Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.
Bone Density Conservation Agents/therapeutic use* ; Bone Neoplasms/secondary* ; Denosumab/therapeutic use* ; Diphosphonates/therapeutic use* ; Endothelins/antagonists & inhibitors* ; Humans ; Male ; Prostatic Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Radioisotopes/therapeutic use* ; Radiopharmaceuticals/therapeutic use* ; Radium/therapeutic use* ; Samarium/therapeutic use* ; Strontium Radioisotopes/therapeutic use*

We evaluated the efficacy of recombinant human thyroid-stimulating hormone (rhTSH) versus thyroid hormone withdrawal (THW) prior to radioiodine remnant ablation (RRA) in thyroid cancer. A systematic search of MEDLINE, EMBASE, the Cochrane Library, and SCOPUS was performed. Randomized controlled trials that compared ablation success between rhTSH and THW at 6 to 12 months following RRA were included in this study. Six trials with a total of 1,660 patients were included. When ablation success was defined as a thyroglobulin (Tg) cutoff of 1 ng/mL (risk ratio, 0.99; 95% confidence interval, 0.96-1.03) or a Tg cutoff of 1 ng/mL plus imaging modality (RR 0.97; 0.90-1.05), the results of rhTSH and THW were similar. There were no significant differences when ablation success was defined as a Tg cutoff of 2 ng/mL (RR 1.03; 0.95-1.11) or a Tg cutoff of 2 ng/mL plus imaging modality (RR 1.02; 0.95-1.09). When a negative 131I-whole body scan was used solely as the definition of ablation success, the effects of rhTSH and THW were not significantly different (RR 0.97; 0.93-1.02). Therefore, ablation success rates are comparable when RRA is prepared by either rhTSH or THW.
Catheter Ablation ; Clinical Trials as Topic ; Databases, Factual ; Humans ; Iodine Radioisotopes/*therapeutic use ; Radiopharmaceuticals/*therapeutic use ; Recombinant Proteins/biosynthesis/genetics/therapeutic use ; Risk ; Thyroglobulin/analysis/metabolism ; Thyroid Neoplasms/*drug therapy/ultrasonography ; Thyrotropin/genetics/metabolism/*therapeutic use ; Treatment Outcome ; Whole Body Imaging

OBJECTIVE: To evaluate the usefulness of a beta-emitting radionuclide (holmium-166-chitosan complex) as a sclerosing agent for the treatment of renal cysts. MATERIALS AND METHODS: Using 10-30 mCi of holmium-166-chitosan complex, 20 renal cysts in 17 patients (14 male and 3 female patients, ranging in age from 47 to 82 years) were treated by percutaneous sclerotherapy under ultrasonographic guidance. The volume of the cysts before and after the sclerotherapy and the percentage change in volume were calculated in order to evaluate the response to therapy, which was classified as either complete regression (invisible), nearly complete regression (< 15 volume% of initial volume), partial regression (15-50 volume%) or no regression (> 50 volume%). RESULTS: The follow-up period ranged from 6 to 36 months (mean 28 months). Eighteen cysts (90%) regressed completely (n=11, 55%) or near-completely (n=7, 35%). Partial regression was obtained in one patient (5%) and there was no regression in one patient (5%). No significant complications were encountered. CONCLUSION: The holmium-166-chitosan complex seems to be useful as a new painless sclerosing agent for the treatment of renal cysts with no significant complications.
Aged ; Aged, 80 and over ; Chitin/*analogs & derivatives/*therapeutic use ; Female ; Holmium/*therapeutic use ; Human ; Kidney, Cystic/*radiotherapy ; Male ; Middle Aged ; Organometallic Compounds/*therapeutic use ; Radiopharmaceuticals/*therapeutic use ; *Sclerotherapy ; Support, Non-U.S. Gov't

Thyrotoxic periodic paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. All ethnicities can be affected, but TPP typically presents in men of Asian descent. The most common cause of TPP in thyrotoxicosis is Graves' disease. However, TPP can occur with any form of thyrotoxicosis. Up to our knowledge, very few cases ever reported the relationship between TPP and painless thyroiditis. We herein report a 25-yr-old Korean man who suffered from flaccid paralysis of the lower extremities and numbness of hands. The patient was subsequently diagnosed as having TPP associated with transient thyrotoxicosis due to painless thyroiditis. The paralytic attack did not recur after improving the thyroid function. Therefore, it is necessary that early diagnosis of TPP due to transient thyrotoxicosis is made to administer definite treatment and prevent recurrent paralysis.
Administration, Oral ; Adult ; Anti-Arrhythmia Agents/therapeutic use ; Humans ; Hypokalemic Periodic Paralysis/*diagnosis/drug therapy/etiology ; Male ; Organotechnetium Compounds/chemistry/diagnostic use ; Potassium Chloride/therapeutic use ; Propranolol/therapeutic use ; Radiopharmaceuticals/diagnostic use ; Thyroiditis/*complications/radiography/ultrasonography ; Thyrotoxicosis/*diagnosis/etiology

Azathioprine is frequently used for the treatment of inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. Lymphomas, squamous cell carcinomas, and undifferentiated pleomorphic sarcomas have been reported among patients receiving azathioprine therapy. Herein, we report a case of pleomorphic liposarcoma of chest wall which occurred in a 44-year-old man with Crohn's disease taking azathioprine. He was diagnosed with Crohn's disease 3 years ago after suffering from abdominal pain and hematochezia for 12 years. He had been taking 50 mg of azathioprine per day for 23 months when he visited the thoracic and cardiovascular surgery clinic due to right chest palpable mass that had rapidly grown during the past 2 months. Excisional biopsy was performed and the mass was diagnosed as pleomorphic liposarcoma. Therefore, he underwent radical excision of the right chest wall mass, which measured 11.0x6.5 cm in size. He is scheduled to receive radiation therapy and chemotherapy.
Adult ; Azathioprine/*therapeutic use ; Colonoscopy ; Combined Modality Therapy ; Crohn Disease/complications/*drug therapy ; Fluorodeoxyglucose F18/diagnostic use ; Humans ; Immunosuppressive Agents/*therapeutic use ; Liposarcoma/complications/*pathology/surgery ; Male ; Positron-Emission Tomography ; Radiopharmaceuticals/diagnostic use ; Tomography, X-Ray Computed

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The only curative treatment modalities for HCC are surgery, percutaneous ablation, and liver transplantation. Unfortunately, the majority of patients have unresectable disease at diagnosis. Therefore, effective treatment options are needed for patients with advanced HCC. The current standard treatment for patients with advanced HCC, according to the Barcelona Clinic Liver Cancer staging system, is the multikinase inhibitor sorafenib. Other alternative therapies are required, due to the limited treatment response to, and tolerance of, this molecular target agent. Clinical trials of hepatic artery infusion chemotherapy, radioembolization, and multimodal treatments have shown favorable results in advanced HCC patients. This article introduces new treatment modalities for advanced HCC and discusses future therapeutic possibilities.
Antineoplastic Agents/administration & dosage/*therapeutic use ; Carcinoma, Hepatocellular/enzymology/pathology/*therapy ; Combined Modality Therapy ; Embolization, Therapeutic/*methods ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Liver Neoplasms/enzymology/pathology/*therapy ; Molecular Targeted Therapy ; Niacinamide/analogs & derivatives/therapeutic use ; Phenylurea Compounds/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Radiopharmaceuticals/therapeutic use ; Signal Transduction/drug effects ; Treatment Outcome

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a matter that still remains to be resolved. Herein, the inhibitory effect of locally delivered (99m) Tc-HMPAO (hexamethyl propylene amine oxime) on neointimal hyperplasia after coronary stenting was examined in a pocine model, and its safety and efficacy observed in patients with coronary stent restenosis. METHODS: After a stent overdilation injury, local radioisotope delivery using (99m) Tc-HMPAO was applied to one coronary artery (Group I) and control therapy to another (Group II) in each of 10 pigs. Follow-up coronary angiogram (CAG) and histopathologic assessment were performed 4 weeks after stenting. Eleven patients (10 males and one female, 62.4 +/- 5.7 years of age) underwent local administration of 30 mCi/ 2 mL (99m) Tc-HMPAO shortly after PCI, via a Dispatch CatheterTM, followed by a whole body scan to evaluate the distribution of the (99m) Tc-HMPAO, as well as a thallium-201 (Tl-201) myocardial scan to evaluate myocardial perfusion. The major adverse cardiac events (MACE) were assessed during a one-year clinical follow-up. RESULTS: On histopathological analysis, the neointimal areas were 1.2 +/- 0.6 and 2.7 +/- 0.4 mm2 (p=0.002), and the histopathological areas of stenosis were 27.16.3 and 53.4 +/- 5.2% in Groups I and II (p=0.001), respectively. In the clinical study, there was no in-hospital MACE. On a quantitative coronary angiographic analysis, the minimal luminal diameter was increased from 0.4 +/- 0.3 to 2.9 +/- 0.2 mm, and diameter stenosis decreased from 84.2 +/- 9.5 to 16.3 +/- 11.0% following PCI. Follow-up CAG was performed in 9 cases (81.8%) and restenosis occurred in 2 (22.2%). On a follow-up CAG, the minimal luminal diameter, diameter stenosis rate, lumen loss and loss index were 2.0 +/- 0.8 mm, 27.7 +/- 2.9%, 0.7 +/- 0.7 mm and 0.2 +/- 0.3, respectively. During the one-year clinical follow-up there were no cases of death or acute MI, but two cases of target vessel revascularization (18.2%). CONCLUSION: Local delivery of (99m) Tc-HMPAO, a novel radiotherapy, can be used safely and effectively for coronary stent restenosis.
Angioplasty, Transluminal, Percutaneous Coronary ; Animals ; Brachytherapy/*methods ; Coronary Angiography ; Coronary Restenosis/*radiotherapy ; Female ; Humans ; Male ; Middle Aged ; Radiopharmaceuticals/*therapeutic use ; Research Support, Non-U.S. Gov't ; *Stents ; Swine ; Technetium Tc 99m Exametazime/*therapeutic use

OBJECTIVE: To assess actual rates of late vaginal stenosis and identify predisposing factors for complications among patients with previously untreated cervical cancer following high-dose-rate brachytherapy. METHODS: We performed longitudinal analyses of 57 patients using the modified Dische score at 6, 12, 18, 24, 36, and 60 months after treatment, which consisted of 15 interstitial brachytherapys and 42 conventional intracavitary brachytherapys, with a median follow-up time of 36 months (range, 6 to 144 months). RESULTS: More than half of the patients developed grade 1 (mild) vaginal stenosis within the first year of follow-up, and grade 2 (97.5%, moderate) to grade 3 (severe) stenosis gradually increased with time. Actual stenosis rates for grade 1, 2, and 3 were 97.5% (95% confidence interval [CI], 92.7 to 97.5), 60.7% (95% CI, 42.2 to 79.3), and 7.4% (95% CI, 0 to 18.4) at 3 years after treatment. Pallor reaction grade 2-3 at 6 months was only a statistically significant predisposing factor for grade 2-3 late vaginal stenosis 3 years or later with a hazard ratio of 3.48 (95% CI, 1.32 to 9.19; p=0.018) by a multivariate Cox proportional hazard model. Patients with grade 0-1 pallor reaction at 6 months showed a grade > or =2 vaginal stenosis rate of 53%, whereas the grade 2-3 pallor reaction group achieved a grade > or =2 vaginal stenosis rate at 3 years at 100% (p=0.001). CONCLUSION: High-dose-rate brachytherapy was associated with high incidence of late vaginal stenosis. Pallor reaction grade 2-3 at 6 months was predictive of late grade 2-3 vaginal stenosis at 3 years after treatment. These findings should prove helpful for patient counseling and preventive intervention.
Adult ; Aged ; Aged, 80 and over ; Brachytherapy/*adverse effects/methods ; Constriction, Pathologic/etiology/pathology ; Female ; Humans ; Iridium Radioisotopes/therapeutic use ; Middle Aged ; *Pallor ; Prognosis ; Prospective Studies ; Radiopharmaceuticals/therapeutic use ; Retrospective Studies ; Uterine Cervical Neoplasms/*radiotherapy ; Vaginal Diseases/*etiology/pathology

Percutaneous approaches, such as percutaneous ethanol injection and radiofrequency ablation, have been most widely used for hepatocellular carcinoma patients who were not eligible for surgery. New technologies to improve the efficacy are currently needed. 166Holmium is a neutron activated radionuclide, and has several beneficial radiophysical characteristics for internal radiation therapy. 166Holmium-Chitosan complex, in which chitosan is chelated with 166Holmium, was developed as a radiopharmaceutical for cancer therapy. We have conducted a pilot study to evaluate the clinical efficacy of transarterial administration of 166Holmium-Chitosan complex in patients with a single and small (< 3 cm) hepatocellular carcinoma. 166Holmium-Chitosan complex, at a dose of 20 mCi per cm of tumor mass-diameter, was administered through the artery that directly fed the tumor. Twelve patients were treated with a median follow-up duration of 26 (range: 12-61) months. The tumor diameter ranged between 1.5 and 2.5 cm. Ten patients (83%) had complete response and two (17%) had partial response. The median complete response duration was not reached. The median AFP level declined from 83.8 to 8.3 ng/mL within 2 months after treatment. No grade III/IV toxicity was observed. Grade I and II toxicities were observed in four patients (2 abdominal pain, 1 fever, and 1 AST/ALT elevation). No toxic death occurred. This preliminary study shows a promising and durable complete response rate with an acceptable safety profile. Further studies with greater accrual of patients are warranted.
alpha-Fetoproteins/metabolism ; Tomography, X-Ray Computed ; Radiopharmaceuticals/administration & dosage/*therapeutic use ; Pilot Projects ; Middle Aged ; Male ; Liver Neoplasms/pathology/radiography/*radiotherapy ; Injections, Intra-Arterial ; Humans ; Female ; Chitosan/administration & dosage/*therapeutic use ; Carcinoma, Hepatocellular/pathology/radiography/*radiotherapy ; Aged ; Adult

OBJECTIVE: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism. MATERIALS AND METHODS: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program. RESULTS: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls. CONCLUSION: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.
Adrenergic beta-Antagonists/*pharmacology/therapeutic use ; Aged ; Brain/*drug effects/metabolism/radiography ; Brain Mapping ; Essential Tremor/*diagnosis/drug therapy/radiography ; Fluorodeoxyglucose F18/*chemistry ; Glucose/*metabolism ; Humans ; Male ; Middle Aged ; *Positron-Emission Tomography ; Propranolol/pharmacology/therapeutic use ; Radiopharmaceuticals/*chemistry