PubMed Health⌕ Search

Biomedical subjects

Young-Ho Kim

Publications and source records attributed to Young-Ho Kim.

At least 19 recordsLinked to original sources

TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation.

TNF-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapy that preferentially induces apoptosis in cancer cells. However, many neoplasms are resistant to TRAIL by mechanisms that are poorly understood. Here we demonstrated that human prostate cancer cells, but not normal prostate cells, are dramatically sensitized to TRAIL-induced apoptosis and caspase activation by quercetin. Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells. We have shown that quercetin can potentiate TRAIL-induced apoptotic death. Human prostate adenocarcinoma DU-145 and LNCaP cells were treated with various concentrations of TRAIL (10-200 ng/ml) and/or quercetin (10-200 microM) for 4 h. Quercetin, which caused no cytotoxicity by itself, promoted TRAIL-induced apoptosis. The TRAIL-mediated activation of caspase, and PARP (poly(ADP-ribose) polymerase) cleavage were both enhanced by quercetin. Western blot analysis showed that combined treatment with TRAIL and quercetin did not change the levels of TRAIL receptors (death receptors DR4 and DR5, and DcR2 (decoy receptor 2)) or anti-apoptotic proteins (FLICE-inhibitory protein (FLIP), inhibitor of apoptosis (IAP), and Bcl-2). However, quercetin promoted the dephosphorylation of Akt. Quercetin-induced potent inhibition of Akt phosphorylation. Taken together, the present studies suggest that quercetin enhances TRAIL-induced cytotoxicity by activating caspases and inhibiting phosphorylation of Akt.

Apoptosis↗

Mechanical loading of rigid intramuscular implants.

Several groups are developing different versions of a new class of leadless, permanently implanted electronic devices with a size and form factor that allows them to be injected into muscles (BIONs). Their circuitry is protected from body fluids by thin-walled hermetic capsules made from rigid and brittle materials (glass or ceramic) that include feedthroughs to their electrodes. These packages experience repetitive stresses from the very contractions that they excite. We here provide a worst-case analysis of such stresses and methods for testing and validation of devices intended for such usage, along with the failure analysis and remediation strategy for a design that experienced unanticipated failures in vivo.

Compressive Strength↗

Effects of PGC-1alpha on TNF-alpha-induced MCP-1 and VCAM-1 expression and NF-kappaB activation in human aortic smooth muscle and endothelial cells.

Increased oxidative stress in vascular cells is implicated in the pathogenesis of atherosclerosis. Reactive oxygen species (ROS) induce vascular inflammation via the proinflammatory cytokine/NF-kappaB pathway. Several lines of evidence suggest that peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha) is an important regulator of intracellular ROS levels. However, no studies have examined the effects of PGC-1alpha on this process. We investigated the effects of PGC-1alpha on inflammatory molecule expression and activity of the redox-sensitive transcription factor, NF-kappaB, in vascular cells. PGC-1alpha expressed in human aortic smooth (HASMCs) and endothelial cells (HAECs) is upregulated by AMP-activated protein kinase activators, including metformin, rosiglitazone and alpha-lipoic acid. Tumor necrosis factor-alpha (TNF-alpha), a major proinflammatory factor in the development of vascular inflammation, stimulates intracellular ROS production through an increase in both mitochondrial ROS and NAD(P)H oxidase activity. Adenovirus-mediated overexpression of the PGC-1alpha gene in HASMCs and HAECs leads to a significant reduction in intracellular and mitochondrial ROS production as well as NAD(P)H oxidase activity. Consequently, NF-kappaB activity and MCP-1 and VCAM-1 induced by TNF-alpha are suppressed. Our data support the possibility that agents stimulating PGC-1alpha expression in the vasculature aid in preventing the development of atherosclerosis.

Aorta, Thoracic↗

Time sequence of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cisplatin treatment is responsible for a complex pattern of synergistic cytotoxicity.

The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cisplatin resulted in a greater cytotoxicity than could be accounted for by the addition of the cytotoxic effects of the agents alone. In this study, we hypothesized that the synergistic interaction between the two modalities can be changed when both the sequence and the time interval between the two treatments are varied. To test the hypothesis, human head-and-neck squamous-cell carcinoma (HNSCC)-6 cells were either pretreated with 0.01-0.5 microg/ml TRAIL for various times (0-24 h) followed by treatment with 5 microg/ml cisplatin or pretreated with 5 microg/ml cisplatin for various times (0-24 h) followed by treatment with 0.5 microg/ml TRAIL. In latter case, the synergistic effect was gradually increased when the time interval between the two treatments was increased. In former case, a maximal synergy occurred within 0-4 h of pretreatment with TRAIL. However, the synergistic effect was gradually decreased when the time interval between the two treatments was increased. Data from immunoblotting analysis reveal that a similar pattern emerged for the PARP cleavage and caspase activation. The synergistic effect is not associated with DR4, DR5, FADD, and FLIP(L). Interestingly, a complex pattern of synergistic interaction between TRAIL and cisplatin is related to the cleavage of FLIP(S). Although overexpression of FLIP(S) protected cells from FLIP(S) cleavage and apoptotic death, blockage of FLIP(S) cleavage by replacing Asp(39) and Asp(42) residues with alanine did not further enhance FLIP(S)-mediated protection. Taken together, FLIP(S) cleavage reflects apoptotic damage, but it does not cause apoptosis.

Amino Acid Sequence↗

Current clinical propensity of laryngeal tuberculosis: review of 60 cases.

Although laryngeal tuberculosis is not frequent, it still occurs with an increasing incidence of pulmonary tuberculosis. Clinical pattern and spread mechanism of this disease have also changed as well. This study was performed to examine the current propensity seen in laryngeal tuberculosis and the clinical characteristics of this disease in patients showing atypical clinical pattern. The medical and videostroboscopic records of 60 patients with laryngeal tuberculosis diagnosed from the year 1994 to 2004 at the department of otorhinolaryngology in Severance Hospital were analyzed. The age of the patients ranged from 25 to 78 years, with their average age being 49.7 years. The ratio between men and women was 1.9:1. The major symptom encountered was hoarseness (96.6%). Clinically, granulomatous (n=22) and ulcerative types (n=11) of laryngeal tuberculosis were still prevalent, however, the incidence of atypical types such as polypoid (n=16) and nonspecific (n=11) were on the rise. Among the 27 cases that showed polypoid or nonspecific types, unilateral lesion was seen in 20 cases (74%). The most frequently affected area by this disease was true vocal cord, followed by false vocal cord, epiglottis, arytenoids and posterior commissure. Active pulmonary tuberculosis was present in 28 (46.7%), inactive pulmonary tuberculosis in 20 (33.3%), normal lung status in 12 cases (20%). Primary laryngeal tuberculosis was present in 9 cases (15%). Single lesion, polypoid and nonspecific type were prevalent in patients with inactive tuberculosis or normal lungs status. Physicians should be aware of the changes in the clinical pattern of laryngeal tuberculosis, which poses serious complications and risk of spreading.

Adult↗

The 5'-end transitional CpGs between the CpG islands and retroelements are hypomethylated in association with loss of heterozygosity in gastric cancers.

BACKGROUND: A loss of heterozygosity (LOH) represents a unilateral chromosomal loss that reduces the dose of highly repetitive Alu, L1, and LTR retroelements. The aim of this study was to determine if the LOH events can affect the spread of retroelement methylation in the 5'-end transitional area between the CpG islands and their nearest retroelements. METHODS: The 5'-transitional area of all human genes (22,297) was measured according to the nearest retroelements to the transcription start sites. For 50 gastric cancer specimens, the level of LOH events on eight cancer-associated chromosomes was estimated using the microsatellite markers, and the 5'-transitional CpGs of 20 selected genes were examined by methylation analysis using the bisulfite-modified DNA. RESULTS: The extent of the transitional area was significantly shorter with the nearest Alu elements than with the nearest L1 and LTR elements, as well as in the extragenic regions containing a higher density of retroelements than in the intragenic regions. The CpG islands neighbouring a high density of Alu elements were consistently hypomethylated in both normal and tumor tissues. The 5'-transitional methylated CpG sites bordered by a low density of Alu elements or the L1 and LTR elements were hypomethylated more frequently in the high-level LOH cases than in the low-level LOH cases. CONCLUSION: The 5'-transitional methylated CpG sites not completely protected by the Alu elements were hypomethylated in association with LOH events in gastric cancers. This suggests that an irreversible unbalanced decrease in the genomic dose reduces the spread of L1 methylation in the 5'-end regions of genes.

5' Flanking Region↗

Application of the transtheoretical model to identify psychological constructs influencing exercise behavior: a questionnaire survey.

BACKGROUND: Current research on exercise behavior has largely been attempted to identify the relationship between psychological attributes and the initiation or adherence of exercise behavior based on psychological theories. A limited data are available on the psychological predictors of exercise behavior in public health. OBJECTIVES: The present study examined the theorized association of TTM of behavior change constructs by stage of change for exercise behavior. METHODS: A total of 228 college students selected from 2 universities in Seoul were surveyed. Four Korean-version questionnaires were used to identify the stage of exercise behavior and psychological attributes of adolescents. Data were analyzed by frequency analysis, MANOVA, correlation analysis, and discriminant function analysis. RESULTS: Multivariate F-test indicated that behavioral and cognitive processes of change, exercise efficacy, and pros differentiated participants across the stages of exercise behavior. Furthermore, exercise behavior was significantly correlated with the TTM constructs, and that overall classification accuracy across the stages of change was 61.0%. CONCLUSIONS: The present study supports the internal and external validity of the Transtheoretical Model for explaining exercise behavior. As this study highlights, dissemination must increase awareness but also influences perceptions regarding theoretically based and practically important exercise strategies for public health professionals.

Adolescent↗

A gene encoding phosphatidyl inositol-specific phospholipase C from Cryphonectria parasitica modulates the lac1 expression.

Hypovirus infection of the chestnut blight fungus Cryphonectria parasitica is known to downregulate the fungal laccase1 (lac1), the modulation of which is tightly governed by the inositol triphosphate (IP(3)) and calcium second messenger system in a virus-free strain. We cloned the gene cplc1 encoding a phosphatidyl inositol-specific phospholipase C (PLC), to investigate the regulation of lac1 expression and to better characterize fungal gene regulation by hypovirus. Sequence analysis of the cplc1 gene indicated that the protein product contained both the X and Y domains, which are the two conserved regions found in all known PLCs, with a 133 amino acid extension between the 2nd beta-strand and the alpha-helix in the X domain. In addition, the gene organization appeared to be highly similar to that of a delta-type PLC. Disruption of the cplc1 gene resulted in slow growth and produced colonies characterized by little aerial mycelia and deep orange in color. Accordingly, reduced virulence of the cplc1-null mutant as compared to the wild-type was observed, which can be ascribed to the growth defect. However, other PLC-associated characteristics including temperature sensitivity and osmosensitivity did not differ from the wild-type strain. Northern blot analysis revealed no accumulation of the lac1 gene transcript due to the disruption of the cplc1 gene. Functional complementation of the cplc1-null mutant with the PLC1 gene from Saccharomyces cerevisiae restored lac1 expression, which suggests that the cloned gene encodes PLC activity. The present study indicates that the cplc1 gene is required for normal mycelial growth rate and colony morphology, and that it regulates the lac1 expression, which is also modulated by the hypovirus. Although several PLC genes have been identified in various simple eukaryotic organisms, the deletion analysis of the cplc1 gene in this study appears to be the first report on the functional analysis of PLC in filamentous fungi.

Amino Acid Sequence↗

The length of CpG islands is associated with the distribution of Alu and L1 retroelements.

Alu and L1 retroelements have been suggested to initiate the spread of CpG methylation. In this study, the spread of CpG methylation was estimated based on the distance between the CpG islands and the nearest retroelements. All human genes (23,116) were examined and the correlations between the length of the CpG islands and the distance and density of the confronting retroelements were examined using nonoverlapping 5-kb windows. There was a linear relationship between the length of the CpG islands and the density of the Alu elements and an inverse relationship between the CpG islands and the L1 elements located more distantly, suggesting a suppressive effect of the Alu's on the spread of L1 methylation. Methylation analysis of the transitional CpG sites between the CpG islands and the nearest retroelements upstream of 16 genes was then carried out using DNA preparations from 11 different human tissues. Methylation-variable transitional CpGs were observed for the selected genes and the different tissues.

Alu Elements↗

Suppression of Egr-1 transcription through targeting of the serum response factor by oncogenic H-Ras.

The transcription factor Egr-1 functions as a key regulator in cellular growth, differentiation, and apoptosis. The loss of Egr-1 expression is closely associated with tumor development, although the molecular mechanism behind the suppression of Egr-1 is largely unknown. In this report, we show that growth factor-induced transcriptional activation of Egr-1 gene is downregulated by chronic expression of oncogenic H-Ras in NIH3T3 fibroblasts. Our results demonstrate that phosphoinositide 3-kinase (PI3K) signaling is necessary for oncogenic H-Ras-mediated reduction of Egr-1 gene expression. Aberrant activation of PI3K signaling by oncogenic Ras decreased the level of serum response factor (SRF) protein through the acceleration of proteolysis, which resulted in decreased SRF binding to the serum response element (SRE) sites within the Egr-1 promoter, leading to the suppression of Egr-1 transcription. Inhibition of PI3K signaling restored the downregulation of SRF and Egr-1 expression caused by oncogenic Ras. Our findings suggest a novel signaling mechanism by which prolonged activation of oncogenic H-Ras can trigger the loss of tumor suppressor Egr-1 through the PI3K pathway in NIH3T3 fibroblast model cell lines.

3T3 Cells↗

Downregulation of protein kinase CKII is associated with cellular senescence.

Protein kinase CKII (CKII) plays a critical role in cell growth and proliferation. In this study, we examine how CKII activity is regulated during cellular senescence. Our results demonstrate that CKII activity apparently decreases during both replicative and H2O2-induced senescence in human diploid fibroblast IMR-90 cells. The mRNA and protein levels of CKIIalpha decreases significantly during replicative and H2O2-induced senescence, while only slight reduction in those of CKIIbeta is observed during replicative senescence. Treatment of IMR-90 cells with CKII inhibitors 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole and apigenin led cells to acquire a senescent phenotype as judged by the senescence-associated beta-galactosidase marker and overexpression of p53 and p21(Waf-1). Knockdown of CKIIalpha in IMR-90 cells by RNA interference also dramatically induced the senescent phenotype. In parallel, CKII activity was transcriptional downregulated in rat liver and testis with advancing age. Taken together, these results suggest that downregulation of CKII activity is tightly associated not only with cellular senescence but also with organism aging.

Aging↗

Inhibition of trypsin-induced mast cell activation by acanthoic acid.

Acanthoic acid (AA) is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum (Araliaceae). In the present study, we examined whether AA has the inhibitory effect on the production of inflammatory mediators and activating signals induced in trypsin-treated human leukemic mast cell-1 (HMC-1). HMC-1 cells were stimulated with trypsin (100 nM) in the presence or absence of AA (1, 10, and 100 microg/ml). We assessed the production of TNF-alpha and tryptase by enzyme-linked immunosorbent assay (ELISA) or reverse transcription-PCR, ERK activation by Western blot, and NF-kappaB activation by gel shift assay. AA (10 and 100 microg/ml) significantly inhibited production of both TNF-alpha and tryptase in a dose-dependent manner in trypsin-stimulated HMC-1. Furthermore, AA inhibited ERK phosphorylation and NF-kappaB activation induced by trypsin treatment without blocking of trypsin activity even with 100 microg/ml. These results suggest that AA may inhibit the production of inflammatory mediators through inhibition of ERK phosphorylation and NF-kappaB activation pathway in human mast cells. It supports the evidence that AA may be used to blocks the development of inflammation caused from mast cells.

Cells, Cultured↗

Lymphatic metastases to level IIb in hypopharyngeal squamous cell carcinoma.

OBJECTIVES: To evaluate the prevalence of level IIb lymph node (LN) metastasis and to identify potential clinical risk factors when level IIb metastatic diseases are present in patients with clinically node-negative (N0) and node-positive (N+) necks with hypopharyngeal squamous cell carcinoma (HPSCC). This will provide a basis for determining whether this region can be excluded in elective or therapeutic neck dissection in patients with HPSCC. DESIGN: Prospective analysis of a case series. SETTING: University hospital. PATIENTS: Fifty patients with HPSCC who underwent surgical treatment for a primary lesion and simultaneous neck dissection from January 1998 to February 2004. MAIN OUTCOME MEASURES: The incidences and clinical risk factors for level IIb LN metastasis and regional recurrence according to the presence or absence of pathologic LN involvement in level IIb. RESULTS: A total of 93 neck dissections were analyzed in this study. Of these dissections, 59 (63%) were elective and 34 (37%) were therapeutic. Three percent (2 of 59) of all N0 necks and 32% (11 of 34) of all N+ necks had level IIb LN metastases. Level IIb nodal metastases were significantly more prevalent in N+ necks (P=.007) than in N0 necks and in the presence of other positive LNs (P=.01) than in the absence of other positive LNs. Of the 35 patients with pathologic LNs, the regional recurrence rate was significantly higher in cases with positive level IIb LNs (33% [4 of 12]) than without (4% [1 of 23]; P=.04). CONCLUSIONS: Level IIb LN pads may be preserved during elective neck dissection in the treatment of patients with clinically N0 necks with HPSCC. This area should be removed during therapeutic neck dissection in the treatment of clinically N+ necks.

Adult↗

CpG island methylation of genes accumulates during the adenoma progression step of the multistep pathogenesis of colorectal cancer.

Genetic alterations occur during the adenoma-carcinoma sequence of colon cancer formation and drive the initiation and progression of colon cancer formation. The aberrant methylation of genes is an alternate, epigenetic mechanism for silencing tumor suppressor genes in colon cancer. The aim of this study was to determine on a global and gene-specific level the role of CpG island methylation in the initiation and progression of colon cancer. Consequently, we assessed the frequency of gene methylation in tumors representative of the commonly recognized histological steps of the adenoma-carcinoma progression sequence through the analysis of eight genes previously identified to be methylated in colon cancer, MGMT, HLTF, MLH1, p14(ARF), CDKN2A, TIMP3, THBS1, and CDH1. We observed that the proportion of tumors carrying methylated alleles increased from adenomas to adenocarcinomas but that the proportion of tumors with methylated alleles was not different between adenocarcinomas and metastases (69% versus 90%, P = 0.01 and 90% versus 81%, P > 0.05). The most substantial difference occurred between early and advanced adenomas (47% versus 84%, P = 0.018). Furthermore, we observed that the frequency of gene methylation at the different steps of the progression sequence varied between genes. Thus, the aberrant methylation of genes appears to increase most significantly during the progression of early adenomas to advanced adenomas, and the frequency of specific gene methylation at the different steps of the adenoma-carcinoma progression sequence varies in a gene-specific fashion.

Adenocarcinoma↗

Bionectins A-C, epidithiodioxopiperazines with anti-MRSA activity, from Bionectra byssicola F120.

Three new epidithiodioxopiperazine compounds, bionectins A (1), B (2), and C (3), along with a known compound, verticillin D (4), have been isolated from the mycelium of liquid fermentation cultures of the fungus Bionectra byssicola F120. The structures of compounds 1-3 were assigned on the basis of MS and NMR data. Compounds 1 and 2 incorporate a dioxopiperazine moiety with a disulfide bridge in their molecules, while 3 contains a dioxopiperazine ring with two methylsulfanyl groups. Compounds 1 and 2 exhibited antibacterial activity against S. aureus including methicillin-resistant S. aureus (MRSA) and quinolone-resistant S. aureus (QRSA), with MIC values of 10-30 microg/mL, while 3 showed no antibacterial activity even at 100 microg/mL.

Anti-Bacterial Agents↗

Abdominal pain accompanied by weight loss may increase the diagnostic yield of capsule endoscopy: a Korean multicenter study.

OBJECTIVE: Capsule endoscopy (CE) is approved for the evaluation of obscure gastrointestinal (GI) bleeding and its use has increased in the assessment of patients with various small-bowel disorders. The yield of CE for indications of disorders other than GI bleeding is not yet well described. The aim of the present study was to determine in which subgroup of patients with unexplained abdominal pain, CE would be a helpful evaluation tool. MATERIAL AND METHODS: The results of CE in 110 patients (70 M, 40 F, mean age 50.8+/-14.1 years) with unexplained abdominal pain from 12 tertiary referral centers between September 2002 and September 2004 were retrospectively analyzed. RESULTS: The visualization of the small bowel to the cecum was successfully carried out in 69.1% of the patients. Nineteen out of the 110 cases revealed positive findings that explained the symptoms of the patient (diagnostic yield=17.3%). Diagnosis included small-bowel stricture (5), Crohn's disease (3), small-bowel tumor (2), radiation-induced enteritis (1), NSAID-induced enteropathy (1), ischemic ileitis (1), diffuse lymphangiectasia (1), and significant erosion or ulceration (5). By univariate logistic regression analysis, the positive findings of CE were significantly associated with weight loss (odds ratio (OR), 11.9; 95% CI [2.0, 70.6]), elevated erythrocyte sedimentation rate (ESR) (>20 mm/h) (OR, 11.5; 95% CI (1.9, 69.5)), elevated C-reactive protein (CRP) (>or=0.4 mg/dL) (OR, 5.0; 95% CI (1.6, 15.9)), and hypoalbuminemia (albumin<3 g/dL) (OR, 23.1; 95% CI (2.4, 223.1)). Using a multivariate analysis, weight loss was found to be a significant risk factor for positive findings of CE (OR, 18.6; 95% CI (1.6, 222.4), p=0.02). CONCLUSIONS: The results of this study suggest that CE can be helpful in patients suffering from abdominal pain that cannot be explained by established examinations, if the pain is accompanied by weight loss.

Abdominal Pain↗

Treatment of contralateral N0 neck in early squamous cell carcinoma of the oral tongue: elective neck dissection versus observation.

OBJECTIVES/HYPOTHESIS: Prophylactic treatment of contralateral N0 neck in early squamous cell carcinoma (SCC) of the oral tongue is a controversial issue. The aim of this study was to analyze the rates of occult metastases and their prognostic effects in stage I and stage II SCC of the oral tongue, and to compare the results of elective neck dissection to observation of the contralateral N0 neck in the treatment of these patients. STUDY DESIGN: Retrospective review. METHODS: We reviewed the medical records of 54 patients who were treated at Severance Hospital from 1992 to 2003 and had been diagnosed with stage I or stage II SCC of the oral tongue and had not received prior treatment. All patients underwent an ipsilateral elective neck dissection simultaneously with the primary lesion. The management of the contralateral N0 necks involved "watchful waiting" in 29 patients and elective neck dissection in 25 patients. Surgical treatment was followed by radiotherapy in 20 patients. Of these, seven patients belonged to the "observation" group who did not receive contralateral elective neck dissection. The follow-up period ranged from 3 to 110 months, with a mean of 56.3 months. Data were analyzed using the Kaplan-Meier method, the log-rank test, and the chi(2) test. RESULTS: Fifteen patients (28%, 15 of 54) had occult metastases. Of these, 14 patients (26%, 14 of 54) had ipsilateral pathologic metastases. The remaining case (4%, 1 of 25) had the only contralateral level II occult neck metastasis without ipsilateral metastasis. Disease recurred in 17 of 54 patients (31%). Of these, eight cases (47%, 8 of 17) had regional recurrences. All regional recurrences developed in the ipsilateral neck; there were no cases of contralateral neck recurrence. The 5-year actuarial disease-free survival rates were 82% for the "observation" group and 68% for the elective neck dissection group. This difference was not statistically significant (P = .182). The 5-year actuarial disease-free survival rates were 83% for the "observation" group when those patients who underwent radiotherapy were excluded (n = 22) and 68% for the elective supraomohyoid neck dissection group (n = 25), which showed no statistically significant difference (P = .127). CONCLUSIONS: This study showed that ipsilateral elective neck management is indicated for stage I and II SCC of the oral tongue. On the other hand, our series suggests that contralateral occult lymph node metastasis was unlikely in early-stage oral tongue SCC, and that there was no survival benefit for patients who underwent elective neck dissection in place of observation. Thus, it may not harmful to observe the contralateral N0 neck in the treatment of early oral tongue cancer.

Adult↗

Management of contralateral N0 neck in pyriform sinus carcinoma.

OBJECTIVE: The hypopharynx has a rich lymphatic network that places patients with tumors of the hypopharynx at high risk for early dissemination of the disease into the cervical lymphatics. Therefore, ipsilateral elective neck dissection of clinically N0 neck in lateralized lesions of hypopharyngeal squamous cell carcinomas (SCCs) is widely accepted as a standard treatment. However, the management of the contralateral N0 neck is still controversial. The aim of this study was to evaluate the incidence and predictive factors of contralateral occult lymph node metastasis in pyriform sinus SCC. MATERIALS AND METHODS: We performed a retrospective analysis of 43 patients with N0 to 3 pyriform sinus SCC with contralateral clinically node-negative necks who had also received contralateral elective neck dissections from 1994 to 2003. Surgical treatment was followed by postoperative radiotherapy in 41 patients. The follow-up period ranged from 4 to 135 months (mean, 40 months). The Kaplan-Meier method and log-rank test were used to calculate the disease-specific survival rates and prognostic significance of contralateral occult lymph node metastasis. RESULTS: Contralateral occult lymph node metastases occurred in 16% (seven of 43) of the subjects. Twenty-six percent of the 27 subjects with clinically node-positive ipsilateral neck developed contralateral occult lymph node metastases, whereas 0% of the 16 subjects with N0 ipsilateral necks (P=.035) developed the disease. Moreover, in cases with primary site extension across the midline, the rate of contralateral occult neck metastasis was significantly higher (P=.010). However, there were no statistically significant differences in age, sex, early versus advanced T stage, number of ipsilateral positive nodes, lymph nodes with extracapsular spread, primary subsite of medial versus lateral pyriform sinus, pyriform sinus apex involvement, and growth type. Patients with no evidence of contralateral nodal cancer had significantly improved disease-specific survival over patients with any pathologically positive nodes (5-year disease-specific survival rate, 66% vs. 33%, P<.05). CONCLUSION: The patients with pyriform sinus SCC with clinically ipsilateral N+ neck and/or extension across the midline are at greater risk for contralateral occult neck metastases. Furthermore, patients who present with a contralateral metastatic neck have a worse prognosis than those staged as N0. Therefore, we advocate bilateral neck treatment in patients with pyriform sinus SCC with clinically ipsilateral node metastases and/or extension across the midline.

Adult↗