Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: pattern of nodal metastasis, morbidity, recurrence, and postoperative levels of serum parathyroid hormone

OBJECTIVE: To investigate the pattern of nodal metastasis, morbidity, recurrence rates of papillary thyroid carcinoma (PTC), and parathyroid hormone (PTH) responses following neck dissection (ND) plus total thyroidectomy (TT). SUMMARY BACKGROUND DATA: While hypoparathyroidism develops after TT plus ND, little is known of postoperative PTH response. METHODS: Of 155 PTC patients, 82 underwent TT plus bilateral central ND with/without lateral ND, while 73 underwent TT alone. The nodal metastasis pattern was determined and the recurrence, morbidity, and postoperative levels of serum calcium and PTH were compared between 2 groups. RESULTS: Of the 82 node dissection patients, metastatic nodes were present in the central neck of 51 (62.2%) and the lateral neck of 21 (25.6%) patients, most frequently in the ipsilateral and pretracheal central nodes and lateral jugular nodes. Four regional recurrences (2.6%) were found in 3 patients of the no node dissection group and one of the node dissection group (P = 0.37) during the follow-up lasting a mean 52 months. Overall morbidity and hypocalcemia was higher in the node dissection group than the no node dissection group (41 of 82, 50%; vs. 9 of 73, 12.3%; P < 0.001; 25 of 82, 30.5%; vs. 7 of 73, 9.6%; P = 0.001). Serum PTH levels significantly decreased immediately postoperatively in the node dissection group and remained low for several weeks thereafter. CONCLUSIONS: Serum PTH levels were significantly reduced following ND in PTC patients. Our data suggest that, when performing therapeutic ND plus TT, particular effort should be made to preserve the parathyroid glands and to monitor their function.     

Toxic effects of di(2-ethylhexyl)phthalate on mortality, growth, reproduction and stress-related gene expression in the soil nematode Caenorhabditis elegans

In this study, di(2-ethylhexyl)phthalate (DEHP) toxicities to Caenorhabditis elegans were investigated using multiple toxic endpoints, such as mortality, growth, reproduction and stress-related gene expression, focusing on the identification of chemical-induced gene expression as a sensitive biomarker for DEHP monitoring. The possible use of C. elegans as a sentinel organism in the monitoring of soil ecosystem health was also tested by conducting the experiment on the exposure of nematode to field soil. Twenty-four-hour median lethal concentration (LC50) data suggest that DEHP has a relatively high potential of acute toxicity to C. elegans. Decreases in body length and egg number per worm observed after 24h of DEHP exposure may induce long-term alteration in the growth and reproduction of the nematode population. Based on the result from the C. elegans genome array and indicated in the literatures, stress proteins, metallothionein, vitellogenin, xenobiotic metabolism enzymes, apoptosis-related proteins, and antioxidant enzyme genes were selected as stress-related genes and their expression in C. elegans by DEHP exposure was analyzed semi-quantitatively. Expression of heat shock protein (hsp)-16.1 and hsp-16.2 genes was decreased by DEHP exposure. Expression of cytochrome P450 (cyp) 35a2 and glutathione-S-transferease (gst)-4, phase I and phase II of xenobiotic metabolism enzymes, was increased by DEHP exposure in a concentration-dependent manner. An increase in stress-related gene expressions occurred concomitantly with the deterioration on the physiological level, which suggests an increase in expression of those genes may not be considered as a homeostatic response but as a toxicity that might have physiological consequences. The experiment with the soil from the landfill site suggests that the potential of the C. elegans biomarker identified in laboratory conditions should be calibrated and validated for its use in situ.     

The Clinical Outcome of Chemotherapy-Induced Amenorrhea in Premenopausal Young Patients with Breast Cancer with Long-Term Follow-up

Background

We investigated the factors that predict chemotherapy-induced amenorrhea (CIA) and the prognostic significance of CIA after long-term follow-up.

Methods

We reviewed data from 241 premenopausal patients with breast cancer who underwent adjuvant CMF or FAC chemotherapy after breast cancer surgery between January 1995 and December 2000.

Results

The median follow-up duration was 109.8 (range, 16.6–193.1) months. The age of CIA patients was older than non-CIA patients (median, 44 (range, 28–53) years and 36 (range, 25–49) years, respectively; P < 0.001). The addition of tamoxifen to the chemotherapy increased the incidence of CIA from 48% to 63.6% (P = 0.015). The 10-year disease-free survival (DFS) rate was higher in the CIA group compared with the non-CIA group in hormonal receptor-positive patients (78.4% vs. 67%, respectively; P = 0.022), and the 10-year overall survival (OS) rate also was higher in the CIA group compared with the non-CIA group (90.8% vs. 79.7%, respectively; P = 0.041).

Conclusions

The most important predictors of CIA are age and the addition of tamoxifen to the chemotherapy. CIA is likely to have an influence on DFS and OS in premenopausal patients with breast cancer with a positive hormone receptor, and it might be used as a surrogate marker for effective chemotherapy in these young Asian patients.     

Role of cortical dysplasia in epileptogenesis following prolonged febrile seizure

Purpose: Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model. Methods: Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM‐treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long‐term video‐EEG (electroencephalography). Results: The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC‐only and MAM‐only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group. Discussion: Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE.     

An association between RRM1 haplotype and gemcitabine-induced neutropenia in breast cancer patients

PURPOSE: We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity. PATIENTS AND METHODS: SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers. RESULTS: The incidences of SNPs of breast cancer patients were 1.4% in dCK (626 A>G), 10.8% in DCTD (315 T>C), 40.5% in the first RRM1 (1082 C>A), 44.6% in the second RRM1 (2455 A>G), 44.6% in the third RRM1 (2464 G>A), and 23% in two RRM1 sites (2455 A>G and 2464 G>A) that were similar to those of the normal control group. We found a double SNP of RRM1 (2455 A>G and 2464 G>A) to be the novel haplotype that was associated with a lower frequency of chemotherapy-induced toxicity, such as neutropenia (p < .01) and G-CSF requirement (p < .005). CONCLUSION: RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients.     

p38 mitogen-activated protein kinase contributes to angiotensin II-stimulated migration of rat aortic smooth muscle cells

In this study, we clarified the intracellular mechanism of angiotensin II (Ang II) in promoting migration in rat aortic smooth muscle cells (RASMCs). RASMC migration was measured with the Boyden chamber assay, and the result was confirmed with an aortic sprout assay. The activities of kinases were investigated by western blot analysis. Ang II enhanced RASMC migration, which was chemotaxis directed, and induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2), and heat shock protein 27 (Hsp27). Ang II-enhanced cell migration was inhibited by SB203580 (a p38 MAPK inhibitor) and piceatannol (a spleen tyrosine kinase inhibitor), but only partially by PD98059 (an ERK inhibitor) and PP2 (a Src inhibitor). The Ang II-stimulated phosphorylation of p38 MAPK and Hsp27 in RASMCs was inhibited by piceatannol and SB203580. The phosphorylation of ERK1/2 stimulated by Ang II was suppressed by PD98059, piceatannol, and PP2. Ang II increased the sprout outgrowth from aortic rings and this response was attenuated by pretreatment with SB203580, PD98059, PP2, or piceatannol. These results suggest that p38 MAPK contributes to the regulation of the Ang II-induced chemotactic migration of vascular smooth muscle cells, which is mediated by Hsp27 phosphorylation.     

Cervical sensory preservation during neck dissection

Although the practice of neck dissection has greatly advanced from radical to function-preserving surgery, the impact of the sensory nerve-preserving neck surgery on the pain and quality of life (QOL) of patients has received little study. We evaluated neck morbidity and its impact on QOL associated with selective or modified radical neck dissection with or without preservation of cervical root branches. We conducted a retrospective cohort study comparing 24 patients who had their cervical root branches preserved to 29 patients whose root branches were removed during neck dissection. The spinal accessory nerve was preserved and sex, age, pathologic status, side and extent of neck dissection, and radiotherapy were comparable between groups. The groups were compared based on sensory and motor functions of the neck and shoulder and questionnaires on depression and QOL at follow-up of mean 18.7 (range 12-34) months after surgery. The nerve-preserved patients showed a low incidence and severity of neck and shoulder pain compared to the nerve-removed subjects (p<.05). Loss of sensation was more frequently experienced in the nerve-removed group on the earlobe and the lateral neck of the operated side (p<.05). Depression and QOL scores were higher in the nerve-removed group and significantly correlated with pain intensity. Preservation of the cervical root branches reduces postoperative pain as well as permanent anesthetic areas of the neck. This may also improve the mental state and QOL of patients undergoing neck dissection.     

Curcumin Attenuates Radiation-Induced Inflammation and Fibrosis in Rat Lungs

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-κ B (NF-κB) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.