged from 3.5 to 42 ml. In 21 patients, the volume of the cyst decreased or the cyst was obliterated. The volume of the cyst was reduced by 50-99% in 13 patients and by 1-49% in six patients, and the cyst was obliterated in two patients. In one patient, the volume of the cyst increased. The volume of ethanol instilled was significantly correlated with the volume reduction rate of the cyst. There was a difference in the volume reduction rate between patients in whom 10 ml or more of initial volume was used and those in whom less than 10 ml of initial volume was used; that is, the volume reduction rate of the group with the initial cyst volume of more than 10 ml was higher than that of the other group. Important long-standing and severe complications were not observed. CONCLUSION: Sonographically guided ethanol sclerotherapy is a safe and effective tool for the therapy of benign thyroid cysts.

Prevalences of Gs alpha, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population.

OBJECTIVE: In thyroid tumours, ras, Gs alpha, p53 mutations and ret/PTC rearrangement have been reported with variable prevalences in different geographical regions. We studied the prevalence of these mutations and rearrangement in thyroid tumours in a Korean population. As MDM2 and Bcl-1 protein expressions have been suggested to be associated with p53 protein, we also studied possible relationships among them. PATIENTS AND DESIGN: Eleven cases of adenomatous goitre, eight cases of follicular adenoma, five cases of follicular carcinoma and 37 cases of papillary carcinoma were included in this study. To find mutations and rearrangement, RT-PCR, SSCP and/or direct sequencing, after subcloning if necessary, were used, and immunohistochemical stainings were performed for p53, MDM2 and Bcl-2 proteins in cases of papillary carcinoma. RESULTS: We could not find any rearrangement for ret/PTC-1, -2, -3 and mutation of Gs alpha. For the ras oncogene, K and H-ras mutations were not found, but N-ras mutations, point mutation of CAA to CGA in codon 61, were detected in one follicular adenoma (12.5%, 1/8) and one follicular carcinoma (33%, 1/3). p53 mutations were detected in only one case of papillary carcinoma (3%, 1/31: exon 8, codon 266 GGA-->GAA). In 30 cases of papillary carcinoma without p53 mutation, the prevalences of positive immunohistochemical staining were 13.3% for p53 protein, 53.3% for MDM2 protein and 56.7% for Bcl-2 protein. While over-expression of p53 protein was not significantly related to that of MDM2 and Bcl-2 proteins, over-expression of MDM2 and Bcl-2 in papillary carcinoma were associated. CONCLUSION: ret/PTC rearrangement, Gs alpha, ras and p53 mutations are relatively rare in differentiated thyroid neoplasms from a Korean population, which may reflect genetic and environmental differences from patients in countries with high prevalences. P53 protein over-expression was noted in 13.3% of papillary carcinoma cases without p53 mutation and was not significantly related to MDM2 and Bcl-2 expression.

In vivo genomic footprinting of thyroid hormone-responsive genes in pituitary tumor cell lines.

We studied the effects of thyroid hormone (T3) on nuclear protein-DNA interactions by using dimethyl sulfate (DMS) and DNase I ligation-mediated PCR footprinting. We examined an endogenous gene the growth hormone (GH) gene, and a stably transfected plasmid containing the chicken lysozyme silencer (F2) T3 response element (TRE) gene, F2-TRE-TK-CAT, both in pituitary tumor (GC) cells. The 235-1 cell line, which expresses prolactin (PRL) and Pit-1, but not the T3 receptor (TR) or GH, was used as a control. DMS and DNase I footprinting identified protected G residues in the Pit-1, Sp1, and Zn-15 binding sites of the GH gene in GC, but not in 235-1, cells. There was no specific protection of the tripartite GH TRE at -180 bp against either DMS or DNase I in the absence or presence of T3 in either cell line. However, T3 increased protection of the Pit-1 and Sp1 binding sites against DMS in GC cells. In GC cells stably transfected with a plasmid containing F2-TRE-TK-CAT or TRalpha, chloramphenicol acetyltransferase expression was T3 inducible and DMS footprinting revealed both F2 TRE TR-binding half sites in a pattern suggesting the binding of TR homodimers before and during T3 exposure. We conclude that the GH gene is accessible to specific nuclear proteins in GC, but not in 235-1, cells and that T3 enhances this interaction, although there is no evidence of TR binding to the low-affinity rat GH TRE. The presence of TR binding to the high-affinity F2 TRE before and during T3 exposure suggests that reversible interaction of T3 with DNA-bound TRs, rather than transient T3-TR contact with TREs, determines the level of T3-stimulated transcriptional activation.