Assessment of Long-Term Hematologic Effects in Differentiated Thyroid Cancer Patients Treated with Radioactive Iodine

Objective: Radioactive iodine (RAI) therapy may cause hematologic abnormalities. The aim of this study is to evaluate long-term hematologic effects in differentiated thyroid cancer (DTC) patients after RAI therapy. Materials and Methods: A total of 1389 patients with DTC who were treated with RAI were retrospectively evaluated. Complete blood cell counts before RAI therapy and at last follow-up and hematologic malignancy development were obtained from the electronic records. Results: In the long-term analysis, thrombocytopenia and lymphopenia were observed significantly in patients over 60 years of age. Thrombocytopenia was observed more frequently in men. Leukopenia, thrombocytopenia, and lymphopenia were observed significantly with doses of >175 mCi. Thrombocytopenia and lymphopenia were observed significantly with multiple dose administration. Higher frequencies of anemia, thrombocytopenia, leukopenia, neutropenia, and lymphopenia were found in patients with advanced-stage disease. However, patients with advanced-stage disease had higher doses and more multiple doses than patients with early-stage disease. The rate of hematologic malignancy was found to be higher than in the general population. Conclusion: We suggest that cytopenia be surveyed more carefully in patients older than 60 years of age. The most important risk factor for lower platelets after RAI therapy is male gender. Clinically, the most important predictor for cytopenia is advanced disease stage, which is related to the combined effects of applied high dose activity, multiple dose applications, and high tumor burden.

Clinical, sonographical, and pathological findings of pediatric thyroid nodules.

Thyroid nodules are less frequent in children than in adults. A higher rate of malignancy is highlighted in this group. We aimed to analyze the clinical, laboratory, and ultrasound (US) findings of children and adolescents with benign and malignant thyroid nodules. This was a retrospective review of children and adolescents evaluated at a tertiary pediatric institution between 2007 and 2019. Patients with autonomously functioning nodules, autoimmune thyroid diseases, and a history of oncohematological disorders were excluded. A total of 102 patients with 131 nodules were identified. The study population included 57 females (55.9%); the average age was 10.6 ±4 years. Thirty-five nodules (26.7%) ranging 4.5-36 mm had a fine-needle aspiration (FNA) done: 45.7% (n = 16) were benign, 11.4% (n = 4) were classified as atypia, and 8.5% (n = 3) were consistent with papillary carcinoma. Fourteen patients (13.7%) underwent surgery. Five (4.9%) were finally diagnosed with papillary thyroid cancer. Of the 6 patients with benign FNAs, all except one, which was initially reported as atypia by an earlier FNA but was later diagnosed with papillary carcinoma, had a colloid nodular goiter. Of the 3 patients with atypia FNAs, one was found to be papillary carcinoma. One hundred twenty-five benign nodules (21 based on cytology and/or histology, 104 on clinical and imaging follow-up) were diagnosed. Nodule size, microcalcifications, solid parenchyma, and pathologic lymph node alterations were associated with malignancy, but nodule growth was not.Conclusion: Diagnostic approach and management of children with thyroid nodules should be based on a stepwise evaluation including clinical, laboratory, and US findings. Of the 102 patients identified, 4.9% had thyroid carcinoma below the range described in previous literature. What is Known: • Thyroid nodules are less frequent in children than in adults but more frequently malignant. Research on factors associated with malignancy have mostly been conducted in adults; further studies in pediatric thyroid nodules are warranted. What is New: • Microcalcifications, pathologic lymph node alterations, solid parenchyma, and larger nodule size are associated with malignant nodules, but nodule growth is not always suggestive of thyroid malignancy. The incidence of thyroid malignancy in this population was below the reported worldwide incidence in children with thyroid nodules.

Could pyelonephritic scarring be prevented by anti-inflammatory treatment? An experimental model of acute pyelonephritis.

OBJECTIVES: This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only. METHODS: Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, "ceftriaxone + ketoprofen," methylprednisolone, and "ceftriaxone + methylprednisolone" were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated. RESULTS: When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in "ceftriaxone + ketoprofen" group (P = 0.039). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in "ceftriaxone + methylprednisolone" group (P = 0.041). Renal scar score was declined in "ceftriaxone + ketoprofen" group and "ceftriaxone + methylprednisolone" group compared with no-treatment group on 10th week of the study (P = 0.026, P = 0.044). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in "ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone" (P = 0.011, P = 0.023). CONCLUSION: It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys.

A case of recurrent episodes of acute renal allograft failure caused by renal pedicle tortion.

BACKGROUND: Acute allograft failure which occur intermittently after renal transplantation caused by graft tortion is a very rare entity. We here report highly unusual case of recurrent episodes of acute allograft dysfunction two years after kidney transplantation secondary to ischemic tubular necrosis caused by tortion of renal pedicle due to rotation of the allograft with body movements. CASE PRESENTATION: A 55 year-old male patient with living unrelated kidney transplantation for chronic renal failure caused by autosomal dominant polycystic kidney disease had presented recurrent acute deteriorations in renal functions. All laboratory values were within normal limits except elevated serum creatinine levels, acute tubular necrosis in graft biopsy, and detection of pelvic dilatation in renal ultrasonography from time to time. Changes in axis of graft in nuclear medicine scans taken at different times during the same study made us bring to mind the diagnosis of renal pedicle tortion. Renal blood flow measurements with Doppler ultrasonography in different body positions helped to reach the final diagnosis of mobile kidney right on time. The patient is now well after prompt surgical treatment with nephropexy. DISCUSSION: Unfortunately, tortion of allograft once occurred is associated with very high rate of graft loss due to arterial compromise and infarction and it is very difficult to diagnose without high level of suspicion. We discuss the causes of renal allograft tortion and the measures to prevent its occurrence and the methods to diagnose.

A computer program for calculation of approximate embryo/fetus radiation dose in nuclear medicine applications.

OBJECTIVE: In this study, we aimed to make a computer program that calculates approximate radiation dose received by embryo/fetus in nuclear medicine applications. MATERIAL AND METHODS: Radiation dose values per MBq-1 received by embryo/fetus in nuclear medicine applications were gathered from literature for various stages of pregnancy. These values were embedded in the computer code, which was written in Fortran 90 program language. RESULTS: The computer program called nmfdose covers almost all radiopharmaceuticals used in nuclear medicine applications. Approximate radiation dose received by embryo/fetus can be calculated easily at a few steps using this computer program. CONCLUSION: Although there are some constraints on using the program for some special cases, nmfdose is useful and it provides practical solution for calculation of approximate dose to embryo/fetus in nuclear medicine applications. CONFLICT OF INTEREST: None declared.

Radiation dose to technologists per nuclear medicine examination and estimation of annual dose.

UNLABELLED: Conventional diagnostic nuclear medicine applications have been continuously increasing in most nuclear medicine departments in Turkey, but to our knowledge no one has studied the doses to technologists who perform nuclear medicine procedures. Most nuclear medicine laboratories do not have separate control rooms for technologists, who are quite close to the patient during data acquisition. Technologists must therefore stay behind lead shields while performing their task if they are to reduce the radiation dose received. The aim of this study was to determine external radiation doses to technologists during nuclear medicine procedures with and without a lead shield. Another aim was to investigate the occupational annual external radiation doses to Turkish technologists. METHODS: This study used a Geiger-Müller detector to measure dose rates to technologists at various distances from patients (0.25, 0.50, 1, and 2 m and behind a lead shield) and determined the average time spent by technologists at these distances. Deep-dose equivalents to technologists were obtained. The following conventional nuclear medicine procedures were considered: thyroid scintigraphy performed using (99m)Tc pertechnetate, whole-body bone scanning performed using (99m)Tc-methylene diphosphonate, myocardial perfusion scanning performed using (99m)Tc-methoxyisobutyl isonitrile, and (201)Tl (thallous chloride) and renal scanning performed using (99m)Tc-dimercaptosuccinic acid. RESULTS: The measured deep-dose equivalent to technologists per procedure was within the range of 0.13 ± 0.05 to 0.43 ± 0.17 µSv using a lead shield and 0.21 ± 0.07 to 1.01 ± 0.46 µSv without a lead shield. Also, the annual individual dose to a technologist performing only a particular scintigraphic procedure throughout a year was estimated. CONCLUSION: For a total of 95 clinical cases (71 patients), effective external radiation doses to technologists were found to be within the permissible levels. This study showed that a 2-mm lead shield markedly reduced the external dose to technologists. The doses to technologists varied significantly for different diagnostic applications. Consequently, the estimated annual dose to a technologist performing only a particular scintigraphic procedure is very different from one type of procedure to another. The results of this study should help in determining the rotation time of technologists in different procedures and differences in their individual techniques.

Treatment related changes in antifibrinolytic activity in patients with polycythemia vera.

Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by predominantly excessive erythrocyte production. During the course of the disease, bleeding or thrombosis may be observed. In PV patients, the influence of antifibrinolytic activities on development of thrombohemorrhagic complications remains to be elucidated. In the present study, alterations in antifibrinolytic activity of PV patients and the effects of treatments on these alterations were investigated. Newly diagnosed and therapy-naive 22 PV patients were included. Thrombomodulin (TM), plasmin-alpha 2-antiplasmin complex (PAP), plasminogen activator inhibitor-1 (PAI-1) and thrombin activable fibrinolysis inhibitor antigen (TAFIa) levels were measured in all individuals and after phlebotomy and 5-hydroxyurea (5-HU) therapy in PV patients. TM, PAP, PAI-1 and TAFIa values of the patient group were higher than those of the controls. After phlebotomy, no changes were detected in TM, PAI-1 and TAFIa values, but PAP values decreased. On the contrary, 5-HU treatment resulted in a marked decrease in TM, PAI-1, PAP and TAFIa levels. These findings suggested that the changes in antifibrinolytic activity and endothelial dysfunction might be contributed to formation of intravascular thrombosis in PV patients, even though not clinically overt. 5-HU in addition to phlebotomy affects antifibrinolytic activity and may have an influence on diminishing predisposition of thrombosis.

Optimal positioning in the detection of inferior wall infarct size with myocardial perfusion scintigraphy: prone vs. supine.

OBJECTIVE: The prone position is commonly utilized to reduce false positive perfusion defects because this position overcomes the diaphragmatic inferior wall attenuation in single-photon emission computerized tomography (SPECT) studies. We investigated whether the prone position had an important advantage over the supine position in determining the severity and extent of infarct in patients with acute inferior myocardial infarction (MI). METHODS: Twenty-nine male patients (mean age 61 ± 10 years) with acute inferior MI were enrolled in the cross-sectional study. After injection of thallium-201 (201Tl) under resting conditions, redistribution SPECT imaging was twicely performed in each subject, in both the supine and prone positions, consecutively. The extent and severity scores of the perfusion defects were calculated from the sum of individual segment scores. Myocardial infarction size was also evaluated using peak cardiac troponin T (cTnT) levels. Wilcoxon rank and Spearman's rank correlation tests were used for statistical analyses of data. RESULTS: For the supine vs. prone positions, the median defect severity scores were 8 (4-13) vs. 5 (0.5-8.5) and the defect extent scores were 4 (3-5.5) vs. 3 (0.5-4.5), respectively. Both perfusion defect scores in the prone position were significantly lower than those in the supine position (p=0.001). The mean peak cTnT level during hospitalization was 7.2 ± 3.9 µg/l. Peak cTnT levels were correlated with all SPECT parameters. However, the correlation was greater in the prone position (defect severity: r=0.712, p=0.001) (defect extent: r=0.790, p=0.001) than in the supine position (defect severity: r=0.495, p=0.01) (defect extent: r=0.481, p=0.01). CONCLUSION: In patients with inferior MI, the SPECT results revealed a significant difference between the supine and prone images. The perfusion extent and severity scores of SPECT in the inferior wall with prone imaging correlates better with the peak troponin compared to the supine position. Comparative studies that use advanced imaging tools are needed to verify our present findings.

The changes in complete blood count in thyroid cancer patients treated with radioactive iodine ablation therapy.

OBJECTIVE: The aim of this study was to evaluate the effect of radioactive iodine (RAI) ablation therapy on the complete blood count (CBC) in thyroid cancer patients. METHODS: One hundred sixty four patients undergoing RAI ablation therapy after total thyroidectomy were included. CBC results were available from the patients' medical records at the time of ablation and at the 1st, 6th, and 12th months after RAI therapy. RESULTS: Hemoglobin (Hb), white blood cell (WBC) and platelet (Plt) values were significantly lower than baseline at 1 month after treatment (p <0.0001). Hb and WBC values were increased at the 6th month and at the 1st year. Plt values increased at the 6th month but had decreased again at the 1st year. The values were usually in normal ranges except in the patients with low pretreatment Hb and WBC values. CONCLUSION: RAI ablation therapy in thyroid cancer patients is a safe treatment modality without any serious or persistent hematological side effects.

The effect of Hirudoid on random skin-flap survival in rats.

BACKGROUND: One of the main fields of research in flap surgery is to increase the viability of flaps. Many materials have been tested for this purpose. This study shows that topical application of Hirudoid, an organoheparinoid, increases flap survival of dorsal flaps in rats. METHODS: Hirudoid was used topically every day in eight of 16 rats in which 10x3-cm dorsal flaps were prepared. The flaps were taken for analysis on the 10th day. Analysis of the flaps was performed using digital measurement and scintigraphy. RESULTS: Analysis revealed that the flap necrosis area was smaller in the Hirudoid group compared to the control group. In addition, the area exhibiting radioactive uptake in scintigraphy was greater in the treatment group. CONCLUSION: Topical administration of Hirudoid may significantly improve flap survival.

Relationship between serum neutrophil count and infarct size in patients with acute myocardial infarction.

PURPOSE: We investigated the relationship between scintigraphic infarct size and neutrophil counts after acute myocardial infarction (AMI), which has not been adequately studied with imaging tools. METHODS: Twenty-eight consecutive patients with anterior AMI were included in the study. Total white blood cell (WBC), neutrophil counts, creatine kinase-myocardial band (CKMB), and cardiac troponin (cTnT) were obtained at admission and daily during the first 72 h after a patient's arrival. Single photon emission computed tomography studies were performed at a median interval of 4 days (range, 3-5 days) after the AMI. The severity scores of perfusion defects were calculated. WBC and neutrophil counts correlated with enzymatic and single photon emission computed tomography infarct size. RESULTS: Leukocyte and neutrophil counts on admission and first day were positively correlated with peak CKMB, peak cTnT, and scintigraphic infarct size. There were no statistical correlations on the second and third days (P>0.05). The most significant relationship was between basal neutrophil counts and scintigraphic infarct size (r = 0.602, P<0.001). Overall, the correlation coefficients with scintigraphy were better than those with peak CKMB and cTnT levels for both WBC and neutrophil counts. CONCLUSION: Measuring basal neutrophil counts may be considered as an alternative solution in the prediction of infarct size.

Effects of human amniotic fluid on fracture healing in rat tibia.

BACKGROUND: Human amniotic fluid (HAF), including hyaluronic acid (HA) and several growth factors, has been used experimentally in tendon, nerve, and cartilage regeneration and in bone defects because of its positive stimulating effects on regeneration potential. This study was performed to investigate whether HAF was effective on fracture healing. MATERIALS AND METHODS: We created 36 tibial fractures in 20-week-old Wistar rats that were divided into three groups. In group 1, fracture lines were instilled with HAF collected at 18th week of the gestation and, in group 2, fracture lines were instilled with HAF obtained at the end of the gestation. HAF which was collected from different period of gestation was used, because the concentration of HA and growth factors in HAF varies considerably during gestation. Group 3 was used as an operative control group. RESULTS: Fracture-healing score was highest in group 1 radiologically at the 3rd and 5th week (P = 0.037, P = 0.018, respectively). In the scintigraphic evaluation, metabolic activity at the fracture site was observed in group 1 more than the others at the 3rd week (P = 0.010). Histologically, the highest scores were obtained from group 1 as compared to other groups at the 3rd and 5th week. In the 5th week, predominant cartilage with some woven bone was observed in group 3, while predominantly woven bone with some cartilage was observed in group 1 (P = 0.036). CONCLUSIONS: Our data suggest that HAF had a positive effect on fracture healing in rat tibia, and also this positive effect was observed more in group 1.

The association of bladder myeloid sarcoma and unclassified myelodysplastic/myeloproliferative disease.

Myeloid sarcoma of urinary bladder is a rare disorder. We report a 71-year old man with hematuria. He was also under follow up for unclassified myeloproliferative/ myelodysplastic disorder, diagnosed 2 months ago. Abdominal ultrasonography and computed tomography findings were normal. Diagnostic cystoscopy revealed patchy areas of mucosal swelling with hyperemia. Histopathological examination of biopsies demonstrated a neoplasm composed of blasts showing myeloperoxidease positivity by immunohistochemistry. To our knowledge, current case is the first case of myeloid sarcoma without evidence of a mass lesion in the urinary bladder with a concurrent diagnosis of myelodysplastic /myeloproliferative disease, unclassifiable.

Effect of pathologic fractures on survival in multiple myeloma patients: a case control study.

BACKGROUND: Multiple Myeloma (MM) is a B cell neoplasm characterized by the clonal proliferation of plasma cells. Skeletal complications are found in up to 80% of myeloma patients at presentation and are major cause of morbidity. METHODS: 49 patients were enrolled with MM admitted to Black Sea Technical University Hospital between 2002-2005. Pathologic fractures (PFs) were determined and the patients with or without PF were followed up minimum 3 years for survival analysis. RESULTS: PF was observed in 24 patients (49%) and not observed in 25 patients (51%). The risk of death was increased in the patients with PF compared with patients who had no fractures. While overall survival was 17.6 months in the patients with PFs, it was 57.3 months in the patients with no PFs. CONCLUSION: These findings suggest that PFs may induce reduced survival and increased mortality in the MM patients, however, larger sample size is essential to draw clearer conclusions added to these data.

An unusual etiology of erythropoietin resistance: hyperthyroidism.

Many possible causes of resistance to human recombinant erythropoietin (rh-EPO) have been reported in patients with renal failure. This case presents an unusual cause of erythropoietin-resistant anemia in a patient with chronic renal failure. A 61-year-old male patient who was on chronic hemodialysis program due to diabetic nephropathy for seven months developed erythropoietin resistant anemia. No iron deficiency was revealed by laboratory data, no megaloblastic anemia were found by biochemical investigation, and no inflammatory states including infection or neoplastic diseases were disclosed by abdominal ultrasonography, chest X-ray, bone marrow aspiration and biopsy, or other methods (normal C-reactive protein levels). This hemodialysis patient had epoetin-resistant anemia with primary autoimmune hyperthyroidism. The anti-thyroid therapy was effective not only against the hyperthyroidism but also against his epoetin resistant anemia.

The role of hepatocyte growth factor in the differentiation of dendritic cells from peripheral blood monocytes.

OBJECTIVE: To find out the effects of hepatocyte growth factor (HGF) in the development of dendritic cells (DC) from the peripheral monocytes. METHODS: The study was carried out in Black Sea Technical University Hospital, Trabzon, Turkey between 2003-2004. Seven different cytokine combinations were employed to assess phenotypical and functional differences of DCs from the peripheral monocytes in serum free culture media. Peripheral monocytes were incubated in media with cytokines for 5 days. The tumor necrosis factor-alpha (TNF-alpha) was added to the cell culture on day 5 and incubated for another 2 days. Surface and co-stimulating molecules on the cells were assessed by flowcytometry. The functional capacity of the DCs was evaluated on day 7 by purified protein derivative loading and subsequent lymphoproliferation test using methyl tetrazolium staining. RESULTS: On the 5th day of incubation DC development was observed in all cytokine groups, but cells were superior in cultures maintained in the presence of interleukin-4 combinations with granulocyte-macrophage colony stimulating factor (GM-CSF) or with GM-CSF+HGF. Moreover, the expression of surface and co-stimulating molecules increased significantly after incubation with TNF-alpha. The effect of PPD loaded-DCs on proliferation of lymphocytes was more striking in HGF containing groups. CONCLUSION: It was concluded that HGF supplemented cultures exert some additive effects in relation to function of monocyte-derived DCs. But HGF alone does not seem to augment monocyte-derived DC proliferation and maturation significantly.

Effects of interferon-alpha-2a on Th3 cytokine response in multiple myeloma patients.

AIMS AND BACKGROUND: Multiple myeloma cells increase Th3 cytokine response by secreting TGF-beta, which causes defective Th1 and Th2 cytokine responses. Therefore, a significant suppression of the immune system is seen in multiple myeloma. Interferon-alpha (IFN-alpha) is used in the treatment of multiple myeloma due to its immunomodulatory and anti-tumoral effects. We attempted to define the characteristics of immune cytokine responses and the effects of IFN-alpha-2a on the immune response in multiple myeloma. METHODS: Fifteen patients with multiple myeloma and 15 healthy controls were enrolled. IFN-alpha-2a, 3 million units/day x 3 times/week, was administered subcutaneously to the patients for 2 weeks. Cytokines (TGF-beta, IL-1, IL-2, IL-4, IL-10, IFN-gamma) were assessed by the ELISA method in sera of the patients in pretreatment and posttreatment periods and in the sera of the controls. RESULTS: IL-2 and IL-4 levels in patients, before IFN-alpha-2a, were lower than the controls, whereas TGF-beta levels were higher than the controls. In other words, Th3 cytokine response was increased and Th1 and Th2 cytokine responses were decreased in patients. A short course of IFN-alpha-2a increased IL-2 levels. CONCLUSIONS: These findings suggest IFN-alpha-2a may enhance nonTh3 cytokine responses in multiple myeloma patients.