Wen-Lun Wang

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).

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.

Endoscopic submucosal dissection for early esophageal neoplasia: A single center experience in South Taiwan

BACKGROUND/PURPOSE Endoscopic submucosal dissection (ESD) is an advanced endoscopic procedure to resect early gastrointestinal neoplasm. It is technically more difficult and risky when used to treat early esophageal tumors. We report our experiences related to performing ESD for early esophageal neoplasia. The efficacy, complications, and outcome were also analyzed. METHODS From December 2007 to April 2010, 22 patients with documented early esophageal neoplasm underwent ESD. All patients completed a meticulous endoscopic examination using conventional endoscopy followed by narrow-band imaging. Lugols staining was performed to identify the margin of the suspicious lesion. Insulation-tipped diathermic knife 2 was used for ESD. RESULTS A total of 26 neoplastic lesions (including 13 tumors with high-grade dysplasia, 12 tumors with squamous cell carcinoma, and one tumor with adenocarcinoma) in 22 patients were enrolled. All patients were men. The mean age was 47.6 ± 8.6 years (range, 30-68 years). The mean size of tumors was 33.7 ± 21.7 mm (range, 8-80 mm). ESD was performed for 24 lesions in 20 patients. The mean size of resected specimens was 43.1 ± 19.2 mm (range, 15-90 mm). The mean operation time was 92.7 ± 69 minutes (range, 30-310 minutes). There were three ESD-related complications, including one with delayed bleeding, one with subcutaneous emphysema, and one with perforation. Two patients received additional operations after ESD due to deep submucosal invasion by cancer. Three lesions in two patients (12.5%) developed post-ESD esophageal stricture that needed repeated endoscopic bougination. There was no procedure-related mortality. No local recurrence was found during the follow-up period. CONCLUSION ESD is a promising local curative treatment option for early esophageal neoplasia in Taiwan. However, this procedure may result in complications that are worth noting, especially post-ESD esophageal stricture. Education regarding this procedure and more hands-on training will facilitate endoscopists to improve the outcomes of patients undergoing this procedure.

The benefit of pretreatment esophageal screening with image-enhanced endoscopy on the survival of patients with hypopharyngeal cancer.

BACKGROUND Synchronous esophageal cancers can suppress the survival of patients with hypopharyngeal cancers. Esophageal screening with the image-enhanced endoscopy may identify more synchronous cancers while there is no evidence to support its benefit on survival. METHODS A total of 281 and 320 patients were diagnosed with hypopharyngeal cancer before and after the policy of routine esophageal screening. Primary outcome measures were overall survival. RESULTS Among those who received screening, 49 patients (49/180, 27.2%) had synchronous esophageal cancers; treatment planning was changed in 42 (23.3%). Before and after the policy, percentages of stage I-II synchronous cancers were 20% (3/15) and 53.1% (26/49), respectively. Adjunctive therapies for synchronous cancers have led to a better survival after the policy than before (P = 0.002). The Cox regression model quantified a survival benefit of 29% (95% CI: 11-43%) when adjusting for TNM stage of hypopharyngeal cancer. In post-policy period, the survival was better for those who chose screening than those who did not (HR: 0.57, 95% CI: 0.41-0.79). Among those without screening, there was no difference between the pre- and post-policy periods (HR: 0.96, 95% CI: 0.74-1.26). CONCLUSIONS Patients with hypopharyngeal cancers may benefit from the esophageal screening with image-enhanced endoscopy through the better detection of early-stage synchronous cancers.

Circumferential balloon-based radiofrequency ablation for ultralong and extensive flat esophageal squamous neoplasia

Esophageal cancer is highly lethal and causes more than 400,000 deaths per year worldwide. In the Asia-Pacific region, esophageal squamous cell carcinoma is the major form of the disease, and its incidence is increasing. Recent advances in image-enhanced endoscopy have led to earlier diagnosis of esophageal squamous mucosal cancer or precancerous lesions. Endoscopic submucosal dissection (ESD) enables large en bloc resection of these superficial esophageal cancers, but the technique is complicated and requires considerable expertise. In particular, when there are large lesions or lesions that occupy more than threefourths of the circumference of the esophagus, patients will have esophageal stenosis. Stenosis can decrease quality of life, and treatment requires multiple sessions of endoscopic balloon dilation. Therefore, it is important to have an alternative and more convenient method to treat these large and extensive esophageal squamous neoplasias. Radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality, and recent studies have shown its efficacy and safety for eradicating high-grade dysplasia in cases of Barrett’s esophagus. RFA also has theoretical potential for treating squamous epithelial neoplasias. However, only a few studies have demonstrated the potential efficacy for squamous neoplasia, and no studies have

Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia

AbstractRadiofrequency ablation (RFA) and endoscopic submucosal dissection (ESD) can potentially be applied for early esophageal squamous cell neoplasia (ESCN); however, no study has directly compared these 2 modalities.We retrospectively enrolled the patients with flat-type “large” (length ≥3 cm extending ≥1/2 of the circumference of esophagus) early ESCNs treated endoscopically. The main outcome measurements were complete response at 12 months, and adverse events.Of a total of 65 patients, 18 were treated with RFA and 47 with ESD. The procedure time of RFA was significantly shorter than that of ESD (126.6 vs 34.8 min; P < 0.001). The complete resection rate of ESD and complete response rate after primary RFA were 89.3% and 77.8%, respectively. Based on the histological evaluation of the post-ESD specimens showed 14 of 47 (29.8%) had histological upstaging compared with the pre-ESD biopsies, and 4 of them had lymphovascular invasion requiring chemoradiation or surgery. After additional therapy for residual lesions, 46 (97.9%) patients in the ESD group and 17 (94.4%) patients in the RFA group achieved a complete response at 12 months. Four patients (8.5%) developed major procedure-related adverse events in the ESD group, but none in the RFA group. In patients with lesions occupying more than 3/4 of the circumference, a significantly higher risk of esophageal stenosis was noted in the ESD group compared with RFA group (83% vs 27%, P = 0.01), which required more sessions of dilatation to resolve the symptoms (median, 13 vs 3, P = 0.04). There were no procedure-related mortality or neoplastic progression in either group; however, 1 patient who received ESD and 1 who received RFA developed local recurrence during a median follow-up period of 32.4 (range, 13–68) and 18.0 (range, 13–41) months, respectively.RFA and ESD are equally effective in the short-term treatment of early flat large ESCNs; however, more adverse events occur with ESD, especially in lesions extending more than 3/4 of the circumference. RFA does not allow for pathology to evaluate the curability after ablation, and thus currently the use for invasive ESCNs should be conservative until longer follow-up studies are available.

Narrow-band imaging and white-light endoscopy with optical magnification in the diagnosis of dysplasia in Barrett’s esophagus: results of the Asia-Pacific Barrett’s Consortium

Objective: The advent and utility of new endoscopic imaging modalities for predicting the histology of Barrett’s esophagus (BE) in real time with high accuracy appear promising and could potentially obviate the need to perform random biopsies where guidelines are poorly adhered to. We embarked on evaluating the performance characteristics of white-light endoscopy with magnification (WLE-z), narrow-band imaging with magnification (NBI-z) and a combination of both modalities. Design: This was a prospective online study with 28 endoscopists from 11 countries (Asia-Pacific region) participating as assessors. In total, 35 patients with BE were assessed using 150 slides from WLE-z and NBI-z randomly arranged using a simple classification with corresponding histology. The overall Accuracy (Acc), Sensitivity (Sn), Specificity (Sp), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of WLE-z, NBI-z and a combination of both were calculated. Results: The overall Acc for WLE-z and NBI-z images was 87.1 % and 88.7 %, respectively. When images from the two modalities were placed side by side, the Acc increased to 90.3 %. The Sn, Sp, PPV, and NPV of WLE-z were 48 %, 92 %, 45 %, and 93 % while with NBI-z, these improved to 89 %, 89 %, 56 %, and 98 %, respectively. When both imaging modalities were viewed together, they improved further to 93 %, 90 %, 61 %, and 99 %. Conclusion: The high NPV (99 %) when both WLE-z and NBI-z were used simultaneously indicates that areas with regular appearance that are diagnosed with confidence can effectively be left alone and not biopsied when performed at a skilled resourced center. This approach could potentially lead to a paradigm shift of how patients with BE are assessed.

The impact of human papillomavirus infection on the survival and treatment response of patients with esophageal cancers

This study aimed to investigate the impact of human papillomavirus (HPV) infection on the prognosis and treatment response of esophageal squamous cell carcinoma (ESCC).

Predictors for postoperative esophageal stricture after balloon-based radiofrequency ablation for early esophageal squamous neoplasia: a multicenter validation study

Background: Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early flat esophageal squamous cell neoplasms (ESCNs), but the risk factors for postoperative stricture have not been elucidated. The objective of this study was to identify and validate a predictor for post-RFA stenosis. Methods: We consecutively enrolled patients with flat-type ‘large’ (length no less than 3 cm extending no less than half the circumference of the esophagus), early ESCNs, treated with balloon-based RFA (12 J/cm2–clean–12 J/cm2 regimen). The tumor and technical factors for postoperative stricture were investigated and we validated the results externally with a society-based multicenter cohort using the same ablation regimen. Results: A total of 51 patients were enrolled (30 in the development set and 21 in the validation set). The complete remission rate at 12 months was 93%, and the rates of perforation and postoperative stenosis were 0% and 17%, respectively. Patients with post-RFA stenosis had a significantly larger longitudinal tumor size (mean 115 versus 61 mm, p = 0.003). There were no significant differences in age, body mass index, tumor circumferential extension, pretreatment histological grade, treatment efficacy or size of balloon catheter between the groups with or without stenosis. The optimal cut-off value was set as 9 cm to predict post-RFA stenosis by receiver operating characteristic curve [area under curve (AUC) = 0.881], which was then confirmed to be a reliable predictor by multivariate analysis (odds ratio, 12.7, 95% confidence interval, 1.18–136.28, p = 0.03) and have a good predictive performance in the validation set (AUC = 0.876). Conclusions: The most frequent adverse event of RFA was esophageal stenosis, for which the longitudinal tumor size was a significant predictive factor. Early intervention or prevention for stricture should be applied for those with long segment (⩾9 cm) ESCNs.

Prospective Survey for the Etiology and Outcome of Peptic Ulcer Bleeding: A Community Based Study in Southern Taiwan

BACKGROUND/PURPOSE Helicobacter pylori infection and drugs are the two major risk factors for peptic ulcer bleeding. The role of these two factors may change with changes in the prevalence of H pylori and use of NSAIDs. This study aimed to determine the cause, endoscopic features, and outcome of peptic ulcer bleeding in a community hospital in southern Taiwan. METHODS Patients who received esophagogastroduodenoscopy on arrival at the emergency department and were found to have actively bleeding ulcers or ulcers with stigmata of recent hemorrhage were included. H pylori infection was documented by the rapid urease test, histology, and/or C-13 urease breath test. Medication history, comorbidities, requirement for endoscopic therapy, blood transfusion, hospitalization days, and rebleeding rates were analyzed. RESULTS A total of 204 patients were enrolled with a mean age of 64.8 ± 15.2 years, with 58.3% of the subjects being female. There were 62 patients (30.4%) with H pylori infection only, 40 patients (19.6%) with drug use only, 67 patients (32.8%) with H pylori infection and drug use, and 37 patients (17.2%) without H pylori or drug use. A total of 107 patients (52.5%) were found to have had drug exposure. Drug exposure had an odds ratio (OR) of 2.34 [95% Confidence Interval (CI) = 1.30-4.20] for gastric ulcer bleeding and H pylori had an OR of 2.64 (95% CI = 1.17-5.97) for combined gastric and duodenal ulcer bleeding. The mean hospitalization period was 5.7 ± 4.0 days and the overall re-bleeding rate was 4.0%. The H pylori negative and drug negative subjects needed more endoscopic therapy (p < 0.05). CONCLUSION Drug use, especially NSAIDs, aspirin, and clopidogrel has become an important cause of peptic ulcer bleeding in southern Taiwan.