Predictive role of nontumoral sodium iodide symporter activity and preoperative thyroid characteristics in remission process of thyroid cancer patients

Objective

The target of radioiodine ablation therapy (RIAT) after complete tumor removal is the nontumoral remnant tissue. We aimed to evaluate sodium iodide symporter (NIS) expression in nontumoral thyroid tissue in differentiated thyroid cancer (DTC) patients who have complete but delayed structural response (DSR) to RIAT after surgery. Preoperative thyroid characteristics such as volume and nontumoral histology were also investigated for both DSR and its control group as potential predictors of insufficient NIS activity in this study.

Methods

Total of 600 patients with postoperative remnant thyroid tissue and who were in remission after RIAT spontaneously, were included in the study. Patients with positive diagnostic whole body scan (DxWBS) with thyroid bed uptake and stimulated serum Tg level <2 ng/mL at first year visit after initial therapy were defined as DSR group. Immunohistochemical staining of NIS protein was performed on the nontumoral tissue sections from surgery and semi quantified in terms of density and intensity. DSR and its control group were also compared in terms of NIS expression, radioiodine (RAI) uptake on post-therapy scan and preoperative thyroid characteristics.

Results

When compared with the control group, the density and intensity of NIS expression as well as the intensity of RAI uptake were significantly lower in DSR group (p = 0.001). There were also significant differences between groups regarding preoperative thyroid characteristics; i.e. preoperative thyroid volumes were significantly higher and the presence of concurrent benign thyroid disease was significantly more common in DSR group (p = 0.035, p = 0.001). Hashimoto thyroiditis was 8.59 times higher (95 % CI; 2.31–31.96) and multinodular goiter was 7.50 times higher (95 % CI; 1.88–29.91) among DSR group when compared with the control group.

Conclusions

Our findings suggest that insufficient NIS activity in nontumoral thyroid tissue associates with DSR in DTC patients who have postoperative remnant tissue. Preoperative thyroid characteristics such as volume and concomitant benign thyroid disease may have an important role in predicting the complete response time to RIAT in these patients.     

Prediction of pituitary down-regulation by evaluation of endometrial thickness in an IVF programme

The aim of this retrospective study was to determine whether pituitary down-regulation after gonadotrophin-releasing hormone analogue (GnRHa) administration can be accurately predicted by transvaginal ultrasonographic measurement of endometrial thickness in the presence of menstruation. All cycles of an IVF/intracytoplasmic sperm injection programme in which a long protocol of GnRHa was used for ovarian stimulation were analysed. Overall, 209 patients underwent 223 treatment cycles. Using a serum oestradiol concentration of 50 pg/ml as a cut-off point, the sensitivity, specificity, predictive value and false positive and false negative values were calculated for prediction of pituitary down-regulation from endometrial thickness measurements. Pituitary down-regulation was achieved in 223 treatment cycles in 180 patients (80%). The best combination of the highest specificity (71.7%) and sensitivity (62.5%) is achieved with a linear appearance of the endometrium. Therefore, ultrasonographic measurement of endometrial thickness should be used in combination with serum oestradiol concentration in estimating pituitary down-regulation after GnRHa. In conclusion, the linear appearance of endometrium can be as reliable as serum oestradiol concentration in prediction of pituitary down-regulation after GnRHa.     

Design and <Emphasis Type="BoldItalic">In Vitro</Emphasis> Evaluation of Bispecific Complexes and Drug Conjugates of Anticancer Peptide,LyP-1 in Human Breast Cancer

Purpose

LyP-1, a nine-amino-acid tumor homing peptide, selectively binds to its cognate receptor, p32. Overexpression of p32 in certain tumors should allow use of LyP-1 as a targeting agent for the delivery of therapeutic or diagnostic agents. Peptide conjugates are developed for enhanced pre-targeting of MDA-MB-231 breast cancer cells with peptide-antibody bispecific complexes and targeting with multiple-drug/-fluorophore-conjugated nano-polymers.

Methods

LyP-1-anti-DTPA bispecific antibody complexes (LyP-1-bsAbCx) were generated by conjugation of anti-DTPA antibody and LyP-1. LyP-1–doxorubicin (Dox), Dox-DTPA-succinyl-polylysine (Dox-DSPL), Dox-DSPL-LyP-1, DTPA-Dox-poly glutamic acid (D-Dox-PGA) or DTPA-rhodamine conjugated polylysine (DSPL-RITC) were prepared. In vitro therapeutic efficacy and targeting by immunofluorescence in MDA-MB-231 breast cancer cells were assessed with Dox-LyP-1. Immunofluorescence visualization of cancer cells was evaluated after pretargeting with LyP-1-bsAbCx and targeting with DSPL-RITC.

Results

Cytotoxicity of Dox-LyP-1 conjugates was significantly greater than free doxorubicin (p?<?0.0001). For fluorescent-labeled LyP-1, internalization occurred in 30 min in tumor cells. Fluorescence intensity of two-step targeted cells showed that pretargeting with LyP-1-bsAbC, followed by targeting with DSPL-RITC was greater than non-pretargeted DSPL-RITC (p?<?0.05).

Conclusions

Peptide-conjugates are effective targeting agents for MDA-MB-231 breast cancer cells in culture. LyP-1-bsAbCx and Dox-LyP-1 conjugates may allow development of novel targeted cancer therapy and diagnosis.

     

Urinary Neopterin Levels in Patients with Thyroid Cancer

Increased urinary neopterin concentrations have been described in many cancers. We aimed to evaluate the urinary neopterin levels in thyroid cancer. Sixty-nine patients with thyroid cancer, 76 patients with benign thyroid pathology and 33 healthy subjects were evaluated. First morning urine samples were collected from the patients and normal subjects for neopterin and creatinine measurement and stored at −80 °C until analysed. Neopterin levels were 149.3 (15.2–1,602.2) μmol/mol creatinine in the malignant group, 32 (5.2–275.6) μmol/mol creatinine in the benign group and 9.2 (2.7–78.7) μmol/mol creatinine in normal subjects (p ≤ 0.001). Urinary neopterin levels were significantly higher in patients with thyroid cancer than patients with benign thyroid pathologies and normal subjects. Also the patients with benign thyroid pathologies had a higher urinary neopterin level than the normal subjects. Malignant group was divided to two groups; patients with/without chronic thyroiditis (confirmed histologically). There were 22 (31.9 %) patients with and 47 (68.1 %) patients without chronic thyroiditis. Urinary levels of neopterin didn’t differ in both groups (168.6 (21.3–716.8) μmol/mol creatinine and 135.3 (15.2–1,602.2) μmol/mol creatinine respectively; p = 0.381). Urinary neopterin levels are high in thyroid cancer patients independently from the presence of chronic thyroiditis.     

Comparison of serological and clinical findings in Turkish patients with cystic echinococcosis

Summary Cystic echinococcosis (CE), caused by the cestode Echinococcus granulosus, is potentially dangerous for humans. The aim of this study was to examine serological and clinical findings regarding cysts localisation and individual responses in 54 patients with CE. The majority of patients in this study were females (63 %) and the average age was 46.3 years. Most of the patients lived in rural areas or kept a dog (46 %) for a long time. The most frequent symptoms were hypochondrial pain (48.9 %), epigastrial discomfort (27.7 %), vomiting (21.3 %), minor cough (12.8 %), urticaria (6.3 %), weakness (4.3 %), fever (2.1 %), side-or back-ache (4.3 %). However, 17 % of the patients showed no symptoms. In every case, the ultrasound (USG) and/or computer tomography (CT) investigations were positive. In most cases (53.2 % of the patients) a single cyst was found but 46.8 % of the patients had multiple cyst formations (from 2 to 9 cysts) located in the liver. Sporadic lung, splenetic, mesenterial, tibial and cerebral localisations were also found. The patients were individually treated with albendazol (10–15 mg/kg) five days prior and six months after the surgical treatment. Serum samples were investigated by the serological techniques: IHAT, ELISA and Western blot using hydatid fluid antigen. In the patient sera, the specific antibody levels were mostly increased after surgery. Different results were obtained only in two patients. In the first case, seroconversion was delayed. In the other case all ELISA results were negative, however, the Western blot analysis and surgery proved the presence of CE. The results suggest that the different antibody response of patients depends on the individual immune response. Multiple localization and various stages of CE cysts demonstrate the necessity of a complex approach for the confirmation of a correct diagnosis.     

Factors playing a role in the development of decreased bone mineral density in juvenile chronic arthritis

OBJECTIVE: The aims of this study were to evaluate bone mineral density (BMD) in patients with juvenile chronic arthritis (JCA), compare them with healthy controls, and assess the effects of disease activity and corticosteroid treatment on BMD. METHODS: Twenty-eight patients diagnosed with JCA and 45 healthy controls were included in this study. Disease activity was determined by clinical and laboratory evaluation, Articular Disease Severity Score (ADSS), and the Juvenile Arthritis Functional Assessment Report (JAFAR). Bone mineral density of the lumbar spine was measured by dual energy X-ray absorptiometry (DEXA). RESULTS: Patients with JCA showed significant decreases in BMD compared with healthy controls. The JCA patients treated with corticosteroids showed significantly lower BMDs than the healthy control group. Age of the patients and age of onset were found to correlate with BMD. CONCLUSION: Our study showed that glucocorticoids were involved in the development of osteoporosis in JCA, with many other factors affecting bone mineralization. We could not demonstrate any relationship between BMD and disease activity, but the study data suggest that early onset disease is also an important factor in the development of osteoporosis in JCA.     

Performance of Venous Port Catheter Insertion by a General Surgeon: A Prospective Study

As part of the vascular access procedures, venous ports, commonly referred to as catheters, are placed under the skin to enable safe and easy vascular access for administration of repeated drug treatments. 122 patients who had received a venous port catheter insertion procedure in the general surgery department between January 1012 and January 2014 were involved in this study. Patients were divided into two groups: those who had undergone a fluoroscopy (group 1) and those who had not undergone a fluoroscopy (group 2). Complications that emerged during and after the port catheter insertion procedure and successful insertion rates were recorded in the database. Data of these patients were presented in a prospective manner. There were 92 to 30 patients in groups 1 and 2, respectively. In group 1, the mean age was approximately 56.8, total catheter stay time was 20,631 days, and mean time of port use was 224.2 days. In group 2, the mean age was approximately 61.2, total catheter stay time was 13,575 days, and mean time of port use was 452.5 days. Successful insertion rate was 100% and 90% in groups 1 and 2, respectively (P < 0.05). The proper insertion of the port catheter accompanied by monitoring methods can decrease procedure-related complications. Statistical comparisons between the two groups in terms of malposition and successful insertion rates also support this view (P < 0.05). The findings support the view that in cancer patients, a venous port catheter insertion accompanied by a fluoroscopy can be safely performed by general surgeons.Key words: Cancer, Infusion treatment, Port catheterCentral venous access is used in long-term intravenous chemotherapy, antibiotics infusion, parenteral nutrition, and transfusion of blood products.¹ Subcutaneous-inserted venous port catheters (VPC) are preferred over peripheral catheters in that they are more comfortable for the patient and have reduced wound infection rates, especially in patients that receive intermittent and long-term infusion treatment.² Since it was first defined by Morris et al³ in 1992, the use of venous port implantation has been increasingly widespread. Its advantages include ease of insertion under local anesthesia, minimal discomfort to the patient, low rates of complication, and the ability to continue treatment at home after patient has been discharged.⁴ The most common port complications are infection, malposition, catheter occlusion, catheter breakage, and failure of blood return from the catheter.^5,6 In the literature,^7,8 VPC insertion procedures are performed by oncologists, radiologists, and surgeons. The performance of a fluoroscopy and an ultrasonography is recommended for the prevention of dislocation, subclavian arterial thrombosis, and pneumothorax.^9,10 In this study, we aimed to identify the importance of the use of a fluoroscopy in the VPC insertion procedure and to demonstrate that general surgeons can perform this procedure as successfully as radiologists.