Zhigang Huang

Genetic polymorphisms in cytochrome P450 genes are associated with an increased risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population.

The purpose of this study was to examine whether functional polymorphisms in the cytochrome P450 (CYP) enzyme genes affect the risk of developing larynx and hypopharynx squamous cell carcinoma (SCC). We investigated CYP1A1, CYP1B1, CYP2E1, and CYP3A4 polymorphisms in 278 patients with laryngeal and hypopharyngeal SCC and 278 control subjects by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with the CYP1A1 3798CC or TC genotype had an odds ratio (OR) of 3.26 (95% confidence interval CI=1.76-6.03) or 1.56 (95% CI=1.06-2.31), compared with those with the TT genotype. An increased risk was also associated with the CYP1A1 462Val/Val genotype (OR=2.39, 95% CI=1.11-5.16), compared with the TT genotype. Haplotype analysis suggested a synergistic effect of these two polymorphisms. A multiplicative joint effect between the CYP1A1 3798T>C polymorphism and smoking was observed. The OR (95% CI) of the TC or CC genotype for nonsmokers and smokers of >20 pack-years were 1.85 (0.99-3.44) or 8.15 (4.35-15.26), respectively (P(trend)<0.05). The CYP1A1 single-nucleotide polymorphisms are associated with an increased risk of developing smoking-related laryngeal and hypopharyngeal SCC in a Han Chinese population.

Rhinoscleroma: A retrospective study of pathologic and clinical features

OBJECTIVE Rhinoscleroma, a chronic granulomatous bacterial disease of the nasal mucosa that often extends through the lower respiratory tract, is caused by infection with the gram-negative bacillus Klebsiella rhinoscleromatis (KR). We report the clinicopathology and histology associated with KR infection-induced rhinoscleroma in patients admitted to the Beijing Tongren Hospital over a 30-year period. METHODS The clinical and pathologic features of 40 cases of upper aerodigestive tract infections were retrospectively studied. Histochemical examination of biopsy samples was performed, including periodic acid-Schiff, modified Warthin-Starry, and acid-fast stains. In addition, immunohistochemical staining for CD43, CD20, CD68, and lysozymes was performed in 11 specimens, and 8 specimens were analyzed by transmission electron microscopy. RESULTS KR infection was confirmed in each of the 40 samples. Twenty-seven patients remained relapse free 1 to 10 years following treatment with antibiotic supplemented in some cases with surgery or radiotherapy, and all 13 cases of relapse were successfully eradicated by the end of treatment. KR infection was localized to phagosomes within Mikulicz cells, as determined by immunohistochemistry and electron microscopy. Significant tissue injury was observed in most cases. CONCLUSION Long-term antibiotic therapy successfully eradicated KR infection in all cases. Although late diagnosis was common in this cohort, retrospective examination of biopsy samples suggests that diagnosis can be improved by combining clinical findings with histologic analysis.

Salvage transoral laser microsurgery for early recurrent glottic carcinoma after primary laser treatment

Abstract Conclusion: Salvage transoral laser microsurgery (TLM) may be a curative organ-preserving treatment for early recurrent glottic carcinoma after primary laser resection. However, failure after TLM seems to be associated with decrease of survival and larynx preservation rates. Objective: To evaluate the oncological results of salvage TLM for early recurrent glottic carcinoma after primary laser treatment. Methods: Records of 50 patients with local recurrences of glottic carcinoma treated by salvage TLM between January 1994 and December 2008 were retrospectively analyzed. Results: Thirty-six rT1 and 14 rT2 lesions were treated with salvage TLM. Mean follow-up was 68.3 months. Thirty-one patients were cured by first salvage TLM and four by further laser procedures. The other 15 patients were finally salvaged by laryngectomy or radiotherapy. Five-year overall survival, disease-specific survival, local control, and loco-regional control rates were 89.9%, 97.9%, 62.3%, and 60.1%, respectively. Larynx preservation rate after long-term follow-up was 86%. In univariate analysis, second local recurrence showed a statistically significant impact on disease-specific survival rate ( p = 0.049) and larynx preservation rate ( p = 0.006). In multivariate analysis, it was associated with a statistically significant decrease in larynx preservation rate ( p = 0.016). There was no statistically significant difference in oncological results between patients with and without anterior commissure involvement.

The Proton-Sensing G-Protein Coupled Receptor GPR4 Promotes Angiogenesis in Head and Neck Cancer

Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor survival and is the sixth most common cancer worldwide. Gastroesophageal reflux is a common event in SCCHN patients. GPR4 is a proton-sensing G-protein coupled receptor, which can be activated by acidosis. The objective of this study was to explore the role of GPR4 in acid exposure and tumor angiogenesis in SCCHN. In this study, we confirmed that overexpressing GPR4 in SCCHN cells could increase the expression and secretion of IL6, IL8 and VEGFA at pH 5.9. This effect could be inhibited by SB203580 (a p38 inhibitor). Western blot analysis indicated that phosphorylation of p38 increased in GPR4 infected cells at pH 5.9, which could be inhibited by SB203580. In tube formation assay, HMEC-1 cells were incubated with conditioned medium (CM, pH 5.9, 6.5, 7.4) derived from control and GPR4 infected SCCHN cells. Tube length was significantly increased in HMEC-1 cells incubated with CM from GPR4 infected cells compared with control cells at pH5.9, which indicated the pro-angiogenic effect of GPR4 in acidic pH. The neutralizing antibodies of IL6, IL8 and VEGFA could inhibit tube formation of HMEC-1 cells. In vivo, the effect of GPR4 on angiogenesis was investigated with the chick chorioallantoic membrane (CAM) model. Control and GPR4 infected SCCHN cells were seeded onto the upper CAM surface (n = 5 in each group) and 5 μL DMEM/F12 (pH 5.9, 6.5, 7.4) was added to the surface of the cell every 24 h. Four days later, the upper CAM were harvested and the ratio of the vascular area to the CAM area was quantified using Image-Pro Plus 6.0 software. GPR4 infected cells could recruit more vascular than control cells at pH5.9. In conclusion, we suggested that GPR4 induces angiogenesis via GPR4-induced p38-mediated IL6, IL8 and VEGFA secretion at acidic extracellular pH in SCCHN.

Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening.

Matrix metalloproteinases (MMPs) are over-expressed in nearly all cancers. To study novel regulatory factors of MMP expression in head and neck cancer (HNC), we screened a total of 636 candidate genes encoding putative human transmembrane proteins using MMP promoter reporter in a dual luciferase assay system. Three genes GPR65, AXL and TNFRSF10B dramatically activated the induction of MMP3 expression. The induction of MMP expression by GPR65 was further confirmed in A549 and/or FaDu cells. GPR65 mediated MMP induction under acidic conditions. The AP-1 binding site in MMP3 promoter was crucial for MMP3 induction. Moreover, the A549 cells infected by recombinant adenovirus of GPR65 showed accelerated cell invasion. In conclusion, we validate that GPR65 is vital regulatory genes upstream of MMP3, and define a novel mechanism of MMP3 regulation by proton-sensing G-protein-coupled receptors.

Management of cervical lymph nodes for cN0 advanced glottic laryngeal carcinoma and its long-term results

Abstract Conclusions: Cervical lymph node metastatic rates tend to increase by T stage in cN0 glottic laryngeal carcinoma (GLC). Moreover, cervical lymph node metastasis (LNM) shows a sequential pattern according to the regions involved and LNM affects the prognosis. Objectives: To investigate factors that contribute to LNM of N0 (cN0) T2–T4 GLC and their effect on prognosis. Methods: A total of 212 GLC patients who had been admitted between December 2002 and January 2013 were retrospectively analyzed. They included 202 men and 10 women, median age 58.6 years (range 29–85 years), whose identified tumor stages included T2 (n = 81), T3 (n = 67), and T4 (n = 64). Relevant factors of cervical LNM were analyzed; multivariate analyses and receiver operating characteristic (ROC) curve were carried out to predict the metastasis and prognosis. Results: The overall metastatic rate of N0 GLC was 14.6%. T staging and pathological classification were the risk factors for LNM. Metastatic rates for levels II, III, and IV were 10.2%, 14.6%, and 2.5%, respectively. Approximate 4.2% of patients experienced LNM with no recurrence of laryngeal cancer. Overall 3- and 5-year survival rates were 85% and 80%, respectively, compared with 66% and 57%, respectively, among patients with LNM. The inter-group survival curve comparison was statistically significant (p = 0.012).

Clinicopathologic and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands: A clinical analysis of 130 cases

PURPOSE This study was to investigate clinicopathologic characteristics and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands. MATERIALS AND METHODS We conducted a retrospective review of 130 patients with adenoid cystic carcinoma of head and neck minor salivary glands that were evaluated between 2000 and 2013 in Beijng Tongren Hospital. RESULTS Five-year overall survival and disease-free survival rates were 80.8% and 55.6%. Local recurrence rate was 40%, regional recurrence 3.8%, and distant metastasis was 28.5%. On univariate analysis, solid histological subtype, perineural invasion, positive surgical margins and advanced stages were found to be poor prognostic indicators. On multivariate analysis, solid histological subtype and positive surgical margins were significant prognostic factors of worse overall survival. CONCLUSIONS Solid histological subtype and positive surgical margins were the most important predictors of poor outcome in adenoid cystic carcinoma of minor salivary glands. Surgery with postoperative radiation were recommended treatment and offered durable local control.

Factors contributing to lymph node occult metastasis in supraglottic laryngeal carcinoma cT2-T4 N0M0 and metastasis predictive equation

OBJECTIVE To investigate factors that contribute to lymph node metastasis (LNM) from clinical cT2-T4 N0M0 (cN0) supraglottic laryngeal carcinoma (SLC), and to predict the risk of occult metastasis before surgery. METHODS A total of 121 patients who received surgery were retrospectively analyzed. Relevant factors regarding cervical LNM were analyzed. Multivariate analyses were conducted to predict the region where the metastasis occurred and prognosis. RESULTS The overall metastatic rate of cN0 SLC was 28.1%. Metastatic rates were 15.4%, 32.5% and 35.7% for T2, T3 and T4, respectively. Metastatic rates for SLC levels II, III and IV were 19.6%, 17.2% and 3.6%, respectively. A regression equation was formulated to predict the probability of metastasis in cN0 SLC as follows: Pn=e((-3.874+0.749T3+1.154T4+1.935P1+1.750P2))/[1+e((-3.874+0.749T3+1.154T4+1.935P1+1.750P2))]. Approximately 0.2% of patients experienced LNM with no recurrence of laryngeal cancer. Comparison of the intergroup survival curves between patients with and without LNM indicated a statistically significant difference (P=0.029). CONCLUSIONS Cervical lymph node metastatic rates tended to increase in tandem with T stage in patients with LNM in cN0 SLC, and neck dissection is advised for these patients. Moreover, cervical LNM in cN0 SLC showed a sequential pattern and may be predicted.

Matched-pair analysis of survival in patients with poorly differentiated versus well-differentiated glottic squamous cell carcinoma

To compare survival outcomes between patients with poorly differentiated versus well-differentiated glottic squamous cell carcinoma (GSCC). Fifty-five patients with well-differentiated newly diagnosed GSCC were pair-matched to 55 patients with poorly differentiated GSCC according to age, sex, year of diagnosis, overall stage, treatment (surgery type, neck dissection, surgical margin, and chemoradiation), smoking, and alcohol use. Survival analysis was performed using Kaplan-Meier estimates, and matched-pair survival was estimated using the Cox proportional hazards regression model. Patients with well-differentiated GSCC had significantly better overall survival (OS) (P = 0.001), disease-specific survival (DSS) (P < 0.001), and disease-free survival (DFS) (P = 0.003) than patients with poorly differentiated GSCC. Moreover, matched-pair analysis indicated that increased differentiation was associated with a significantly reduced risk of overall death (HR, 0.18; 95% confidence interval [CI], 0.07–0.46), death owing to disease (HR, 0.16; 95% CI, 0.05–0.45), and disease recurrence (HR, 0.17; 95% CI, 0.07–0.41), and these risks were reduced approximately 4-fold, 3.7-fold, and 9-fold, respectively, after adjustment for cancer-associated variables. Survival differed significantly between the well-differentiated and poorly differentiated GSCC patients after adjustment for cancer prognosis-associated variables. Thus, identifying potential differences in the molecular characteristics between these two groups of patients would help to further stratify these patients and ensure appropriate individualized treatment decisions. Basing treatment strategies on the level of differentiation may improve survival.

Minimally Invasive Endoscopic Surgery of Thyroglossal Duct Cysts

PURPOSE Thyroglossal duct cysts (TGDCs) may cause cosmetic defects or more serious impairments if left untreated. Our study was designed to examine the potential advantage of endoscopic surgery performed on TGDCs, especially the ability to completely resect the branches and to affect the cosmetic appearance. PATIENTS AND METHODS Thirty-two patients from Beijing Tongren Hospital, Beijing, China, diagnosed with TGDCs were selected. Seventeen patients with TGDCs underwent traditional Sistrunks surgery, and 15 patients underwent endoscopic cystectomy. RESULTS All patients had complete resection and were followed up from 6 months to 4 years. None had a recurrence after endoscopic resection. However, patients in the traditional surgery group had a 5.9% (1/17) rate of recurrence. The incision length was approximately 2.1 cm in the endoscopic group compared with 5.2 cm in the traditional group. The mean time for the endoscopic operation was 97.7 minutes compared with 51.6 minutes in the traditional surgical procedure. The average length of hospital stay was 6.7 days in the endoscopic group compared with 9.7 days in the traditional group. CONCLUSIONS Endoscope-assisted small-incision thyroglossal duct cystectomy is an efficient method. It causes fewer cosmetic defects and also decreases operative time. It will likely become the new standard procedure for patients with TGDCs.