Chun-Ta Liao

Chang Gung Memorial Hospital, T’ai-pei, Taipei, Taiwan

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Publications (189)746.11 Total impact

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    ABSTRACT: Background: The osteoseptocutaneous fibula flap has been widely used for bone and soft tissue reconstruction from its first description in 1975. Nowadays, this flap has become the workhorse flap for head and neck reconstruction because of its suitability for mandible reconstruction. However, the reliability of the skin paddle is still controversial. We described a modified method for the harvesting of an osteoseptocutaneous flap to obtain a more reliable skin paddle while minimizing the donor site morbidity. Methods: One hundred fifty-one consecutive patients were enrolled in the current study from January 2005 to December 2013. All of them underwent a free osteoseptocutaneous flaps for either head and neck (n = 135) or extremity (n = 16) reconstruction following the posterior approach harvest technique. Demographics data of all the patients were collected: age, sex, defect location, and etiology. The variables included for the statistical analysis were: size of the skin paddle, time of harvesting, reoperation, split skin paddle, and single or double barrel fashion for the inset. The outcomes measured were the flap success rate and the skin paddle survival. Results: The flap success rate was 97.3%. The mean harvesting time was 45 minutes. The mean width and length of the skin paddle was 7.1 ± 2.6 and 17.41 ± 4.4 cm, respectively. The reexploration rate was 18.5%, and the salvage was achieved 85.7% of the cases. Partial skin paddle necrosis was found in 13.2% of the cases. The fact of having a reexploration in the postoperative period was the only variable significantly associated with the skin paddle necrosis (P = .001). Conclusions: According to our experience, the posterior approach for the harvest of the osteoseptocutaneous fibula flap is a safe technique and offers many advantages, such as a better visualization of the perforators, beneficial for chimeric flap elevation, preservation of the muscular fascia in the donor site, and an earlier diagnosis of any anatomical variation. Both the reliable and the versatility of the skin paddle can substantially improve with this approach.
    Annals of plastic surgery 11/2015; DOI:10.1097/SAP.0000000000000638 · 1.49 Impact Factor
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    ABSTRACT: Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme. A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures. Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001). OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis.
    PLoS ONE 09/2015; 10(9):e0136918. DOI:10.1371/journal.pone.0136918 · 3.23 Impact Factor
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    ABSTRACT: CYFRA 21-1 (cytokeratin 19 fragment) and C-reactive proteins (CRP) were separately reported to be associated with prognosis of head and neck squamous cell carcinoma. The combined roles of CYFRA 21-1 and CRP levels were rarely investigated in oral squamous cell carcinoma (OSCC). The purpose of the present study was to analyze the relationship between preoperative levels of both CYFRA 21-1 and CRP, with clinicopathological factors and prognosis in OSCC patients. A retrospective study was performed on 130 OSCC patients between December 2010 and June 2013. Their serum CYFRA 21-1 and CRP levels were measured preoperatively. CYFRA 21-1 level of ≥3.3 ng/mL and CRP level of ≥5.0 mg/L were significantly associated with pathological tumor status (P < 0.001), tumor depth (>10 vs. ≤10 mm, P = 0.001), bone invasion (P = 0.001), skin invasion (P = 0.006), pathologic nodal metastasis (P = 0.012), and disease-free survival (P = 0.009). Higher CYPFRA 21-1 and CRP levels were also associated with higher risks of distant metastasis (log-rank test, P = 0.013, (HR [95 % CI]) 1.692 [1.097-2.414]). Preoperative CYFRA 21-1 and CRP levels are probable candidates as biomarkers for risk stratification in OSCC.
    World Journal of Surgical Oncology 08/2015; 13(1):253. DOI:10.1186/s12957-015-0656-9 · 1.41 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):3855-3855. DOI:10.1158/1538-7445.AM2015-3855 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):3868-3868. DOI:10.1158/1538-7445.AM2015-3868 · 9.33 Impact Factor
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    ABSTRACT: The Ang's risk profile (based on p16, smoking, and cancer stage) is a well-known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). We sought to investigate whether heterogeneity in (18) F-fluorodeoxyglucose (FDG) PET images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced-stage OPSCC. Patients with stage III-IV OPSCC who completed primary therapy were eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease-specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)-based model was constructed. A total of 113 patients were included, of which 28 were p16-positive. Multivariate analysis identified the Ang's profile, EGFR, and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16-positive and -negative cases. The c-statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. We conclude that our novel index may improve the prognostic stratification of patients with advanced-stage OPSCC. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 08/2015; DOI:10.1002/ijc.29811 · 5.09 Impact Factor
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    ABSTRACT: Ultra-deep targeted sequencing (UDT-Seq) has advanced our knowledge on the incidence and functional significance of somatic mutations. However, the utility of UDT-Seq in detecting copy number alterations (CNAs) remains unclear. With the goal of improving molecular prognostication and identifying new therapeutic targets, we designed this study to assess whether UDT-Seq may be useful for detecting CNA in oral cavity squamous cell carcinoma (OSCC). We sequenced a panel of clinically actionable cancer mutations in 310 formalin-fixed paraffin-embedded OSCC specimens. A linear model was developed to overcome uneven coverage across target regions and multiple samples. The 5-year rates of secondary primary tumors, local recurrence, neck recurrence, distant metastases, and survival served as the outcome measures. We confirmed the prognostic significance of the CNA signatures in an independent sample of 105 primary OSCC specimens. The CNA burden across 10 targeted genes was found to predict prognosis in two independent cohorts. FGFR1 and PIK3CAamplifications were associated with prognosis independent of clinical risk factors. Genes exhibiting CNA were clustered in the proteoglycan metabolism, the FOXO signaling, and the PI3K-AKT signaling pathways, for which targeted drugs are already available or currently under development. UDT-Seq is clinically useful to identify CNA, which significantly improve the prognostic information provided by traditional clinicopathological risk factors in OSCC patients.
    Oncotarget 06/2015; 6(23). DOI:10.18632/oncotarget.4336 · 6.36 Impact Factor
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    ABSTRACT: Complications arising from anastomotic failure may occur after pharyngoesophageal reconstruction. In this report we present results of pharyngoesophageal reconstruction with free thigh flaps using a refined design and inset strategy in a series of patients. From May 2011 to December 2012, pharyngoesophageal oncologic defects were reconstructed in 12 men using thigh flaps. Flaps were designed to exceed defect circumference to allow draping of the excess over injury-prone vessels (so-called delta-inset). Patients were 39- to 68-years-old (mean, 51.8-years-old) at the time of surgery. BMI ranged from 17 to 28 kg/m(2) (average, 21.5 kg/m(2) ). The sites of defects were the hypopharynx in 11 cases and the pharynx in 1 case. Ten anterolateral thigh (ALT) flaps and 2 anteromedial thigh (AMT) flaps were used. All patients underwent radiation therapy. The average flap size was 22 × 9 cm (range: 16-26 × 7-11 cm(2) ). There were no partial or total flap losses, and no donor site complications. Follow-up was 19.3 months (range: 2.4-21.6 months) including 8 patients (75%) who succumbed to disease in the follow-up period. Oral intake was achieved in all patients. Recipient site complications occurred in 50% of cases and included fistula (2 cases), fistula and stricture (2 cases), stricture (1 case), and lymphocele (1 case). Four patients required revision for fistula. A refined thigh flap design and inset method in pharyngoesophageal reconstruction may circumvent complications arising from toxic drainage and vascular injury. However, there are insufficient data to make meaningful comparisons to alternative methods. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015. © 2015 Wiley Periodicals, Inc.
    Microsurgery 06/2015; DOI:10.1002/micr.22432 · 2.42 Impact Factor
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    ABSTRACT: : It is not uncommon that after using a fibular flap for lower gum cancer reconstruction, nonunion, chronic osteomyelitis, or fibular bone exposure occurs, which requires a composite bone and soft tissue reconstruction. Radial forearm osteocutaneous flap possesses the risk of stress fracture. Ulnar forearm osteocutaneous flap can be another option for small bone defect reconstruction. Six patients who had undergone fibular flap for mandible reconstructions and sustained either bone exposure (3 patients), chronic osteomyelitis (1 patient), malocclusion (1 patient), or osteoradionecrosis (1 patient) underwent ulnar forearm osteocutaneous flap with 3-cm ulnar bone for touch-up procedure. The distal radioulnar joints were fused with a screw. Six ulnar forearm osteocutaneous flap dissections were also performed on 4 fresh frozen cadavers to clarify the anatomic distribution of the distal ulnar artery. All 6 ulnar forearm osteocutaneous flaps survived with one re-exploration for venous occlusion. All presented bone union. Comparable to the clinical dissection, the cadaveric distal ulnar artery demonstrates a periosteal branch that runs between the proper ulnar nerve and dorsal sensory nerve. This periosteal branch comes out of an ulnar artery approximately 3 cm proximal to the wrist joint. Ulnar forearm osteocutaneous flap can provide a secondary flap of wide skin paddle and small segment bone for specific mandibular defect after a fibular flap transfer.
    Annals of plastic surgery 05/2015; 74 Suppl 2:S152-7. DOI:10.1097/SAP.0000000000000467 · 1.49 Impact Factor
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    ABSTRACT: Patients with advanced oral squamous cell carcinoma (OSCC) have heterogeneous outcomes that limit the implementation of tailored treatment options. Genetic markers for improved prognostic stratification are eagerly awaited. Herein, next-generation sequencing (NGS) was performed in 345 formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC patients. Genetic mutations on the hotspot regions of 45 cancer-related genes were detected using an ultra-deep (>1000×) sequencing approach. Kaplan-Meier plots and Cox regression analyses were used to investigate the associations between the mutation status and disease-free survival (DFS). We identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA, CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14 genes were found to predict DFS. A mutation-based signature affecting ten genes (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was devised to predict DFS. Two different resampling methods were used to validate the prognostic value of the identified gene signature. Multivariate analysis demonstrated that presence of a mutated gene signature was an independent predictor of poorer DFS (P = 0.005). Genetic variants identified by NGS technology in FFPE samples are clinically useful to predict prognosis in advanced OSCC patients.
    Oncotarget 04/2015; 6(20). DOI:10.18632/oncotarget.3768 · 6.36 Impact Factor
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    ABSTRACT: Head and neck cancer (HNC) is a prevalent cancer worldwide; however, clinically useful tumor markers for HNC have not been identified. Here, we aimed to identify secretory proteins from the tumor microenvironment as candidate circulating tumor markers. Samples derived from seven pairs of tumor interstitial fluid (TIF) and normal interstitial fluid (NIF) samples from patients with HNC were analyzed. The proteomes were determined by gel-based-mass-spectrometry proteomic methods. The most up-regulated protein, fascin was confirmed in the cancer tissues and cell culture supernatant by immunoblotting and immunohistochemistry assays. Serum fascin was determined in 40 HNC and 40 normal individuals by ELISA. After proteomics analysis, 189 peptides were identified, corresponding to 75 proteins. Of the 21 proteins which were identified more than twice, five up-regulated proteins identified most frequently including fascin. The most elevated fascin was over-expressed in cancer tissues and cell culture supernatant. Serum fascin was significantly up-regulated in the cancer patients (p<0.001) and correlated with pathological lymph node metastasis (p=0.022). To assess the diagnostic efficacy, serum levels of fascin and another potential biomarker SCCA were determined. Fascin showed a high predictable value with an area under the curve (AUC) of 0.808 (95% CI 0.723-0.901) in the receiver operator curve (ROC), compared to 0.501 (95% CI 0.378-0.634) for SCCA. We have identified 75 potential circulating tumor markers associated with HNC, including fascin. Serum fascin could discriminate cancer patients from healthy individuals; thus, it may serve as a circulating biomarker for HNC.
    Clinical Chemistry and Laboratory Medicine 03/2015; DOI:10.1515/cclm-2014-1016 · 2.71 Impact Factor
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    ABSTRACT: The clinical usefulness of pretreatment imaging techniques for predicting neck control in patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) treated with chemoradiation remains unclear. In this prospective study, we investigated the role of pretreatment dynamic contrast-enhanced perfusion MR imaging (DCE-PWI), diffusion-weighted MR imaging (DWI), and [18F]fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT derived imaging markers for the prediction of neck control in OHSCC patients treated with chemoradiation. Patients with untreated OHSCC scheduled for chemoradiation between August, 2010 and July, 2012 were eligible for the study. Clinical variables and the following imaging parameters of metastatic neck lymph nodes were examined in relation to neck control: transfer constant, volume of blood plasma, and volume of extracellular extravascular space (Ve) on DCE-PWI; apparent diffusion coefficient (ADC) on DWI; maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis on 18F-FDG PET/CT. There were 69 patients (37 with oropharynx SCC and 32 with hypopharynx SCC) with successful pretreatment DCE-PWI and DWI available for analysis. After a median follow-up of 31 months, 25 (36.2%) participants had neck failure. Multivariate analysis identified hemoglobin level <14.3 g/dL (P = 0.019), Ve <0.23 (P = 0.040), and ADC >1.14×10-3 mm2/s (P = 0.003) as independent prognostic factors for 3-year neck control. A prognostic scoring system was formulated by summing up the three significant predictors of neck control. Patients with scores of 2-3 had significantly poorer neck control and overall survival rates than patients with scores of 0-1. We conclude that hemoglobin levels, Ve, and ADC are independent pretreatment prognostic factors for neck control in OHSCC treated with chemoradiation. Their combination may identify a subgroup of patients at high risk of developing neck failure.
    PLoS ONE 12/2014; 9(12):e115933. DOI:10.1371/journal.pone.0115933 · 3.23 Impact Factor
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    ABSTRACT: The aim of this single-center study was to investigate whether performing an additional PET/CT scan before adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) can meaningfully improve disease-free (DFS) and disease-specific (DSS) 2-year survival rates. A total of 674 patients with oral cavity squamous cell carcinoma (OSCC) who received adjuvant therapy after radical surgery were included. Of them, 152 subjects were initially scheduled to receive an additional pre-RT/CCRT PET/CT scan within one week of starting adjuvant therapy. However, 16 patients were excluded due to either medical problems or refusal. Therefore, 136 subjects underwent a pre-RT/CCRT PET/CT scan (PET group), whereas 522 did not (NO PET group). All of the participants were followed-up for at least two years or censored at the last follow-up. The impact of pre-RT/CCRT PET/CT imaging was examined using Kaplan-Meier curves and Cox proportional hazard models. Two-year DFS (80% vs. 70%, P = 0.033) and DSS (84% vs. 75%, P = 0.010) rates were significantly higher in the PET than in the NO PET group. In the PET group, both DFS and DSS were higher in subjects with negative findings than in those without (88% vs. 22%, 91% vs. 36%, both P < 0.001). A prognostic scoring system based on the presence of the two independent risk factors in PET group (extracapsular spread and lymphatic invasion) predicted both DFS (P = 0.001, P < 0.001) and DSS (P = 0.001, P < 0.001). Nineteen patients (14%) had their treatment modified by pre-RT/CCRT PET/CT findings. Of them, 15 were treated with curative intent due to the presence of locoregional disease, whereas four received palliative care due to distant metastases. Seven of these patients are currently alive without disease. An additional pre-RT/CCRT PET/CT scan improves both DFS and DSS in patients with advanced OSCC. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 12/2014; 56(1). DOI:10.2967/jnumed.114.145300 · 6.16 Impact Factor
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    ABSTRACT: Purpose: The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. Methods: We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Results: Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. Conclusion: ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.
    European journal of nuclear medicine and molecular imaging 10/2014; 42(3). DOI:10.1007/s00259-014-2933-1 · 5.38 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):4146-4146. DOI:10.1158/1538-7445.AM2014-4146 · 9.33 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):3412-3412. DOI:10.1158/1538-7445.AM2014-3412 · 9.33 Impact Factor
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    ABSTRACT: Background Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients. Objectives This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment. Study design: Viral loads of E7 oncogenes for HPV 16/18 were measured by quantitative PCR tests in paraffin-embedded lesional specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable Cox regression analysis was used to identify the independent prognostic factors for 5-year DM and C statistics were further computed. Results By multivariable analysis, high HPV 16 E7 viral load (≥15.0 copies/genome); high HPV 18 E7 viral load (≥15.0 copies/genome); pathological N2 status (pN2); tumor depth ≥11 mm; extracapsular spread (ECS); and level IV/V metastases were independent risk factors for DM. We further identified three prognostic groups. In the high-risk group (level IV/V metastases or high HPV 16/18 E7 viral load plus pN2, tumor depth ≥11 mm, or ECS), the 5-year distant metastasis rate was 74%. In the intermediate-risk group (high HPV 16/18 E7 viral load, pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 17%. Finally, the 5-year DM rate was 1% in the low-risk group (no risk factors). The value of the C statistics was 0.78. Conclusions Among OSCC patients, high HPV 16/18 E7 viral load identifies a small subgroup of patients at high-risk of 5-year DM and suggest the need for more intensive treatments and follow-up strategies.
    Journal of Clinical Virology 10/2014; 61(2). DOI:10.1016/j.jcv.2014.07.007 · 3.02 Impact Factor
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    ABSTRACT: MicroRNA-196 (miR-196), which is highly up-regulated in oral cancer cells, has been reported to be aberrantly expressed in several cancers; however, the significance of miR-196 in oral cancer has not yet been addressed. Cellular functions in response to miR-196 modulation were examined, including cell growth, migration, invasion and radio/chemosensitivity. Algorithm-based studies were used to identify the regulatory target of miR-196. The miR-196 target gene and downstream molecular mechanisms were confirmed by RT-qPCR, western blot, luciferase reporter and confocal microscopy analyses. miR-196 expression was determined in paired cancer and adjacent normal tissues from oral cancer patients. Both miR-196a and miR-196b were highly over-expressed in the cancer tissue and correlated with lymph node metastasis (P = 0.001 and P = 0.006, respectively). Functionally, miR-196 actively promoted cell migration and invasion without affecting cell growth. Mechanistically, miR-196 performed it's their function by inhibiting NME4 expression and further activating p-JNK, suppressing TIMP1, and augmenting MMP1/9. miR-196 contributes to oral cancer by promoting cell migration and invasion. Clinically, miR-196a/b was significantly over-expressed in the cancer tissues and correlated with lymph node metastasis. Thus, our findings provide new knowledge of the underlying mechanism of cancer metastasis. miR-196 may serve as a promising marker for better oral cancer management.
    Molecular Cancer 09/2014; 13(1):218. DOI:10.1186/1476-4598-13-218 · 4.26 Impact Factor
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    ABSTRACT: Importance The current American Joint Committee on Cancer (AJCC) staging system for oral cancer demonstrates wide prognostic variability within each primary tumor stage and provides suboptimal staging and prognostic information for some patients.Objective To determine if a modified staging system for oral cancer that integrates depth of invasion (DOI) into the T categories improves prognostic performance compared with the current AJCC T staging.Design, Setting, and Participants Retrospective analysis of 3149 patients with oral squamous cell carcinoma treated with curative intent at 11 comprehensive cancer centers worldwide between 1990 and 2011 with surgery ± adjuvant therapy, with a median follow-up of 40 months.Main Outcomes and Measures We assessed the impact of DOI on disease-specific and overall survival in multivariable Cox proportional hazard models and investigated for institutional heterogeneity using 2-stage random effects meta-analyses. Candidate staging systems were developed after identification of optimal DOI cutpoints within each AJCC T category using the Akaike information criterion (AIC) and likelihood ratio tests. Staging systems were evaluated using the Harrel concordance index (C-index), AIC, and visual inspection for stratification into distinct prognostic categories, with internal validation using bootstrapping techniques.Results The mean and median DOI were 12.9 mm and 10.0 mm, respectively. On multivariable analysis, DOI was a significantly associated with disease-specific survival (P < .001), demonstrated no institutional prognostic heterogeneity (I2 = 6.3%; P = .38), and resulted in improved model fit compared with T category alone (lower AIC, P < .001). Optimal cutpoints of 5 mm in T1 and 10 mm in T2-4 category disease were used to develop a modified T staging system that was preferred to the AJCC system on the basis of lower AIC, visual inspection of Kaplan-Meier curves, and significant improvement in bootstrapped C-index.Conclusions and Relevance We propose an improved oral cancer T staging system based on incorporation of DOI that should be considered in future versions of the AJCC staging system after external validation.
    JAMA Otolaryngology - Head and Neck Surgery 07/2014; 140(12). DOI:10.1001/jamaoto.2014.1548 · 1.79 Impact Factor
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    ABSTRACT: Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have been successfully used to stratify risk groups in primary oral squamous cell carcinoma (OSCC) patients; however, related biomarkers have rarely been investigated in recurrent OSCC. The purpose of the present study was to analyze the relationships of SCC-Ag and CRP levels at the time of recurrence with clinical factors and prognosis. We retrospectively recruited patients with recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease-free, and at the time of recurrence. The SCC-Ag levels were significantly lowered after treatment (paired t-test: p = 0.001) and re-elevated at the time of recurrence (paired t-test: p = 0.027). An SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L at the time of recurrence were significantly associated with recurrent tumor status (P<0.001), recurrent nodal metastasis (χ2 trend test: P = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover, the influence of both elevated SCC-Ag and CRP levels on overall survival (P<0.001, H.R. [95% CI]: 5.406 [2.210-13.222]) still existed after adjusting for the recurrent tumor stage and patient age. The present study demonstrates that concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant metastasis, and survival after the diagnosis of recurrence. This study expands the applicability of these two markers in the risk stratification in recurrent OSCC.
    PLoS ONE 07/2014; 9(7):e103265. DOI:10.1371/journal.pone.0103265 · 3.23 Impact Factor

Publication Stats

3k Citations
746.11 Total Impact Points


  • 2001-2015
    • Chang Gung Memorial Hospital
      • • Department of Otorhinolaryngology
      • • Division of Radiation Oncology
      T’ai-pei, Taipei, Taiwan
  • 2014
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2003-2014
    • Chang Gung University
      • • School of Medicine
      • • College of Medicine
      • • Department of Otolaryngology
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2006
    • Xiamen Chang Gung Hospital
      Amoy, Fujian, China