Pink-color sign in esophageal squamous neoplasia, and speculation regarding the underlying mechanism

AIM:To investigate the reasons for the occurrence of the pink-color sign of iodine-unstained lesions. METHODS:In chromoendoscopy, the pink-color sign of iodine-unstained lesions is recognized as useful for the diagnosis of esophageal squamous cell carcinoma. Patients with superficial esophageal neoplasms treated by endoscopic resection were included in the study. Areas of mucosa with and without the pink-color sign were evaluated histologically. The following histologic features that were possibly associated with the pinkcolor sign were evaluated. The keratinous layer and basal cell layer were classified as present or absent. Cellular atypia was classified as high grade, moderate grade or low grade, based on nuclear irregularity, mitotic figures, loss of polarity, chromatin pattern and nuclear/cytoplasmic ratio. Vascular change was assessed based on dilatation, tortuosity, caliber change and variability in shape. Vessels with these four findings were classified as positive for vascular change. Endoscopic images of the lesions were captured immediately after iodine staining, 2-3 min after iodine staining and after complete fading of iodine staining. Quantitative analysis of color changes after iodine staining was also performed. RESULTS:A total of 61 superficial esophageal neoplasms in 54 patients were included in the study. The lesions were located in the cervical esophagus in one case, the upper thoracic esophagus in 10 cases, the mid-thoracic esophagus in 33 cases, and the lower thoracic esophagus in 17 cases. The median diameter of the lesions was 20 mm (range:2-74 mm). Of the 61 lesions, 28 were classified as pink-color sign positive and 33 as pink-color sign negative. The histologic diagnosis was high-grade intraepithelial neoplasia (HGIN) or cancer invading into the lamina propria in 26 of the 28 pink-color sign positive lesions. There was a significant association between pink-color sign positive epithelium and HGIN or invasive cancer (P = 0.0001). Univariate analyses found that absence of the keratinous layer and cellular atypia were significantly associated with the pink-color sign. After Bonferroni correction, there were no significant associations between the pink-color sign and presence of the basal membrane or vascular change. Multivariate analyses found that only absence of the keratinous layer was independently associated with the pink-color sign (OR = 58.8, 95%CI:5.5-632).Quantitative analysis was performed on 10 superficial esophageal neoplasms with both pink-color sign positive and negative areas in 10 patients. Pink-color sign positive mucosa had a lower mean color value in the late phase (pinkish color) than in the early phase (yellowish color), and had similar mean color values in the late and final phases. These findings suggest that pinkcolor positive mucosa underwent color fading from the color of the iodine (yellow) to the color of the mucosa (pink) within 2-3 min after iodine staining. Pink-color sign negative mucosa had similar mean color values in the late and early phases (yellowish color), and had a lower mean color value in the final phase (pinkish color) than in the late phase. These findings suggest that pink-color sign negative mucosa did not undergo color fading during the 2-3 min after iodine staining, and underwent color fading only after spraying of sodium thiosulfate. CONCLUSION:The pink-color sign was associated with absence of the keratinous layer. This sign may be caused by early fading of iodine staining.

Feasibility of cold snare polypectomy in Japan: A pilot study

AIM: To investigate the feasibility of cold snare polypectomy(CSP) in Japan.METHODS: The outcomes of 234 non-pedunculated polyps smaller than 10 mm in 61 patients who underwent CSP in a Japanese referral center were retrospectively analyzed. The cold snare polypectomies were performed by nine endoscopists with no prior experience in CSP using an electrosurgical snare without electrocautery.RESULTS: CSPs were completed for 232 of the 234 polyps. Two(0.9%) polyps could not be removed without electrocautery. Immediate postpolypectomy bleeding requiring endoscopic hemostasis occurred in eight lesions(3.4%; 95%CI: 1.1%-5.8%), but all were easily managed. The incidence of immediate bleeding after CSP for small polyps(6-9 mm) was significantly higher than that of diminutive polyps(≤ 5 mm; 15% vs 1%, respectively). Three(5%) patients complained of minor bleeding after the procedure but required no intervention. The incidence of delayed bleeding requiringendoscopic intervention was 0.0%(95%CI: 0.0%-1.7%). In total, 12% of the resected lesions could not be retrieved for pathological examination. Tumor involvement in the lateral margin could not be histologically assessed in 70(40%) lesions.CONCLUSION: CSP is feasible in Japan. However, immediate bleeding, retrieval failure and uncertain assessment of the lateral tumor margin should not be underestimated. Careful endoscopic diagnosis before and evaluation of the tumor residue after CSP are recommended when implementing CSP in Japan.

Salvage Photodynamic Therapy Is an Effective and Safe Treatment for Patients with Local Failure after Definitive Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

Although chemoradiotherapy (CRT) is one curative treatment option for patients with esophageal squamous cell carcinoma (ESCC), local failure after CRT remains a major problem for patients’ curability. The aim of this study was to evaluate the efficacy and safety of photodynamic therapy (PDT) as a salvage treatment for local failure. From August 2007 to March 2012, 193 consecutive ESCC patients were treated with definitive CRT in Kyoto University Hospital. Eighteen of the patients with T2 or earlier T-stage local failure after CRT underwent salvage PDT. After the salvage PDT, 11 patients (61.1%) achieved a complete response at the primary site. Over a median follow-up period of 28.3 months, the 1-year survival and progression-free survival rates were 77.8% and 38.9%, respectively;and the 2-year survival and progression-free survival rates were 60.6% and 33.3%, respectively. Adverse events were mild esophageal stricture in seven (38.9%), esophageal obstruction because of necrotic tissue in nine (50.0%), and photosensitivity in three (16.7%) patients. There were no severe complications or treatment-related deaths. Salvage PDT may be a promising treatment option for the patients with a local residual or recurrent tumor after CRT for ESCC when the lesion is suspected to be in T2 or earlier.