Shuko Morita

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.

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.

Bile acid-induced expression of activation-induced cytidine deaminase during the development of Barrett’s oesophageal adenocarcinoma

Activation-induced cytidine deaminase (AID) induces somatic mutations in various host genes of non-lymphoid tissues, thereby contributing to carcinogenesis. We recently demonstrated that Helicobacter pylori infection and/or proinflammatory cytokine stimulation triggers aberrant AID expression in gastric epithelial cells, causing mutations in the tumour-suppressor TP53 gene. The findings of the present study provide evidence of ectopic AID expression in Barretts oesophagus and Barretts oesophageal adenocarcinoma, a cancer that develops under chronic inflammatory conditions. Immunoreactivity for endogenous AID was observed in 24 of 28 (85.7%) specimens of the columnar cell-lined Barretts oesophagus and in 20 of 22 (90.9%) of Barretts adenocarcinoma, whereas weak or no AID protein expression was detectable in normal squamous epithelial cells of the oesophagus. We validated these results by analysing tissue specimens from another cohort comprising 16 cases with Barretts oesophagus and four cases with Barretts adenocarcinoma. In vitro treatment of human non-neoplastic oesophageal squamous-derived cells with sodium salt deoxycholic acid induced ectopic AID expression via the nuclear factor-kappaB activation pathway. These findings suggest that aberrant AID expression occurs in a substantial proportion of Barretts epithelium, at least in part due to bile acid stimulation. Considering the genotoxic activity of AID, our current findings suggest that aberrant AID expression might enhance the susceptibility to genetic alterations in Barretts columnar-lined epithelial cells, leading to cancer development.

Transoral surgery for laryngo-pharyngeal cancer – The paradigm shift of the head and cancer treatment

Transoral surgery is a less invasive treatment that is becoming a major strategy in the treatment of laryngo-pharyngeal cancer. It is a minimally invasive approach that has no skin incision and limits the extent of tissue dissection, disruption of speech and swallowing muscles, blood loss, damage to major neurovascular structures, and injury to normal tissue. Transoral approaches to the laryngo-pharynx, except for early glottis cancer, had been limited traditionally to tumors that can be observed directly and manipulated with standard instrumentation and lighting. Since the 1990s, transoral laser microsurgery (TLM) has been used as an organ preservation strategy with good oncological control and good functional results, although it has not been widely used because of its technical difficulty. Recently, transoral robotic surgery (TORS) is becoming popular as a new treatment modality for laryngo-pharyngeal cancer, and surgical robots are used widely in the world since United States FDA approval in 2009. In spite of the global spread of TORS, it has not been approved by the Japan FDA, which has led to the development of other low-cost transoral surgical techniques in Japan. Transoral videolaryngoscopic surgery (TOVS) was developed as a new transoral surgery system for laryngo-pharyngeal lesions to address the problems of TLM. In TOVS, a rigid endoscope is used to visualize the surgical field instead of a microscope and the advantages of TOVS include the wide operative field and working space achieved using the distending laryngoscope and videolaryngoscope. Also, with the spread of narrow band imaging (NBI), endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), which are widely used for superficial cancers in the gastrointestinal tract, have been applied for the superficial laryngo-pharyngeal cancer. Both EMR and ESD are performed mainly by gastroenterologists with a sharp dissector and magnifying endoscopy (ME)-NBI with minimal surgical margin. Endoscopic laryngo-pharyngeal surgery (ELPS) was developed to treat laryngo-pharyngeal superficial cancer by modifying the ESD procedure. The concept of ELPS is the same as that of ESD, however, the resection procedure is performed by a head and neck surgeon with both hands using a ME-NBI and rigid curved laryngo-pharyngoscope. These four procedures are low cost with similar oncological and functional outcomes to TORS. TORS may be less expensive than chemoradiotherapy, but the number of hospitals that can afford da Vinci surgical systems is limited. Even in the era of robotic surgery, these four procedures will be good options for laryngo-pharyngeal cancer.

Magnifying Endoscopy with Narrow Band Imaging to Determine the Extent of Resection in Transoral Robotic Surgery of Oropharyngeal Cancer

Transoral robotic surgery (TORS) is a less invasive treatment that is becoming popular all over the world. One of the most important factors for achieving success in TORS is the ability to determine the extent of resection during the procedure as the extent of resection in the laryngopharynx not only affects oncological outcomes but also directly affects swallowing and voice functions. Magnifying endoscopy with narrow band imaging (ME-NBI) is an innovative optical technology that provides high-resolution images and is useful in detecting early superficial pharyngeal cancers, which are difficult to detect by standard endoscopy. A 55-year-old male with superficial oropharyngeal cancer has been successfully treated by combining MB-NBI with TORS and MB-NBI was useful in determining the extent of resection. ME-NBI with TORS will make it possible to achieve a higher ratio of minimally invasive treatment in pharyngeal cancer.

Magnifying endoscope with NBI to predict the depth of invasion in laryngo-pharyngeal cancer

To examine if macroscopic classification with a magnifying gastrointestinal endoscope with narrow band imaging (ME‐NBI) is useful in predicting pathological depth of tumor invasion in laryngo‐pharyngeal cancer.

Clinical outcome after endoscopic resection for superficial pharyngeal squamous cell carcinoma invading the subepithelial layer.

BACKGROUND AND STUDY AIMS The curability of endoscopic resection for superficial pharyngeal squamous cell carcinoma (SPSCC) has not been fully elucidated, particularly for lesions invading the subepithelial layer, which carry the risk of metastasis. The aim of this study was to evaluate the curative potential of endoscopic resection for SPSCC invading the subepithelial layer. PATIENTS AND METHODS From June 2002 to July 2010, 198 SPSCCs in 176 consecutive patients were treated by endoscopic resection at two tertiary referral centers. Selection criteria were initial endoscopic resection, histologically proven squamous cell carcinoma invading the subepithelial layer, no lymph node or distant metastasis before endoscopic resection, and no prior treatment for pharyngeal squamous cell carcinoma. Endoscopic resection was performed under general anesthesia. Long-term survival and clinical outcomes were retrospectively evaluated. RESULTS Among 176 consecutive patients, 50 lesions in 47 patients (all male; median age 64 years) were histologically diagnosed from endoscopic resection specimens as having subepithelial invasion. Median tumor thickness was 1000 μm (range 200 - 10 000 μm). Six patients developed local recurrence (13 %; 95 % confidence interval [CI] 3.1 % - 22.4 %), and all were cured with organ-preserving intervention. After a median follow-up period of 71 months (range 27 - 116 months), one patient (2 %; 95 %CI 0 - 6.3 %) developed neck lymph node metastasis. A total of 14 patients (30 %) were followed for 5 years or more, and 5-year overall survival and disease-specific survival rates were 84.5 % (95 %CI 73 % - 96 %) and 100 %, respectively. CONCLUSIONS Endoscopic resection has curative potential as a minimally invasive treatment option for SPSCC that invades the subepithelial layer.