Jenq-Yuh Ko

Dysphagia after radiotherapy : Endoscopic examination of swallowing in patients with nasopharyngeal carcinoma

Dysphagia is a late sequela compromising the lives of more than one fourth of patients with nasopharyngeal carcinoma (NPC) who survive long after radiotherapy. By using fiberoptic endoscopic examination of swallowing as a modality for dysphagia evaluation, we were able to easily recognize the functional and anatomic changes in 31 dysphagic NPC patients. The majority of patients were found to aspirate after the act of swallowing (77.4%). Seventeen (54.8%) had tongue atrophy, and 9 (29%) had vocal cord palsy. Dysfunctions such as dry mouth (45.2%), velopharyngeal incompetence (58%), premature leakage (41.9%), delay or absence of swallow reflex (87.1%), poor pharyngeal constriction (80.6%), pharyngeal residue retention (83.9%), penetration or aspiration (93.5%), and silent aspiration (41.9%) were noted in these patients. Multiple dysfunctions were demonstrated in each patient. Abnormality of pharyngeal constriction and/or aberrant upper esophageal sphincter function played the major role in the postswallow aspiration of these irradiated NPC patients. Clinically compromised patients (weight loss of ≥5 kg in 1 year or pneumonia) had more of the above anatomic and functional impairments. The radiation dosage and volume bore no correlation to the time of symptom onset, or to the occurrence of functional changes.

Induction Chemotherapy With Mitomycin, Epirubicin, Cisplatin, Fluorouracil, and Leucovorin Followed by Radiotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma

PURPOSE Survival in advanced nasopharyngeal carcinoma (NPC) is compromised by distant metastasis. Because mitomycin is active against hypoxic and G0 cells, which may help to eradicate micrometastasis, we investigated the effect of mitomycin-containing cisplatin-based induction chemotherapy. PATIENTS AND METHODS Recruited for this study were American Joint Committee on Cancer (AJCC) 1992 staging system stage IV NPC patients with the following adverse features: obvious intracranial invasion, supraclavicular or bilateral neck lymph node metastasis, large neck node (> 6 cm), or elevated serum lactate dehydrogenase (LDH) level. Patients were given three cycles of chemotherapy before radiotherapy. The chemotherapy comprised a 3-week cycle of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL). RESULTS From January 1994 to December 1997, 111 patients were recruited. The median follow-up period was 43 months. The actuarial 5-year overall survival rate was 70% (95% confidence interval [CI], 60% to 80%; n = 111). For patients having completed radiotherapy (n = 100), the 5-year locoregional control rate was 70% (95% CI, 55% to 84%) and the distant metastasis-free rate was 81% (95% CI, 73% to 89%). The 5-year distant metastasis-free rate of N3a and N3b disease of AJCC 1997 staging system were 79% (95% CI, 62% to 95%) and 74% (95% CI, 60% to 89%), respectively. By Cox multivariate analysis, high pretreatment serum LDH level (P = .04) and neck nodal enlargement before radiotherapy (P = .001) were adverse prognostic factors of survival. CONCLUSION The good 5-year survival of N3 disease supports the effectiveness of induction MEPFL in the primary treatment of advanced NPC. Further investigation to incorporate concurrent chemoradiotherapy is warranted.

CXCL12/CXCR4 promotes laryngeal and hypopharyngeal squamous cell carcinoma metastasis through MMP-13-dependent invasion via the ERK1/2/AP-1 pathway

Laryngeal and hypopharyngeal squamous cell carcinomas (LHSCCs) are common head and neck cancers with a high propensity for lymph node (LN) and lung metastasis. Here, we report that LHSCCs express high levels of functional CXCR4 receptors, native for chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). Primary tumor immunohistochemistry from LHSCC patients has revealed significant expression of CXCR4 and CXCL12. Greater expression of CXCR4 but not that of CXCL12 is correlated with LN and distant metastasis. Reverse transcription-polymerase chain reaction and western blots have demonstrated that CXCR4 messenger RNA (mRNA) and protein were expressed in LHSCC cell lines as well, but failed to detect CXCL12 mRNA expression. CXCL12 treatment enhanced extracellular signal-regulated kinase (ERK) pathway activation and the motility/invasiveness of LHSCC cell lines, which were blocked by treatment with a CXCR4 antagonist (AMD3100) and a specific MEK inhibitor (U0126). Results show that the mRNA and protein levels of matrix metalloproteinase (MMP)-13, but not MMP-2 or MMP-9, were elevated in HEp-2 cells in response to CXCL12. Again, U0126 almost inhibited the induction of MMP-13 in HEp-2 cells by stimulating CXCL12. The transcriptional factor, c-Jun, a downstream factor of ERK pathway, was found to be readily phosphorylated and translocated to the nucleus after 10 min of exposure to CXCL12. Blockage of c-Jun activity by transfection with c-jun antisense oligodeoxynucleotide significantly decreased CXCL12-induced MMP-13 expression and cell invasion. CXCL12 seems to enhance LHSCC cell invasion through paracrine-activated CXCR4, which triggers ERK/c-Jun-dependent MMP-13 upregulation.

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).

Lymphoepithelial Carcinoma versus Large Cell Undifferentiated Carcinoma of the Major Salivary Glands

Undifferentiated carcinomas of the major salivary glands are rare malignant neoplasms of the head and neck region, and patients with these lesions have a poor prognosis. Patients with lymphoepithelial carcinoma (LEC), a specific subtype of undifferentiated carcinoma, however, have a better prognosis, and LEC seems to differ from large cell undifferentiated carcinoma (LCUC) clinically.

Epstein‐Barr Virus‐encoded Latent Membrane Protein 1 Co‐expresses with Epidermal Growth Factor Receptor in Nasopharyngeal Carcinoma

Latent membrane protein 1 (LMP‐1) is the only Epstein‐Barr virus (EBV)‐encoded oncogenic protein that has been detected in nasopharyngeal carcinoma (NPC), a cancer that is closely associated with EBV. Previous in‐vitro studies have demonstrated that LMP‐1 can upregulate epidermal growth factor receptor (EGFR) in epithelial cells. It was not established whether this cellular effect exists in NPC. To assess the association between LMP‐1 and EGFR in NPC tissues, 60 NPC specimens were examined by immunohistochemistry using anti‐LMP‐1 antibody (CS 1–4) and anti‐EGFR antibodies (EGFR 1, EGFR 1005). The results revealed that 41 (68.3%) specimens were immunopositive for LMP‐1 and 44 (73.3%) specimens over‐expressed EGFR. Morphologically, the expressions of LMP‐1 and EGFR were homogeneously distributed in the tumor nests. In addition, the correlation between LMP‐1 and EGFR was statistically significant (P<0.001, χ2 test, d.f.=1). To elucidate further the correlation between LMP‐1 and EGFR in vivo and in situ, an indirect dual immunofluorescence assay was conducted, using secondary antibodies conjugated with fluorescein isothiocyanate (FITC) or indocarbocyanine (Cy3). The results disclosed an intimate co‐expression of LMP‐1 and EGFR. In summary, the data indicate that over‐expression of EGFR is a common phenomenon in NPC, and that EGFR is co‐expressed with LMP‐1 in NPC. Thus, EBV may play a role in the tumorigenesis of NPC through the effects of LMP‐1 and EGFR.

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.

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.