Ikuo Aoyama

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.

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.

A Phase III study of oral steroid administration versus local steroid injection therapy for the prevention of esophageal stricture after endoscopic submucosal dissection (JCOG1217, Steroid EESD P3)

A randomized Phase III trial commenced in Japan in September 2014. Endoscopic local steroid injection has been commonly used and considered acceptable as the current standard treatment for the prevention of esophageal stricture after endoscopic submucosal dissection for superficial esophageal cancer. The purpose of this study is to confirm the superiority of prophylactic oral steroid administration following endoscopic submucosal dissection in terms of stricture-free survival over endoscopic local steroid injection for patients with superficial esophageal cancer. A total of 360 patients will be accrued from 35 Japanese institutions within 2.5 years. The primary endpoint is stricture-free survival, and the secondary endpoints are the number of endoscopic balloon dilations for 12 weeks after endoscopic submucosal dissection, adverse events, serious adverse events and the proportion of patients with dysphagia score ≤1 at 12 weeks after endoscopic submucosal dissection. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015064 (http://www.umin.ac.jp/ctr/index.htm).

A randomized controlled Phase II/III study comparing endoscopic balloon dilation combined with steroid injection versus radial incision and cutting combined with steroid injection for refractory anastomotic stricture after esophagectomy: Japan Clinical Oncology Group Study JCOG1207

A randomized Phase II/III trial commenced in May 2014. Endoscopic balloon dilation with steroid injection is the current standard treatment for patients with refractory anastomotic stricture after esophagectomy. The purpose of this study is to confirm the superiority of radial incision and cutting with steroid injection in terms of both restricture-free survival and number of dilations within 24 weeks compared with endoscopic balloon dilation with steroid injection for these patients. A total of 130 patients will be accrued from 30 Japanese institutions over 3 years. The primary endpoint in the Phase II part is proportion of Grade 3/4 intraoperative hemorrhages, post-operative esophageal perforations, esophageal hemorrhages, pneumothorax, lung or mediastinum infections or other unexpected adverse events. Co-primary endpoints in the Phase III part are restricture-free survival and number of dilations within 24 weeks after treatment. Secondary endpoints are proportion of patients with anastomotic diameter >10 mm at 8 weeks after treatment, proportion of adverse events, proportion of patients experiencing improvement of dysphagia score at 2, 4, 8 and 24 weeks after treatment and proportion of patients with dysphagia score ≤1 at 24 weeks after treatment. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000014017 [http://www.umin.ac.jp/ctr/index.htm].

Establishment of a Quick and Highly Accurate Breath Test for ALDH2 Genotyping

OBJECTIVES: Acetaldehyde, the first metabolite of ethanol, is a definite carcinogen for the esophagus, head, and neck; and aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that catalyzes the metabolism of acetaldehyde. The ALDH2 genotype exists as ALDH2*1/*1 (active ALDH2), ALDH2*1/*2 (heterozygous inactive ALDH2), and ALDH2*2/*2 (homozygous inactive ALDH2). Many epidemiological studies have reported that ALDH2*2 carriers are at high risk for esophageal or head and neck squamous cell carcinomas by habitual drinking. Therefore, identification of ALDH2*2 carriers would be helpful for the prevention of those cancers, but there have been no methods suitable for mass screening to identify these individuals. METHODS: One hundred and eleven healthy volunteers (ALDH2*1/*1 carriers: 53; ALDH2*1/*2 carriers: 48; and ALDH2*2/*2 carriers: 10) were recruited. Breath samples were collected after drinking 100 ml of 0.5% ethanol using specially designed gas bags, and breath ethanol and acetaldehyde levels were measured by semiconductor gas chromatography. RESULTS: The median (range) breath acetaldehyde levels at 1 min after alcohol ingestion were 96.1 (18.1–399.0) parts per billion (p.p.b.) for the ALDH2*1/*1 genotype, 333.5 (78.4–1218.4) p.p.b. for the ALDH2*1/*2 genotype, and 537.1 (213.2–1353.8) p.p.b. for the ALDH2*2/*2 genotype. The breath acetaldehyde levels in ALDH2*2 carriers were significantly higher than for the ALDH2*1/*1 genotype. Notably, the ratio of breath acetaldehyde level‐to‐breath ethanol level could identify carriers of the ALDH2*2 allele very accurately (whole accuracy; 96.4%). CONCLUSIONS: Our novel breath test is a useful tool for identifying ALDH2*2 carriers, who are at high risk for esophageal and head and neck cancers.

Paraneoplastic Limbic Encephalitis in a Human Epidermal Growth Factor Receptor-2-positive Gastric Cancer Patient Treated with Trastuzumab-combined Chemotherapy: A Case Report and Literature Review.

Paraneoplastic neurological syndromes (PNSs) are rare nervous system dysfunctions in cancer patients, which are primarily observed with small-cell lung cancer, gynecological cancer, and thymoma. We herein present an uncommon case of PNS in an anti-Hu antibody-positive patient with human epidermal growth factor receptor (HER)-2-positive gastric cancer (GC), who developed limbic encephalitis and a worsening cognitive function. Trastuzumab-combined chemotherapy was initiated and appeared to be partially effective for controlling the neurological symptoms and tumor volume. Chemotherapy failure eventually led to uncontrollable neurological symptoms. This is the first case demonstrating that trastuzumab-combined chemotherapy may be effective for controlling neurological symptoms of PNS in HER2-positive GC patients.

S-1 Salvage Chemotherapy for Esophageal Squamous Cell CarcinomaRefractory to the Standard Chemotherapy

Objective: Fluorouracil, cisplatin, and taxane are widely used in the standard chemotherapy regimens for esophageal squamous cell carcinoma (ESCC). Although S-1 is expected to demonstrate considerable efficacy for ESCC, there is any clinical data. The purpose of this retrospective study was to evaluate the efficacy and safety of S-1 as salvage chemotherapy for ESCC. Methods: From 2007 to 2014, fifteen patients with ESCC refractory or refusal to the standard chemotherapy were treated with S-1 as salvage treatment at the Kyoto University Hospital and their clinical records were reviewed retrospectively. Results: The median age was 70 years old (range: 63-77). A complete response (CR) was achieved in 1 case (7%). A stable disease (SD) and progressive disease (PD) were seen in 9 (60%) and 5 (33%) cases, respectively. After a follow-up duration of 13.9 months, median progression free survival and overall survival was 6.2 and 10.0 months, respectively. One-year survival rate was 33.3%. Toxicities greater than CTCAE grade 3 were observed in 3 of 15 patients (20%). Two patients had grade 3 neutropenia and one patient had grade 3 diarrhea. There was no treatment related death. Conclusions: S-1 salvage chemotherapy could be expected to be an effective and safe treatment option to improve the prognosis of patients with ESCC refractory to the standard chemotherapy.

Successful conservative management of diffuse cavernous hemangioma of the rectum

Diffuse cavernous hemangioma of the rectum (DCHR) is a relatively rare disease. A 40-year-old man presented with long-standing lower abdominal discomfort and hematuria. At the time of hospitalization, his vital signs and hemoglobin level were normal. Colonoscopy showed markedly dilated blood vessels in the sigmoid mucosa, which was confirmed on magnetic resonance imaging and computed tomography as cavernous hemangioma. Without surgery, there have been no signs of progression of DCHR during a 3-year follow-up period.