Cheng-Ping Wang

Genetic predisposition factors and nasopharyngeal carcinoma risk: a review of epidemiological association studies, 2000-2011: Rosetta Stone for NPC: genetics, viral infection, and other environmental factors.

While infection with Epstein-Barr virus (EBV) is known to be an essential risk factor for the development of nasopharyngeal carcinoma (NPC), other co-factors including genetic factors are thought to play an important role. In this review, we summarize association studies conducted over the past decade to evaluate the role of genetic polymorphisms in NPC development. A review of the literature identified close to 100 studies, including 3 genome-wide association studies (GWAS), since 2000 that evaluated genetic polymorphisms and NPC risk in at least 100 NPC cases and 100 controls. Consistent evidence for associations were reported for a handful of genes, including immune-related HLA Class I genes, DNA repair gene RAD51L1, cell cycle control genes MDM2 and TP53, and cell adhesion/migration gene MMP2. However, for most of the genes evaluated, there was no effort to replicate findings and studies were largely modest in size, typically consisting of no more than a few hundred cases and controls. The small size of most studies, and the lack of attempts at replication have limited progress in understanding the genetics of NPC. Moving forward, if we are to advance our understanding of genetic factors involved in the development of NPC, and of the impact of gene-gene and gene-environment interations in the development of this disease, consortial efforts that pool across multiple, well-designed and coordinated efforts will most likely be required.

Vascular Leiomyoma of the Head and Neck

Objectives/Hypothesis Vascular leiomyoma, a benign tumor composed of smooth muscle cell and vascular endothelium, is rare in the head and neck region. The authors report their experience with 21 patients.

Transnasal endoscopy with narrow-band imaging and Lugol staining to screen patients with head and neck cancer whose condition limits oral intubation with standard endoscope (with video)

BACKGROUND Early detection of esophageal cancer in patients with head and neck cancers may alter treatment planning and improve survival. However, standard endoscopic screening is not feasible for some patients with tumor-related airway compromise or postirradiation trismus. OBJECTIVE To evaluate a novel, sequential approach by integrating ultrathin endoscopy with narrow-band imaging and Lugol chromoendoscopy. DESIGN Cross-sectional study. SETTING Single center in Taiwan. PATIENTS Forty-four consecutive patients with transoral difficulty screened for synchronous or metachronous esophageal cancer. MAIN OUTCOME MEASUREMENTS Sensitivity, specificity, and accuracy in the detection of mucosal high-grade neoplasia or invasive cancer. RESULTS Fifty-four endoscopic interpretations were obtained, and 11 mucosal high-grade neoplasia and 7 invasive cancers were confirmed by histology. The mean examination time was 19.4 minutes (range 7.9-35.2 minutes), and all patients tolerated the procedure well. Sensitivity, specificity, and accuracy (with 95% CI) were 55.6% (95% CI, 33.5%-75.6%), 97.2% (95% CI, 85.8%-99.3%), and 83.3% (95% CI, 71.2%-90.9%), respectively, for standard endoscopy; 88.9% (95% CI, 66.9%-96.6%), 97.2% (95% CI, 85.8%-99.3%), and 94.4% (95% CI, 84.9%-97.9%), respectively, with the adjunct of narrow-band imaging; and 88.9% (95% CI, 66.9%-96.6%), 72.2% (95% CI, 55.9%-84.1%), and 77.8% (95% CI, 64.9%-86.8%), respectively, with the adjunct of Lugol chromoendoscopy. When we integrated all interpretations on the basis of the sequential approach, the estimated probability of false-negative findings was 1.2% (95% CI, 0.1%-4.6%). LIMITATIONS Inherent shortcomings of ultrathin endoscopy, such as its resolution, light source, and lack of magnification. CONCLUSIONS The use of ultrathin endoscopy in a sequential approach for multimodal detection is feasible in patients with transoral difficulty and substantially increases the detection rate of synchronous or metachronous neoplasms.

Transcutaneous ultrasound for evaluation of vocal fold movement in patients with thyroid disease

BACKGROUND Preoperative evaluation of recurrent laryngeal nerve function is important in the context of thyroid surgery. Transcutaneous ultrasound may be useful to visualize vocal fold movement when evaluating thyroid disease. METHODS A 7-18 MHz linear array transducer was placed transversely on the midline of the thyroid cartilage at the anterior neck of patients with thyroid disease. The gray-scale technique was used, with the scan setting for the thyroid gland. RESULTS Between August 2008 and March 2010, 705 patients, including 672 patients with normal vocal fold movement and 33 patients with vocal fold paralysis were enrolled. They included 159 male and 546 female patients. Their ages ranged from 10 to 88 years. Vocal fold movement could be seen by ultrasound in 614 (87%) patients, including 589 (88%) patients with normal vocal fold movement and 25 (76%) patients with vocal fold paralysis (p=0.06). The mean age of patients with visible and invisible vocal fold movement was 46.6 and 57.9 years old, respectively (p=0.001). Ultrasound was able to see vocal fold movement in 533 (98%) female patients but only in 81 (51%) male patients (p=0.001). Among the patients with vocal fold paralysis, ultrasound revealed palsied vocal folds in 17 of 18 (94%) female patients but in only 8 of 15 (53%) male patients (p=0.01). CONCLUSION Transcutaneous ultrasound represents an alternative tool to evaluate vocal fold movement for more than 85% of patients with thyroid disease, including more than 90% of female patients and about half of male patients.

RISK FACTORS FOR DEVELOPING SYNCHRONOUS ESOPHAGEAL NEOPLASIA IN PATIENTS WITH HEAD AND NECK CANCER

This study investigated the risk factors for synchronous esophageal neoplasia in patients with head and neck squamous cell carcinoma (HNSCC).

Desmoid tumor of the head and neck

Desmoid tumors are rare benign tumors but have a tendency toward local recurrence after resection because of their infiltrative growth and frequent entrapment of vital structures in the head and neck region. We report 24 desmoid tumors of the head and neck and propose a reasonable approach in the management of such cases.

Intratympanic steroid injections as a salvage treatment for sudden sensorineural hearing loss: a randomized, double-blind, placebo-controlled study.

Objective: The purpose of this study was to determine, through a randomized, double-blind, placebo-controlled trial, whether intratympanic steroid injections (ITSIs) could improve hearing recovery in patients with sudden sensorineural hearing loss (SSHL) who did not respond to initial systemic steroid therapy. Study Design: This was a prospective, randomized, double-blind, placebo-controlled study. Setting: The study was conducted in 2 tertiary referral centers. Patients: A total of 60 patients with idiopathic SSHL who did not respond to an initial round of systemic steroid therapy were included in this study. The subjects were randomized into an ITSI group and an intratympanic normal saline injection (ITNI) group, which were matched by age and sex. A total of 55 subjects completed the study. Intervention: Participants received either ITSIs or ITNIs. Both groups received 4 injections within a 2-week period. Main Outcome Measures: Pure-tone thresholds were compared between the 2 groups 1 month after injection therapy. Results: In the ITNI group, the pure-tone threshold was 69.9 ± 18.5 dB before intratympanic injection therapy. After therapy, the hearing threshold improved by an average of 4.5 ± 6.5 dB, and 10.7% of subjects improved by 10 dB or more. In the ITSI group, the pure-tone threshold was 64.6 ± 17.7 dB before intratympanic injection therapy. After the therapy, the hearing threshold improved by an average of 9.8 ± 8.5 dB, and 44.4% of subjects improved by 10 dB or more. Both the response rate and the level of hearing improvement were significantly greater in the ITSI group than in the ITNI group. Conclusion: These results demonstrate that ITSIs are beneficial as a salvage therapy for the treatment of patients with idiopathic SSHL who fail to respond to initial systemic steroid therapy.

Secondary prevention of esophageal squamous cell carcinoma in areas where smoking, alcohol, and betel quid chewing are prevalent.

Esophageal cancer is ranked as the sixth most common cause of cancer death worldwide and has a substantial effect on public health. In contrast to adenocarcinoma arising from Barretts esophagus in Western countries, the major disease phenotype in the Asia-Pacific region is esophageal squamous cell carcinoma which is attributed to the prevalence of smoking, alcohol, and betel quid chewing. Despite a multidisciplinary approach to treating esophageal cancer, the outcome remains poor. Moreover, field cancerization reveals that esophageal squamous cell carcinoma is closely linked with the development of head and neck cancers that further sub-optimize the treatment of patients. Therefore, preventive strategies are of paramount importance to improve the prognosis of this dismal disease. Since obstacles exist for primary prevention via risk factor elimination, the current rationale for esophageal cancer prevention is to identify high-risk groups at earlier stages of the disease, and encourage them to get a confirmatory diagnosis, prompt treatment, and intensive surveillance for secondary prevention. Novel biomarkers for identifying specific at-risk populations are under extensive investigation. Advances in image-enhanced endoscopy do not just substantially improve our ability to identify small precancerous or cancerous foci, but can also accurately predict their invasiveness. Research input from the basic sciences should be translated into preventive measures in order to decrease the disease burden of esophageal cancer.

Revisit of Field Cancerization in Squamous Cell Carcinoma of Upper Aerodigestive Tract: Better Risk Assessment with Epigenetic Markers

We quantified field cancerization of squamous cell carcinoma in the upper aerodigestive tract with epigenetic markers and evaluated their performance for risk assessment. Methylation levels were analyzed by quantitative methylation-specific PCR of biopsied specimens from a training set of 255 patients and a validation set of 224 patients. We also measured traditional risk factors based on demographics, lifestyle, serology, genetic polymorphisms, and endoscopy. The methylation levels of four markers increased stepwise, with the lowest levels in normal esophageal mucosae from healthy subjects without carcinogen exposure, then normal mucosae from healthy subjects with carcinogen exposure, then normal mucosae from cancer patients, and the highest levels were in cancerous mucosae (P < 0.05). Cumulative exposure to alcohol increased methylation of homeobox A9 in normal mucosae (P < 0.01). Drinkers had higher methylation of ubiquitin carboxyl-terminal esterase L1 and metallothionein 1M (P < 0.05), and users of betel quid had higher methylation of homeobox A9 (P = 0.01). Smokers had increased methylation of all four markers (P < 0.05). Traditional risk factors allowed us to discriminate between patients with and without cancers with 74% sensitivity (95% CI: 67%–81%), 74% specificity (66%–82%), and 80% area under the curve (67%–91%); epigenetic markers in normal esophageal mucosa had values of 74% (69%–79%), 75% (67%–83%), and 83% (79%–87%); and both together had values of 82% (76%–88%), 81% (74%–88%), and 91% (88%–94%). Epigenetic markers done well in the validation set with 80% area under the curve (73%–85%). We concluded that epigenetics could improve the accuracies of risk assessment. Cancer Prev Res; 4(12); 1982–92. ©2011 AACR.

Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families.

Purpose: Epstein–Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families. Experimental Design: We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated. Results: A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4–16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5–61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker. Conclusions: Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity. Clin Cancer Res; 17(7); 1906–14. ©2011 AACR.