Yasumasa Ezoe

Magnifying narrowband imaging is more accurate than conventional white-light imaging in diagnosis of gastric mucosal cancer.

BACKGROUND & AIMS It is difficult to accurately diagnose patients with depressed gastric mucosal cancer based on conventional white-light imaging (C-WLI) endoscopy. We compared the real-time diagnostic yield of C-WLI for small, depressed gastric mucosal cancers with that of magnifying narrow-band imaging (M-NBI). METHODS We performed a multicenter, prospective, randomized, controlled trial of patients with undiagnosed depressed lesions ≤10 mm in diameter identified by esophagogastroduodenoscopy. Patients were randomly assigned to groups that were analyzed by C-WLI (n = 176) or M-NBI (n = 177) immediately after detection; the C-WLI group received M-NBI after C-WLI. We compared the diagnostic accuracy, sensitivity, and specificity between C-WLI and M-NBI and assessed the diagnostic yield of M-NBI conducted in conjunction with C-WLI. RESULTS Overall, 40 gastric cancers (20 in each group) were identified. The median diagnostic values for M-NBI and C-WLI were as follows: accuracy, 90.4% and 64.8%; sensitivity, 60.0% and 40.0%; and specificity, 94.3% and 67.9%, respectively. The accuracy and specificity of M-NBI were greater than those of C-WLI (P < .001); the difference in sensitivity was not significant (P = .34). The combination of M-NBI with C-WLI significantly enhanced performance compared with C-WLI alone; accuracy increased from (median) 64.8% to 96.6% (P < .001), sensitivity increased from 40.0% to 95.0% (P < .001), and specificity increased from 67.9% to 96.8% (P < .001). CONCLUSIONS M-NBI, in conjunction with C-WLI, identifies small, depressed gastric mucosal cancers with 96.6% accuracy, 95.0% sensitivity, and 96.8% specificity. These values are better than for C-WLI or M-NBI alone.

Magnifying narrow-band imaging versus magnifying white-light imaging for the differential diagnosis of gastric small depressive lesions: a prospective study

BACKGROUND The accurate diagnosis of gastric small depressive lesions (SDLs), including gastritis and cancerous lesions, is difficult with conventional endoscopy when using white-light imaging (WLI). Narrow-band imaging (NBI) is expected to make a more accurate diagnosis of gastric SDLs than WLI because it provides better visualization of the mucosal surface and microvascular architecture when combined with magnifying endoscopy. OBJECTIVE To compare the real-time diagnostic accuracy of magnifying WLI and magnifying NBI for gastric SDLs. DESIGN Prospective study. SETTING National Cancer Center Hospital East, Kashiwa, Japan. PATIENTS Fifty-seven lesions in 53 consecutive patients were analyzed: 30 cancers and 27 benign lesions. INTERVENTIONS If previously undiagnosed gastric SDLs smaller than 10 mm were identified during an endoscopic examination, magnifying observation with both WLI and NBI was performed for each SDL. Endoscopic diagnosis of SDLs was made by each method on site. MAIN OUTCOME MEASUREMENTS The diagnostic accuracy and the time required for diagnosis. RESULTS The diagnostic accuracy was significantly higher for NBI than for WLI (79% vs 44%; P = .0001), as was its sensitivity (70% vs 33%; P = .0005). The diagnostic specificity of NBI (89%) was higher than that of WLI (67%), but the difference was not statistically significant. The time required for the diagnosis was equivalent with both methods. LIMITATIONS Single-center study, small sample size. CONCLUSIONS Adding NBI to the WLI examination is essential for making an accurate diagnosis of gastric SDLs compared with magnifying WLI alone. (UMIN Clinical Trials Registry identification number C000000421).

Efficacy of preventive endoscopic balloon dilation for esophageal stricture after endoscopic resection

Background and Aim We earlier reported that mucosal defect involving over three-fourths of the circumference of the esophagus after endoscopic mucosal resection (EMR) is a risk factor for the development of the stricture. Although endoscopic balloon dilation (EBD) is a useful procedure to relieve the stricture, there is no standard strategy for preventing development of the stricture. The aim of this study was to evaluate the efficacy and the safety of preventive EBD. Methods From 1993 to 2008, 41 consecutive patients with extensive mucosal defect involving over three-fourths of the esophageal circumference after EMR or endoscopic submucosal dissection (ESD) were investigated. Preventive EBD was carried out for 29 cases within 1 week just after EMR/ESD and was repeated once a week until the mucosal defect was completely healed. The remaining 12 cases were not underwent preventive EBD and used as a historic control. If postEMR/ESD stricture developed regardless of preventive EBD, conventional EBD was given repeatedly until the stricture was completely relieved. Results Preventive EBD decreased the incidence of stricture (59% vs. 92%, P =0.04), reduced the severity of stricture [(⩽2 mm; >2 mm and ⩽5 mm; >5 mm)=(1; 2; 14) vs. (4; 4; 3), P = 0.01] and shortened the duration required for resolving the stricture (29 d vs. 78 d, P =0.04) even when stricture developed. There was no complication associated with preventive EBD procedure. Conclusions Preventive EBD is an effective procedure to prevent postEMR/ESD stricture. Preventive EBD should be considered when EMR/ESD results in a mucosal defect with a circumference greater than three-fourths of the esophageal lumen.

Improving visualization techniques by narrow band imaging and magnification endoscopy

Endoscopy plays an important role in the early detection of gastrointestinal tract neoplasms. Using conventional white light or dye‐based image enhanced endoscopy, it has been difficult to assess pre‐malignant and early neoplastic lesions precisely. However, narrow band imaging (NBI) dramatically improves the detection of these lesions, particularly in combination with magnifying endoscopy. This allows the endoscopist to accomplish accurate diagnosis. Such enhanced detection of pre‐malignant and early neoplastic lesions in the gastrointestinal tract should allow better targeting of biopsy, improved and more appropriate treatment, and thereby contribute to optimal quality of life and patient survival.

Long-term outcome of transoral organ-preserving pharyngeal endoscopic resection for superficial pharyngeal cancer.

BACKGROUND Early detection of pharyngeal cancer has been difficult. We reported that narrow-band imaging (NBI) endoscopy can detect superficial pharyngeal cancer, and these lesions can be treated endoscopically. OBJECTIVE To assess the safety and long-term efficacy of transoral organ-preserving pharyngeal endoscopic resection (TOPER) for superficial pharyngeal cancer. DESIGN AND SETTING Retrospective 2-center cohort study. PATIENTS The study included 104 consecutive patients with superficial pharyngeal cancer. INTERVENTION TOPER with the patients under general anesthesia. MAIN OUTCOME MEASUREMENTS Safety of the procedure, long-term survival, clinical outcome. RESULTS A total of 148 consecutive lesions were resected in 104 patients. There was no severe adverse event. Temporary tracheostomy was required in 17 patients (16%) to prevent airway obstruction. The median fasting period and hospital stay after TOPER were 2 days (range 1-20 days) and 8 days (range 3-58 days), respectively. Ninety-six patients (92%) had no local recurrence or distant metastases. Local recurrence at the primary site developed in 6 patients, but all were resolved by repeat TOPER. With a median follow-up period of 43 months (range 3-96 months), the overall survival rate at 5 years was 71% (95% CI, 59-82). Cause-specific survival rate at 5 years was 97% (95% CI, 93-100). The cumulative development rate of multiple cancers in pharyngeal mucosal sites at 5 years was 22% (95% CI, 12-33). The pharynx was preserved in all patients, and they experienced no loss of function. LIMITATION Retrospective design. CONCLUSIONS Peroral endoscopic resection of superficial pharyngeal cancer is a feasible and effective treatment with curative intent.

Narrow-band imaging of the gastrointestinal tract

A narrow-band imaging (NBI) system is now commercially available worldwide from Olympus Medical Systems as an endoscopic diagnostic tool for the gastrointestinal (GI) tract. The most important strengths of the NBI system are enhancements in endoscopic visualization of superfi cial neoplastic lesions and the microvascular architecture. As endoscopic magnifi cation maximizes the latter strength, NBI is expected to yield breakthroughs in endoscopic diagnosis. Angiogenesis is critical in the transition from the premalignant to the malignant phenotype, so detection and diagnosis based in part on morphologic changes to the microvessels are ideal. These advantages will potentially allow us to easily identify and accurately diagnose superfi cial neoplasms of the GI tract. In contrast, conventional endoscopic diagnosis using white light is based on subtle morphological changes such as superfi cially elevated, fl at, or depressed lesions and on minimal changes in color such as reddish discoloration. However, these fi ndings are diffi cult to recognize, especially for inexperienced endoscopists, who require much skill training. As a result, the diagnosis may be inaccurate or a precancerous lesion or superfi cial cancer in the GI tract may be overlooked. From the point of view of the effective cancer screening, these disadvantages must be overcome. When combined with magnifying endoscopy, NBI can clearly demarcate the margin between a nonneoplastic lesion and a cancerous lesion and can increase the contrast of morphological changes of the mucosal surface and microvessels. Inoue and colleagues and Yao and colleagues have already reported the importance of fi ndings of microvascular irregularities in cancer of the esophagus and stomach, respectively. However, in images magnifi ed while using white light, these changes have been diffi cult to identify. With NBI, these changes are easily recognized, thus renewing our awareness of the importance of microvascular irregularities in cancerous lesions. Herein, we review publications on use of an NBI system in the GI tract.

Phase I study of photodynamic therapy using talaporfin sodium and diode laser for local failure after chemoradiotherapy for esophageal cancer

BackgroundPhotodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, however it causes a high rate of skin phototoxicity and requires a long sun shade period. Talaporfin sodium is a rapidly cleared photosensitizer that is expected to have less phototoxicity. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT) for esophageal cancer.MethodsThis phase I, laser dose escalation study used a fixed dose (40 mg/m2) of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy). The primary endpoint was to assess the dose limiting toxicity (DLT) of PDT, and the secondary endpoints were to evaluate the adverse events and toxicity related to PDT. The starting fluence of the 664 nm diode laser was 50 J/cm2, with an escalation plan to 75 J/cm2 and 100 J/cm2.Results9 patients with local failure after CRT or RT for ESCC were enrolled and treated in groups of 3 individuals to the third fluence level. No DLT was observed at any fluence level. Phototoxicity was not observed, but one subject had grade 1 fever, three had grade 1 esophageal pain, and 1 had grade 1 dysphagia. Five of 9 patients (55.6%) achieved a complete response after PDT.ConclusionsPDT using talaporfin sodium and a diode laser was safe for local failure after RT in patients with esophageal cancer. The recommended fluence for the following phase II study is 100 J/cm2.

Usefulness of endoscopic radial incision and cutting method for refractory esophagogastric anastomotic stricture (with video).

BACKGROUND There is no effective treatment for gastroesophageal anastomotic strictures that are refractory to repeated endoscopic balloon dilation (EBD). However, EBD is still selected worldwide to manage such refractory strictures. To relieve the symptoms of dysphagia and keep a wide lumen, we developed a new incisional treatment, radial incision and cutting (RIC). OBJECTIVE To evaluate the efficacy and safety of the RIC method for the treatment of refractory anastomotic strictures. DESIGN Retrospective cohort study. SETTING National Cancer Center and University Hospital. PATIENTS This study involved 54 consecutive patients with refractory anastomotic stricture after esophagogastric surgery. INTERVENTION RIC. MAIN OUTCOME MEASUREMENTS The safety and clinical success of RIC and the long-term patency after RIC compared with those of continued EBD. RESULTS The median procedure time of RIC was 14 minutes (range, 4-40 minutes). No serious adverse events associated with RIC were observed. Immediately after RIC, 81.3% (26/32) of patients were able to eat solid food without symptoms of dysphagia. As a short-term effect, the dysphagia improved after RIC in 93.8% (30/32) of the patients. As a long-term effect, 63% (17/27) and 62% (13/21) of patients were able to eat solid food 6 and 12 months after RIC, respectively. The 6-month and 12-month patency rates were significantly different between the RIC group and the continued EBD group (65.3% vs 19.8%, P < .005; 61.5% vs 19.8%, P < .005). LIMITATIONS Nonrandomized retrospective study. CONCLUSIONS RIC is an effective and safe method. The demonstration of the validity of this method may place RIC as a new medical treatment for patients with refractory stricture after surgical resection for esophagogastric diseases.

An efficient diagnostic strategy for small, depressed early gastric cancer with magnifying narrow-band imaging: a post-hoc analysis of a prospective randomized controlled trial

BACKGROUND We previously reported that magnifying narrow-band imaging (M-NBI) is a high-performance diagnostic tool for small, depressed gastric cancer. However, an efficient diagnostic strategy using endoscopic findings has not been fully elucidated. OBJECTIVE To identify the endoscopic findings that contribute to accurate diagnosis of small, depressed gastric cancer and to propose the ideal diagnostic approach to such lesions. DESIGN Post-hoc analysis of a prospective, randomized, controlled trial. SETTING Nine hospitals. PATIENTS Three hundred fifty-three patients with small, depressed gastric lesions. INTERVENTIONS In the M-NBI group (n = 177), cancer diagnosis was made with diagnostic criteria including a demarcation line (DL) and an irregular microvascular pattern (IMVP). In the conventional white-light imaging (C-WLI) group (n = 176), diagnostic criteria were both an irregular margin and a spiny depressed area. In the C-WLI group, M-NBI was performed after C-WLI diagnosis. MAIN OUTCOME MEASUREMENTS The diagnostic performance of each criterion in M-NBI alone, C-WLI, and M-NBI after C-WLI was investigated. RESULTS M-NBI after C-WLI ultimately showed the best diagnostic performance in each diagnostic criterion. In M-NBI after C-WLI, evaluation of DL is technically easier than that of IMVP, and DL alone had a high sensitivity (95%) and negative predictive value (99%). The IMVP in M-NBI after C-WLI had a high sensitivity and specificity (95% and 96%, respectively) for diagnosis of cancer. LIMITATIONS Lesions were limited to the small, depressed type. CONCLUSIONS For a diagnosis using M-NBI after C-WLI, identification of DL is the first step, and subsequent inspection of IMVP diagnosed by DL is an efficient strategy.

Tissue Damage in the Canine Normal Esophagus by Photoactivation with Talaporfin Sodium (Laserphyrin): A Preclinical Study

Background Treatment failure at the primary site after chemoradiotherapy is a major problem in achieving a complete response. Photodynamic therapy (PDT) with porfimer sodium (Photofrin®) has some problems such as the requirement for shielding from light for several weeks and a high incidence of skin phototoxicity. PDT with talaporfin sodium (Laserphyrin) is less toxic and is expected to have a better effect compared with Photofrin PDT. However, Laserphyrin PDT is not approved for use in the esophagus. In this preclinical study, we investigated tissue damage of the canine normal esophagus caused by photoactivation with Laserphyrin. Methodology/Principal Findings Diode laser irradiation was performed at 60 min after administration. An area 5 cm oral to the esophagogastric junction was irradiated at 25 J/cm2, 50 J/cm2, and 100 J/cm2 using a three-step escalation. The irradiated areas were evaluated endoscopically on postirradiation days 1 and 7, and were subjected to histological examination after autopsy. The areas injured by photoactivation were 52 mm2, 498 mm2, and 831 mm2 after irradiation at 25 J/cm2, 50 J/cm2, and 100 J/cm2, respectively. Tissue injury was observed in the muscle layer or even deeper at any irradiation level and became more severe as the irradiation dose increased. At 100 J/cm2 both inflammatory changes and necrosis were seen histologically in extra-adventitial tissue. Conclusions/Significance To minimize injury of the normal esophagus by photoactivation with Laserphyrin, diode laser irradiation at 25 J/cm2 appears to be safe. For human application, it would be desirable to investigate the optimal laser dose starting from this level.