Experimental Demonstration of Hadron Beam Cooling Using Radio-Frequency Accelerated Electron Bunches.

Cooling of beams of gold ions using electron bunches accelerated with radio-frequency systems was recently experimentally demonstrated in the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. Such an approach is new and opens the possibility of using this technique at higher energies than possible with electrostatic acceleration of electron beams. The challenges of this approach include generation of electron beams suitable for cooling, delivery of electron bunches of the required quality to the cooling sections without degradation of beam angular divergence and energy spread, achieving the required small angles between electron and ion trajectories in the cooling sections, precise velocity matching between the two beams, high-current operation of the electron accelerator, as well as several physics effects related to bunched-beam cooling. Here we report on the first demonstration of cooling hadron beams using this new approach.

Trends in hip fracture rates in Taiwan: a nationwide study from 1996 to 2010.

There was an initial increase and a later decrease in hip fracture rates in Taiwan between 1996 and 2010 (457.9 to 390.0 fractures per 100,000 people per year). Mortality rates decreased but re-emerged later (2.26 to 1.91 deaths per 100 hip fracture admissions). The turning point for change in trends was 2003. INTRODUCTION: Fractures of the proximal femur remain a major cause of mortality and morbidity. We aimed to examine recent trends in hip fracture rates, in-hospital mortality rates, and length of hospital stay (LOS) due to hip fractures in people aged 55 and over in Taiwan. METHODS: This is a time-trend study. We used data from the National Health Insurance Research Database between 1996 and 2010 in Taiwan. Insurants aged 55 and over were included. The outcome measures were age-adjusted hip fracture rates, age-adjusted in-hospital mortality rates, and LOS due to hip fractures. We classified hip fractures into femoral neck, trochanteric, and subtrochanteric fractures. RESULTS: We identified 250,919 hospitalizations for hip fractures. The total number of hip fractures increased steadily from 12,479 to 19,841 cases. There was a trend towards initial increase and then later decrease in hip fracture rates (from 457.9 to 390.0 fractures per 100,000 people per year). LOS decreased by 46.5 % (17.53 to 9.38 days). By contrast, mortality rates for hip fractures decreased initially, but re-emerged later with a total decrement of 15.5 % (2.26 to 1.91 deaths per 100 hip fracture admissions). Women outnumbered men in all types of hip fractures, but men had higher in hospital mortality rates. LOS was similar between genders and among age groups. The turning point for change in trends was year 2003. CONCLUSIONS: While LOS shortened gradually since 1996, the absolute number of hip fractures in Taiwan continues to rise. There is still room for improvement in reducing mortality due to hip fractures.

Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

Higher rate of colorectal cancer among patients with pyogenic liver abscess with Klebsiella pneumoniae than those without: an 11-year follow-up study.

AIM: Pyogenic liver abscess (PLA) has been reported as an early manifestation of colorectal cancer (CRC) in adults, but few studies have investigated this relationship. It is unclear if patients with Klebsiella pneumoniae PLA are at increased risk of subsequent CRC. Our aims were to estimate the incidence of CRC among patients with PLA and to compare the incidence of CRC between K. pneumoniae PLA and non-K. pneumoniae PLA groups. METHOD: We conducted a retrospective study of patients with PLA diagnosed between 2000 and 2009 at a medical centre in northern Taiwan. CRC status and survival status were determined until December 2010. Incidence data from the general population were retrieved from the Taiwan Cancer Registry. Outcome measures were defined as standardized incidence ratio and the incidence rate per 100,000 person-years. RESULTS: This study included 2294 patients, of whom 1194 (52%) had K. pneumoniae infection. During the follow-up period, 54 (2.3%) patients were diagnosed with CRC, corresponding to an overall incidence rate of 669.1 (95% CI, 490.7-847.6) per 100,000 person-years. The adjusted hazard ratio of CRC was 2.68 times greater for patients with K. pneumoniae PLA than for those with non-K. pneumoniae PLA (95% CI, 1.40-5.11). CONCLUSION: Patients with K. pneumoniae PLA had a significantly higher rate of subsequent CRC than did patients with non-K. pneumoniae PLA. Colonoscopy is recommended to detect occult colonic malignancy in patients with PLA, particularly for patients over 60 years of age and with K. pneumoniae.

Evaluation of dual-mode rainwater harvesting system to mitigate typhoon-induced water shortage in Taiwan.

The water shortage of today's world is one of the most challenging problems and the world is looking for the best solution to reduce it. Some human made causes and also natural causes are liable for the shortage of the existing water supply system. In Taiwan, especially during typhoon, the turbidity of raw water increases beyond the treatment level and the plant cannot supply required amount of water. To make the system effective, a couple of days are needed and the shortage occurs. The purpose of this study is to solve this emergency shortage problem. A dual-mode Rainwater Harvesting System (RWHS) was designed for this study as a supplement to the existing water supply system to support some selected non-potable components such as toilet and urinal flushing of an elementary school. An optimal design algorithm was developed using YAS (yield after spillage) and YBS (yield before spillage) release rules. The study result proved that an optimum volume of tank can solve the emergency water shortage properly. The system was found to be more reliable in Taipei area than that of Tainan area. The study also discovered that a government subsidy would be needed to promote the system in Taiwan.

A cell culture model of the blood-brain barrier.

Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.

Symptoms and signs of port-related infections in oncology patients related to the offending pathogens.

AIM: There is limited information about symptoms and signs of port-related infections linking to their offending pathogens. METHODS: Oncology patients proven to have port-related infections were retrospectively analysed. We divided them into two subgroups according to their symptoms and signs. Onset of fever and chills with or without hypotension following the port flush was classified as 'port flush form infection'. Presence of local inflammatory signs, including erythema, warmth, tenderness and pus formation and systemic infection signs, including fever, chills with or without hypotension was classified as 'local inflammatory form infection'. RESULTS: There were 29 episodes of port-related infection among 28 patients, with port flush form 22 episodes and local inflammatory form seven episodes. Of 22 episodes of port flush form infections, 20 (91%) were nosocomial glucose non-fermenting gram-negative bacilli, with Acinetobacter baumannii (11 episodes, 50%) and Enterobacter cloacae (four episodes, 18%) the most common. Polymicrobial infections occurred in four episodes (18%). Candida infection occurred in two episodes (9%). Of seven episodes of local inflammatory form infections, six (86%) were gram-positive cocci, with Staphylococcus aureus (five episodes, 71%) the most common. The time from port implantation to its infection was 272 +/- 255 days (30-993 days) for the port flush form infections and 82 +/- 87 days (22-265 days) for the local inflammatory form infections. This difference was not significant difference (p = 0.068). CONCLUSIONS: The differences between infection of patients with port flush form and local inflammatory form in incidence and offending microorganism suggest that the aetiology of infection were different.

Effect of central administration of QRFP(26) peptide on energy balance and characterization of a second QRFP receptor in rat.

The recently identified neuropeptide QRFP(26) is predominantly expressed in the hypothalamus and was suggested to play a role in the regulation of food intake following the observation of an acute orexigenic effect after central administration in mice. QRFP(26) exerts its effect via GPR103 and a newly identified receptor in mouse. The aim of our study was (a) to investigate the distribution of QRFP(26) and a newly discovered QRFP receptor mRNA in rat and (b) to further characterize the effects of central administration of QRFP(26) on energy balance in rats. QRFP(26) mRNA was detected in the retrochiasmatic nucleus, periventricular nucleus, arcuate nucleus and restricted areas of the lateral nucleus of the hypothalamus. We found an additional receptor with high homology for GPR103 in rat. This receptor increases inositol triphosphate production in transfected cells in presence of QRFP(26) and its mRNA was particularly enriched in ventral and posterior thalamic groups, anterior hypothalamus and medulla. When QRFP(26) (10 microg and 50 microg) was administered centrally before the start of the light phase both doses increased food intake for 2 h after injection without reaching statistical significance. QRFP(26) caused no changes in locomotor activity or energy expenditure. In summary, central QRFP(26) injection causes slight and transient hyperphagia in rats without changing any other energy balance parameters after 24 h. We conclude that QRFP(26) has limited impact on the central regulation of energy balance in rats and that its essential function remains to be clarified.

Localization of agonist- and antagonist-binding domains of human corticotropin-releasing factor receptors.

The CRF receptors, CRFR1 and CRFR2, are members of the G protein-coupled receptor superfamily. Despite their considerable sequence similarity, CRFR1 and CRFR2 have quite different affinities for the peptide ligand rat/human CRF. Previous studies using chimeric receptors between human CRFR1 and CRFR2 have identified three potentially important regions in the second and third extracellular domains of CRF receptor for the binding of rat/human CRF. The present report further demonstrates that these same three regions also affect the binding of urocortin and sauvagine, two other members of the CRF peptide family, albeit to different extents. We also show that a fourth region in the third extracellular domain, Asp254, has been identified to be important for sauvagine but not CRF or urocortin binding. Thus, the three peptide ligands not only interact with a different set of regions on CRFR1 and CRFR2 but also differentially interact with some of the same regions. These data could, at least in part, account for the much higher affinity of CRFR2 for urocortin and sauvagine compared with rat/human CRF. We have also identified two amino acid residues, His199 in the third transmembrane domain and Met276 in the fifth transmembrane domain, that are important for binding the non-peptide high-affinity CRFR1 antagonist NBI 27914. Mutations of His199 and Met276 to the corresponding amino acids in CRFR2 each decreased the binding affinity of NBI 27914 for CRFR1 by 40- and 200-fold, respectively. This suggests that the transmembrane regions are critically important in forming the binding pocket for the nonpeptide antagonist.

Localization of ligand-binding domains of human corticotropin-releasing factor receptor: a chimeric receptor approach.

Two CRF receptors, CRFR1 and CRFR2, have recently been cloned and characterized. CRFR1 shares 70% sequence identity with CRFR2, yet has much higher affinity for rat/human CRF (r/hCRF) than CRFR2. As a first step toward understanding the interactions between rat/human CRF and its receptor, the regions that are involved in receptor-ligand binding and/or receptor activation were determined by using chimeric receptor constructs of the two human CRFR subtypes, CRFR1 and CRFR2, followed by generating point mutations of the receptor. The EC50 values in stimulation of intracellular cAMP of the chimeric and mutant receptors for the peptide ligand were determined using a cAMP-dependent reporter system. Three regions of the receptor were found to be important for optimal binding of r/hCRF and/or receptor activation. The first region was mapped to the junction of the third extracellular domain and the fifth transmembrane domain; substitution of three amino acids of CRFR1 in this region (Val266, Tyr267, and Thr268) by the corresponding CRFR2 amino acids (Asp266, Leu267, and Val268) increased the EC50 value by approximately 10-fold. The other two regions were localized to the second extracellular domain of the CRFR1 involving amino acids 175-178 and His189 residue. Substitutions in these two regions each increased the EC50 value for r/hCRF by approximately 7- to 8-fold only in the presence of the amino acid 266-268 mutation involving the first region, suggesting that their roles in peptide ligand binding might be secondary.

Cloning and characterization of the human corticotropin-releasing factor-2 receptor complementary deoxyribonucleic acid.

Two CRF receptor subtypes (CRF1 and CRF2 receptors) with distinct brain localizations and pharmacological profiles have recently been cloned and characterized. For the CRF2 receptor subtype, at least 2 splice forms with different 5'-coding sequences (CRF2 alpha and CRF2 beta) have been identified in rat. In this article, we report the genomic structure and the corresponding complementary DNA (cDNA) sequence of the human CRF2 receptor. The gene coding for human CRF2 receptor consists of at least 12 exons and spans approximately 30 kilobases. The cDNA sequence in the protein-coding region is 94% identical to that of the reported rat CRF2 alpha receptor. At present, there is no evidence for the existence of a CRF2 beta receptor homolog in humans. The encoded receptor is 411 amino acids in length and is 70% identical to the human CRF1 receptor, with least sequence homology in the N-terminal extracellular domain (47% identical). Cells transfected with the full-length human CRF2 receptor cDNA responded to rat/human CRF and sauvagine by increasing the intracellular cAMP level, with EC50 values of approximately 20 and 1 nM, respectively. The CRF- and sauvagine-induced accumulation of intracellular cAMP could be competitively inhibited by the CRF receptor antagonist D-Phe-CRF. This pharmacological profile was comparable to that of the rat CRF2 alpha receptor. The relative abundance of the CRF2 receptor messenger RNA appears to be lower in humans than in rats for the tissues studied thus far.

Paradoxical effects of cycloheximide on the ultra-rapid induction of two hepatic mRNA sequences by triiodothyronine (T3).

Triiodothyronine (T3) rapidly induces the accumulation of two hepatic mRNA sequences (spot 14 and spot CyT) in thyroidectomized rats as revealed by two-dimensional gel electrophoresis of in vitro translated products of isolated poly(A) containing RNA. T3 acting alone induced a 29-fold increase of spot 14 within 4 h, an increase which was completely inhibited by the concomitant administration of cycloheximide. On the other hand, CyT could be detected only after the administration of cycloheximide, and the combined action of cycloheximide and T3 resulted in a 4-fold increase in CyT 4 h after administration of both agents. These observations suggested that the early cellular action of T3 is contingent on the participation of rapidly turning over protein and mRNA.

Prognostic factors of nasopharyngeal carcinoma: a multivariate analysis.

Between 1979 and 1985, 561 patients with nasopharyngeal carcinoma were reviewed to determine prognostic factors that may influence survival. Sex (p = 0.294) and histopathology (p = 0.677) had no correlation to the actuarial survival, whereas the site of cervical metastasis (p = 0.001) and the radiation doses to the nasopharynx and regional lymph nodes (p = 0.03) were both significant when one used univariate analyses. Cox's multivariate regression model revealed that the presence rather than the site of distant metastases was the single most important independent factor influencing the treatment outcome (p less than 0.0001). The addition of chemotherapy, on the other hand, did not show a survival benefit even when one took available confounding factors into account. There are, however, survival advantages associated with: (a) young age (less than or equal to 40 years), (b) asymptomatic status, (c) Stage I or II lesions, and (d) biopsy via nasopharynx instead of neck nodes. These favorable prognostic factors may be used for therapeutic guidance and end-result reporting.

Molecular and functional characterization of recombinant human metabotropic glutamate receptor subtype 5.

We have isolated and characterized overlapping cDNAs that encode two isoforms of the human metabotropic glutamate receptor subtype 5 (hmGluR5). The deduced amino acid sequences of human and rat mGluR5a are 94.5% identical. However, a region in the putative cytoplasmic domain (SER926-ALA1121) displays significant sequence divergence. Genomic analysis of this region showed that the sequence divergence results from species-specific differences in the genomic sequences, not from alternative splicing. The distribution of mGluR5 mRNA in human brain was most strongly detected throughout the hippocampus, with moderate levels in the caudate-putamen, cerebral cortex, thalamus, and deep cerebellar nuclei, and at low levels in the cerebellar cortex. Activation of both hmGluR5a and hmGluR5b transiently expressed in Xenopus oocytes and HEK293 cells was coupled to inositol phosphate (InsP) formation and elevation of the intracellular free calcium ([Ca2+]i). The agonist rank order of potency for activating recombinant hmGluR5a receptors in either system was quisqualate > L-glutamate > 1S,3R-ACPD. Both the quisqualate stimulated InsP and [Ca2+]i were inhibited by (+)-MCPG. Recombinant human mGluR5a was also stably expressed in mouse fibroblast Ltk- cells, in which the efficacy and potency of quisqualate were unchanged for more than 30 cell passages.

Cloning of a cDNA encoding a novel interleukin-1 receptor related protein (IL 1R-rp2).

We have identified and isolated both the rat and human cDNAs for a novel putative receptor related to the interleukin-1 type 1 receptor. We have named this protein interleukin 1 receptor related protein two (IL 1R-rp2). The rat cDNA for IL1R-rp2 was first identified using oligonucleotides of degenerate sequence in a polymerase chain reaction (PCR) paradigm with rat brain mRNA as the template. The protein encoded by both of these cDNAs are 561 amino acids long and exhibit 42% and 26% overall identity with the interleukin-1 type 1 and type 2 receptors, respectively. RNase protection assays from rat tissues revealed a predominant expression for IL 1R-rp2 in the lung and epididymis with lower levels detected in the testis and cerebral cortex. By in situ hybridization we were able to determine that the expression in rat brain appeared to be non-neuronal and associated with the cerebral vasculature. When expressed transiently in COS-7 cells the receptor was incapable of high affinity binding to either [125I]-recombinant human IL 1 alpha or [125I]-recombinant human IL 1 beta. Together, these data demonstrate the existence of a novel protein that is related to the interleukin-1 receptor but does not bind IL-1 by itself.

Inhibition by amphetamine of testosterone secretion through a mechanism involving an increase of cyclic AMP production in rat testes.

1. The effect of amphetamine on the secretion of testosterone and the production of testicular adenosine 3':5'-cyclic monophosphate (cyclic AMP) in rats was studied. 2. A single intravenous injection of amphetamine decreased the basal and human chorionic gonadotropin (hCG)-stimulated levels of plasma testosterone. Plasma LH levels were not altered by the injection of amphetamine. 3. Administration of amphetamine in vitro resulted in a dose-dependent inhibition of both basal and hCG-stimulated release of testosterone. 4. Amphetamine enhanced the basal and hCG-increased levels of cyclic AMP accumulation in vitro in rat testes. 5. These results suggest that amphetamine inhibits the spontaneous and hCG-stimulated secretion of testosterone from the testes through a mechanism involving an increase in cyclic AMP production.

Colorimetric assay for rapid screening of corticotropin releasing factor receptor ligands.

The corticotropin releasing factor (CRF) receptor is known to be coupled to Gs and transduces its signal through stimulation of cyclic AMP (cAMP) production. Here we describe the characterization of several stable CRF receptor-expressing LVIP2.0Zc cell lines that also contain an exogenous cAMP-responsive beta-galactosidase reporter gene construct. The CRF receptor activity was assayed by measuring the induction of beta-galactosidase in response to CRF. Rat/human and bovine CRF stimulated beta-galactosidase activity in a dose-dependent manner with EC50 values of approximately 0.1 nM; the biologically weak deamidated analog of bovine CRF was approximately 500-fold less potent. The CRF receptor antagonist, [d-Phe12,Nle21,38,Ala32]r/hCRF(12-41) produced a dose-dependent inhibition of CRF-stimulated beta-galactosidase activity, further demonstrating the pharmacological specificity of the interaction. The magnitude of the maximal response to CRF varied among individual cell lines. This variation was independent of the level of CRF receptor expression, but reflected differences in the intrinsic activity of adenylate cyclase. In contrast to most cAMP assay systems, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine decreased the CRF-induced beta-galactosidase activity when used in the context of the assay regimen described here. Since the assay can be easily performed in a high-throughput 96-well plate format, these cell lines provide an efficient way for the identification of CRF receptor agonists and antagonists.

Control of cisplatin-induced emesis with intravenous ondansetron plus intravenous dexamethasone: a crossover study of triple 8-mg dose of ondansetron.

Two hundred seventy-five patients were enrolled in one of two arms in a crossover fashion. Arm A: three 8-mg doses of ondansetron intravenous (IV) were given at 4-hour intervals plus dexamethasone 20 mg IV from the start of chemotherapy followed by dexamethasone 5 mg IV every 12 hours. Arm B: as in arm A but with three 8-mg doses of ondansetron IV were given at 24-hour intervals substituted for ondansetron IV given at 4-hour intervals. There were 237 patients in arm A and 223 patients in arm B. Complete protection from acute and delayed vomiting/nausea obtained in arm A was 94.5%/90.3% and 71.3%/57.8%, respectively; protection obtained in arm B was 92.7%/91.0% and 71.7%/60.5%, respectively. No differences were observed in control of acute emesis after the addition of dexamethasone to ondansetron, given as either a triple 8-mg dose at 4-hour intervals or a single 8-mg dose. The triple dose of ondansetron given at 24-hour intervals was also not more effective than ondansetron given at 4-hour intervals in preventing delayed emesis when dexamethasone was added. However, the former improved control of delayed nausea on day 2. Adverse events tended to be minor, with constipation and hiccup the most common.

Tumor fever in patients with nasopharyngeal carcinoma: clinical experience of 67 patients.

From 1982 through 1996, 67 patients with nasopharyngeal carcinoma (NPC) proven to have tumor fever (TF) were analyzed. All were in metastatic stage when TF occurred. Forty-five patients (67%) had recurrent disease. Thirty-eight (57%) had fever before metastatic lesions were detected. The metastatic sites were: 84% in bone, 69% in liver, and 19% in lung. Multiple-organ metastases were found in 64% of the patients. Nine patients (13%) had bone-marrow invasion. When TF was present, 22 (33%) patients had other paraneoplastic syndromes, of which leukemoid reaction (LR) was seen most frequently. After the initiation of naproxen or indomethacin, most patients had complete lysis of the fever within 48 hours. Of the six patients receiving chemotherapy as the initial therapy, all of their temperatures returned to normal range after the treatment. Some patients, particularly those with tumor progression, developed TF again when antipyretic drugs were discontinued. The median survival time was 5 months. In conclusion, TF in NPC is usually a manifestation of metastatic disease. Tumor fever often associates with other paraneoplastic syndromes. Naproxen, indomethacin, and systemic chemotherapy all had effectiveness in ameliorating TF. Systemic metastases should be suspected in NPC patients with fever of unknown origin.

Prognostic factors of locoregionally recurrent nasopharyngeal carcinoma--a retrospective review of 182 cases.

Locoregional relapse is the major cause of failure of nasopharyngeal carcinoma (NPC) after radical radiation therapy. The prognosis of such patients is dismal, and the factors related to the outcome are not well identified. Between January 1983 and December 1989, 1,168 new patients with biopsy-proven NPC were seen at this hospital. Eight hundred and eighty-three of these patients were treated uniformly with radical external irradiation and intracavitary treatment with or without chemotherapy. The clinical courses, retreatment outcomes, and prognostic factors for locoregional relapse and subsequent distant metastasis were analyzed. During the follow-up period of 3-10 years or until death, 182 patients (20.6%) developed locoregional relapses without distant metastasis initially. T stage and age were significant prognostic factors for locoregional recurrence. In contrast, histopathologic subtype, N stage, sex, and systemic chemotherapy were not. There were 36 patients (19.8%) who developed subsequent distant metastasis with or without retreatment. The median time from locoregional relapses to distant metastasis was 6 months in this study, and bone was the most frequent and the earliest site of distant metastasis. The N stage at diagnosis, the initial disease-free interval, the presence of neck nodal disease at relapse, and age were the significant factors for predicting the subsequent distant metastasis in locoregionally recurrent NPC patients. We recommend that additional systemic chemotherapy should be considered for retreatment of locoregional relapsed NPC, not only for enhancement of local control but also for eradicating microscopic metastasis as anticipated.