Yaoh-Shiang Lin

Squamous cell carcinoma of the buccal mucosa: An aggressive cancer requiring multimodality treatment

In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment.

Epidemiology of Oral Cavity Cancer in Taiwan with Emphasis on the Role of Betel Nut Chewing

This article reports the epidemiological characteristics and the possible contributing etiology of oral cavity cancer in Taiwan. Data on oral cavity cancer from the period between 1986 and 1997 were compiled from the Taiwan Cancer Registry Annual Report. The amount of average annual consumption per person of cigarettes, alcohol and betel nut were extracted from the Annual Report of Taiwan Tobacco and Wine Monopoly Bureau and the Agriculture Counsel of Taiwan. The incidence of oral cavity cancer increased annually. Both the total and male incidence have increased substantially since 1993. Regarding the peak incidence, most cases were seen in the sixth to eighth decades of life. Multiple regression models indicated that 86.2% variation in the incidence of oral cavity cancer was explained by the annual average betel nut consumption per person. These results imply that those who chew betel nut belong to a high-risk group and require special consideration and attention regarding health education and health promotion.

Quercetin Suppresses Drug-Resistant Spheres via the p38 MAPK–Hsp27 Apoptotic Pathway in Oral Cancer Cells

Background Treatment failure in oral squamous cell carcinoma (OSCC) leading to local recurrence(s) and metastases is mainly due to drug resistance. Cancer stem cells (CSCs) are thought be responsible for the development of drug resistance. However, the correlations between CSCs, drug resistance, and new strategy against drug resistance in OSCC remain elusive. Methods A drug-resistant sphere (DRSP) model was generated by using a nonadhesive culture system to induce drug-resistant cells from SCC25 oral cancer cells. A comparative analysis was performed between the parent control cells and DRSPs with a related treatment strategy focusing on the expression of epithelial–mesenchymal transition (EMT)-associated markers, drug-resistance-related genes, and CSC properties in vitro, as well as tumorigenicity and the regimen for tumor regression in vivo. Results Our data show the presence of a phenomenon of EMT with gradual cellular transition from an epithelioid to mesenchymal-like spheroid morphology during induction of drug resistance. The characterization of DRSPs revealed the upregulation of the drug-resistance-related genes ABCG2 and MDR-1 and of CSC-representative markers, suggesting that DRSPs have greater resistance to cisplatin (Cis) and stronger CSC properties compared with the control. Moreover, overexpression of phosphorylated heat-shock protein 27 (p-Hsp27) via the activation of p38 MAPK signaling was observed in DRSPs. Knockdown of Hsp27 decreased Cis resistance and induced apoptosis in DRSPs. Furthermore, an inhibitor of Hsp27, quercetin (Qu), suppressed p-Hsp27 expression, with alterations of the EMT signature, leading to the promotion of apoptosis in DRSPs. A xenographic study also confirmed the increase of tumorigenicity in DRSPs. The combination of Qu and Cis can reduce tumor growth and decrease drug resistance in OSCC. Conclusions The p38 MAPK–Hsp27 axis plays an important role in CSCs-mediated drug resistance in OSCC. Targeting this axis using Qu combined with Cis may be a treatment strategy to improve prognosis in patients with OSCC.

Etiology of Vocal Cord Paralysis

Objective: Vocal cord paralysis (VCP) is a sign of a certain underlying disease, a diagnosis which can be attributed to various causes. This study intends to analyze the contemporary etiology of VCP in a tertiary medical center. Materials and Methods: A retrospective review of medical records from June 2000 to December 2004 of hospitalized patients with VCP was done to determine the etiology. Results: Two hundred and ninety-one patients with a determined etiology were identified, consisting of 176 males and 115 females. Unilateral VCP was present in 259 patients, while 32 presented with bilateral VCP. The causes were surgical in 40.2%, neoplastic in 29.9%, idiopathic in 10.7%, traumatic in 8%, central in 3.8%, radiation-induced in 3.4%, inflammatory in 2%, cardiovascular in 1.7% and other causes in 0.3% of the cases. Thyroidectomy represented the most common surgery for VCP and was the cause in 57 patients. Lung cancer was responsible for 34 cases and was the most common neoplastic etiology. In males, neoplasm was the most common cause occurring in 63 of 176 males, whereas surgery was most frequent in 59 of 115 females. Conclusion: Surgical trauma, mainly thyroidectomy, is the most common cause of VCP in hospitalized patients. The possibility of a neoplasm must be ruled out before VCP is labeled idiopathic. A benign thyroid tumor could also cause VCP. Besides, radiation-induced cranial nerve paralysis in head and neck cancer may play a significant role.

DOSE ESCALATION USING TWICE-DAILY RADIOTHERAPY FOR NASOPHARYNGEAL CARCINOMA: DOES HEAVIER DOSING RESULT IN A HAPPIER ENDING?

PURPOSE To present our experience using a twice-daily radiotherapy (RT) technique, including hyperfractionated and accelerated-hyperfractionated RT, on nasopharyngeal carcinoma (NPC) patients. The dose to the primary tumor was increased in the hope that local control could be increased without the cost of increased late complications. We analyzed acute and late complications and local control and compared the results with the results of NPC patients treated during the same period using conventional once-daily RT. METHODS AND MATERIALS Between October 1991 and July 1998, 222 histologically confirmed, Stage M0, previously unirradiated NPC patients completed RT at our hospital. Most patients had American Joint Committee on Cancer (AJCC) 1992 Stage III and IV disease. Among them, 88 received altered fractionated, twice-daily RT; 76 patients received hyperfractionated RT and 12 accelerated-hyperfractionated RT. The remaining 134 patients received a conventional once-daily regimen. Hyperfractionated RT was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. For the accelerated-hyperfractionated patients, 160 cGy b.i.d. was given, also at 6-h intervals. The median dose in the twice-daily group was 7810 cGy (range 6840-8200). In the once-daily regimen, RT was delivered using 180-200 cGy q.d. The median tumor dose to the primary tumor was 7000 cGy (range 6560-8100) given during about 8 weeks. The median follow-up time was 70.5 and 72 months for the twice-daily and once-daily groups, respectively. RESULTS The incidence of acute toxicities was higher in the twice-daily group with more severe mucositis and moist desquamation than in the once-daily group. Both groups had a similar incidence of late complications, except for 3 cases of temporal lobe necrosis in the twice-daily group, all in patients treated with 160 cGy. No difference was noted in recurrence-free local control between the two groups when the individual T stage was compared using AJCC 1992 or 1997 criteria (p = 0.51 and 0.59, respectively). The 5-year local control rate for T1-3 (AJCC 1997) was 93.2% for the twice-daily group and 86.4% for the once-daily group (p = 0.45). In Stage T4 (AJCC 1997) patients, the local control rate dropped drastically to 43.5% and 36.9% for the twice-daily and once-daily groups, respectively. The overall neck control rate at 5 years was 87.3% and 80.3% for the twice-daily and once-daily patients, respectively (p = 0.16). The overall locoregional control rate was 82.7% for the twice-daily group and 66.6% for the once-daily group. The difference was again not statistically significant, but showed a tendency in favor of the twice-daily regimen (p = 0.055). Locoregional failure occurred mainly in Stage T4 patients with central nervous invasion for whom local control was particularly poor, with a failure rate of about 60%. CONCLUSION The present data suggest that NPC patients can be safely treated using a 120-cGy twice-daily program with a 6-h interval up to 8000 cGy. The accelerated-hyperfractionated technique is not recommended. A large discrepancy in local control between patients with T1-3 and T4 disease was noted. For T1-3 disease, an excellent local control rate >90% was achieved using the twice-daily regimen. In contrast, failure in the T4 patients was as high as 55% in the twice-daily group and reached 65% in the once-daily group. More rigorous treatment is needed using either additional dose escalation or other strategies for T4 NPC patients. With a dose escalation of 1000 cGy using 120-cGy twice-daily RT, a trend toward better locoregional control and disease-specific survival was noted in the twice-daily group. Whether this difference was truly the result of an increased dose needs additional confirmation in studies with larger patient numbers.

Middle turbinate osteoma presenting with ipsilateral facial pain, epiphora, and nasal obstruction

Nasal osteomas are benign tumors of the bone of the nose and paranasal sinus that are capable of extending to surrounding structures, which may result in severe complications such as orbital involvement or intracranial invasion. They most commonly occur in the frontal sinus, followed by the ethmoidal and maxillary sinuses. Occurrence in the sphenoidal sinus is very rare.1 It is also rare that an osteoma occurs in the nasal cavity. An extensive literature search revealed only one case, reported by Whittet and Quiney2 in 1988. In the current report, we present the case of a patient with middle turbinate osteoma accompanied by ipsilateral facial pain, epiphora, and nasal obstruction.

Characterization of 4-[ 18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: A dynamic study

INTRODUCTION Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-[(18)F]-ADAM), in nonhuman primate brain using positron emission tomography (PET). METHODS Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[(18)F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[(18)F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[(18)F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated. RESULTS The distribution of 4-[(18)F]-ADAM reached equilibrium 120-150 min after injection. The mean SURs were 2.49 ± 0.13 in MB, 1.59 ± 0.17 in TH, 1.35 ± 0.06 in ST and 0.34 ± 0.03 in FC, and the minimum variability was shown 120-150 min after 4-[(18)F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75-2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[(18)F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls. CONCLUSION 4-[(18)F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain.

Reappraisal of the anticancer efficacy of quercetin in oral cancer cells

Background: Despite increased experience in therapy, the overall outcome of oral squamous cell carcinoma (OSCC) has not improved because of the relative resistance to chemotherapeutic drugs in addition to local invasion and frequent regional lymph node metastases. Quercetin (Qu) is a principal flavonoid compound and an excellent free‐radical‐scavenging antioxidant that promotes apoptosis. Limited reports regarding the molecular or cellular role of Qu in anticancer properties on OSCC have been presented. This study was conducted to clarify the efficacy of Qu on OSCC in vitro and further to evaluate the possible mechanism(s). Methods: Cultured OSCC cells (SCC‐25) and human gingival fibroblasts (HGFs) were treated with different concentrations of Qu. Cell viability and cell colony‐forming potential were detected with the MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide) and colony growth assays. Cell‐cycle analysis and apoptosis were measured by flow cytometry. Cell migration and invasion were tested using the micropore chamber assay. Results: Cell viability and colony‐forming potential were decreased in a dose‐dependent manner following Qu treatment. Qu also dose‐dependently inhibited the proliferation of SCC‐25 cells via both G1 phase cell cycle arrest and mitochondria‐mediated apoptosis. In addition, Qu also decreased the abilities of migration and invasion of SCC‐25 cells in a dose‐dependent manner. Conclusion: Qu effectively inhibits cell growth and invasion/migration of SCC‐25 cells in vitro. The cellular and molecular mechanisms are via cell cycle arrest accompanied by mitochondria‐mediated apoptosis. Our findings suggest that Qu may have potential as a new chemopreventive agent or serve as a therapeutic adjuvant for OSCC.

Resveratrol regulates N-methyl-D-aspartate receptor expression and suppresses neuroinflammation in morphine-tolerant rats.

BACKGROUND:In the present study, we examined the effects and mechanisms of the Chinese herb resveratrol on attenuation of morphine tolerance in rats. METHODS:Male Wistar rats were implanted with 2 intrathecal catheters; one catheter was connected to a mini-osmotic pump, used for either morphine (15 &mgr;g/h) or saline (1 &mgr;L/h) infusion for 5 days. On day 5, resveratrol (7.5, 15, 30, or 60 &mgr;g), dimethyl sulfoxide (5 &mgr;L), or saline (5 &mgr;L) was injected via the other catheter immediately after the discontinued morphine infusion. Three hours later, intrathecal morphine (15 &mgr;g in 5 &mgr;L saline) was given. All rats received the nociceptive tail-flick test every 30 minutes for 120 minutes after the morphine challenge. RESULTS:Long-term morphine infusion induced antinociceptive tolerance and up-regulated N-methyl-D-aspartate receptor (NMDAR) subunit NR1 and NR2B expression in the synaptosome fraction of the tolerant spinal cord dorsal horn. Resveratrol pretreatment provided a significant antinociceptive effect of morphine in morphine-tolerant rats, and it was associated with reversal of the up-regulated NR1 and NR2B subunits in the synaptosome fraction of morphine-tolerant rat spinal cords. NR1/NR2B-specific antagonist ifenprodil treatment produced a similar effect as that of resveratrol. Furthermore, an increase of postsynaptic density-95/NR1/NR2B complex immunoprecipitation in morphine-tolerant rat spinal cord was also inhibited by resveratrol pretreatment. Moreover, chronic morphine infusion activated glial cells with an increase of proinflammatory cytokine tumor necrosis factor-&agr;, interleukin-1&bgr;, and interleukin-6 mRNA expression in morphine-tolerant rat spinal cords and these effects were suppressed by resveratrol pretreatment before the morphine challenge. CONCLUSIONS:Resveratrol attenuates morphine tolerance by inhibiting neuroinflammation and down-regulating NMDAR NR1 and NR2B subunit expression. Resveratrol regulates the NMDAR expression, which might be involved in a loss of scaffolding postsynaptic density-95 protein.

Medial sural artery perforator flap for tongue and floor of mouth reconstruction.

The radial forearm flap is frequently considered the first choice for tongue reconstruction, but the disadvantages of donor site morbidity are well known. The search for another thin skin flap as an alternative has led to the application of the medial sural artery perforator flap.