Waku Hatta

Optical coherence tomography for the staging of tumor infiltration in superficial esophageal squamous cell carcinoma.

BACKGROUND Optical coherence tomography (OCT) is a noninvasive technology that can produce high-resolution cross-sectional images in real-time without acoustic coupling, enabling precise assessment of tumor invasion in superficial esophageal squamous cell carcinomas (SESCCs). OBJECTIVE To elucidate the usefulness of in vivo OCT for the staging of SESCCs. DESIGN A single-center, prospective study in 2 phases: phase I to establish the OCT criteria classified into 3 categories (epithelium or lamina propria mucosa [EP/LPM], muscularis mucosa [MM], submucosa [SM]) and phase II to evaluate these criteria. SETTING An academic medical center. PATIENTS Sixty-two patients with a histological diagnosis of SESCC by routine endoscopy. In the phase I study, 35 images from 16 patients were used. In the phase II study, 109 images from 46 subsequent consecutive patients enrolled from January 2007 to May 2009 were used. INTERVENTIONS We performed OCT for preoperative staging followed by endoscopic submucosal dissection or a surgical procedure and compared precisely the visualized OCT sites with the corresponding tissue sections. MAIN OUTCOME MEASUREMENTS The accuracy of OCT for the staging. RESULTS The overall accuracy rate was 92.7% (EP/LPM, 94.9%; MM, 85.0%; SM, 90.9%). The OCT signal penetration depth was sufficient to depict the boundary of the deepest region of cancer, the thickness of which was less than 1.5 mm. LIMITATIONS The small number of patients. CONCLUSIONS To our knowledge, this is the first study demonstrating that OCT might be useful for the preoperative staging of SESCCs with a high degree of accuracy.

A prospective comparative study of optical coherence tomography and EUS for tumor staging of superficial esophageal squamous cell carcinoma

BACKGROUND The precise assessment of superficial esophageal squamous cell carcinomas (SESCCs) limited to the epithelium (EP) or lamina propria mucosa (LPM), the standard indication for endoscopic resection, is important to ensure good outcomes of endoscopic resection. With regard to tomographic imaging techniques, although the accuracy of EUS is practically insufficient, we previously demonstrated that high-resolution optical coherence tomography (OCT) might enable precise assessment for staging in a noninvasive and real-time manner. OBJECTIVE To clarify the accuracy of the preoperative staging of SESCCs by using OCT compared with that by using 20-MHz probe-type EUS. DESIGN A prospective study. SETTING An academic medical center. PATIENTS A total of 123 consecutive patients with 131 SESCCs were enrolled from May 2007 to September 2011. INTERVENTIONS A specialist examined the patients, by using both OCT and EUS, recorded a representative still image for each lesion, and reported the staging immediately after each examination. Another blinded investigator reviewed the recorded images and reported the staging independently. The histological staging was confirmed by the resected specimens. Finally, we calculated the accuracy of staging by using OCT and EUS. MAIN OUTCOME MEASUREMENTS The accuracy of OCT or EUS for EP/LPM. RESULT The accuracy for EP/LPM by using OCT was significantly higher than that by using EUS (OCT, 94.6%; HF-EUS, 80.6%; P < .05). Interobserver agreement of OCT and EUS was good and moderate, respectively. LIMITATIONS The small number of patients; a single-center, single-operator, nonrandomized, crossover study. CONCLUSIONS We prospectively demonstrated that the preoperative staging of SESCC by using OCT was more useful than that by using EUS.

A Scoring System to Stratify Curability after Endoscopic Submucosal Dissection for Early Gastric Cancer: "eCura system".

Objectives:Although radical surgery is recommended for patients not meeting the curative criteria for endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) because of the potential risk of lymph node metastasis (LNM), this recommendation may be overestimated and excessive. We aimed to establish a simple scoring system for decision making after ESD.Methods:This multicenter retrospective study consisted of two stages. First, the risk-scoring system for LNM was developed using multivariate logistic regression analysis in 1,101 patients who underwent radical surgery after having failed to meet the curative criteria for ESD of EGC. Next, the system was internally validated by survival analysis in another 905 patients who also did not meet the criteria and did not receive additional treatment after ESD.Results:In the development stage, based on accordant regression coefficients, five risk factors for LNM were weighted with point values: three points for lymphatic invasion and 1 point each for tumor size >30 mm, positive vertical margin, venous invasion, and submucosal invasion ≥500 μm. Then, the patients were categorized into three LNM risk groups: low (0–1 point: 2.5% risk), intermediate (2–4 points: 6.7%), and high (5–7 points: 22.7%). In the validation stage, cancer-specific survival differed significantly among these groups (99.6, 96.0, and 90.1%, respectively, at 5 years; P<0.001). The C statistic of the system for cancer-specific mortality was 0.78.Conclusions:This scoring system predicted cancer-specific survival in patients who did not meet the curative criteria after ESD for EGC. ESD without additional treatment may be an acceptable option for patients at low risk.

Comparison of the Long-Term Outcomes of Endoscopic Resection for Superficial Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus in Japan

OBJECTIVES:Few studies have simultaneously evaluated the long-term outcomes of endoscopic resection (ER) for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus in Japan. The objective of this study was to evaluate the long-term outcomes of ER for superficial esophageal cancer in consecutive patients.METHODS:This was a retrospective study from a single institution. From April 2001 to June 2012, 204 patients with SCC and 26 patients with AC were included from a total of 355 consecutive patients who were treated by esophageal ER at the Tohoku University Hospital. Patients with submucosal invasion deeper than 200 μm and lymphovascular involvement were excluded. The intervention followed was endoscopic therapy.RESULTS:Overall survival, disease-free survival, and recurrence rates were evaluated as long-term outcomes. In the SCC group, during the median observation time of 36.5 months (range, 6–120 months), 22 (10.8%) patients experienced metachronous recurrence, 4 (2.0%) patients experienced local recurrence, and 27 (13.2%) patients died from causes unrelated to SCC. In the AC group, during the median observation time of 45.5 months (range, 6–131 months), one patient (3.8%) experienced metachronous recurrence and two (7.7%) died from causes unrelated to AC. The cumulative 5-year overall survival rates were not significantly different between SCC (75.9%) and AC (88.9%) (P=0.120). The cumulative 5-year disease-free survival rates of SCC (57.1%) were significantly lower than those of AC (85.2%; P=0.017). The cumulative 5-year recurrence rates of SCC (32.0%) were significantly higher than those of AC (4.2%; P=0.023).CONCLUSIONS:The rate of recurrence after ER was higher in patients with SCC than that in patients with AC. These findings suggest that, by detecting AC of the esophagus earlier, a satisfactory prognosis without recurrence can be expected after ER in Japan, and more rigorous endoscopic follow-up is necessary after ER in patients with SCC than in those with AC.

Effects of ALDH2 Genotype, PPI Treatment and L-Cysteine on Carcinogenic Acetaldehyde in Gastric Juice and Saliva after Intragastric Alcohol Administration

Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30–50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups.

Direct Measurement of Gastroesophageal Reflux Episodes in Patients With Squamous Cell Carcinoma by 24-h pH-Impedance Monitoring

OBJECTIVES:Recent studies have consistently reported a significant association between gastric atrophy and esophageal squamous cell carcinomas (ESCCs). However, causative factors responsible for the linkage remain to be clarified. Multichannel intraluminal impedance monitoring in conjunction with a pH sensor (MII-pH) is a reliable technique to evaluate gastroesophageal reflux (GER) episodes, independent of the acidity. We investigated the potential roles of GER in the pathogenesis of ESCC with MII-pH.METHODS:From August 2008 to May 2010, 14 consecutive inpatients with superficial ESCCs (ESCC group) and 14 age- and sex-matched inpatients without any esophageal dysplastic lesions (non-ESCC group) were enrolled. Twenty-four hour portable MII-pH monitoring was performed under standard hospitalized conditions. The data of MII-pH were used to identify acid reflux (AR: pH drop below 4.0 during a reflux episode) and non-AR (NAR: pH drop above 4.0 during a reflux episode).RESULTS:The median intragastric pH of the ESCC group was 4.7 (2.3–6.4), implying hypochlorhydria in this patient group. The numbers of total reflux and NAR episodes in the ESCC group were significantly higher than those in the non-ESCC group (56 (43–87) vs. 35.5 (18–47), P=0.016 for total reflux and 46.5 (32–84) vs. 24.5 (8–37), P=0.012 for NAR), whereas the numbers of AR were similar in both groups. In addition, there was significance in the category of percentage time of bolus reflux episodes.CONCLUSIONS:Using MII-pH monitoring, we revealed the clinical significance of GER, especially NAR, in ESCCs. NAR may be a key factor in the link between gastric atrophy and ESCCs.

Estrogen Enhances Esophageal Barrier Function by Potentiating Occludin Expression.

BackgroundWe recently demonstrated that a female sex hormone, estrogen, suppressed esophageal epithelial injury in a reflux esophagitis model of rat, suggesting that estrogen may play an important role in controlling the progress of the gastro-esophageal reflux disease spectrum. However, the precise mechanism of the action is unclear.AimTo investigate the potential role of estrogen in the esophageal barrier function.MethodsMale rabbits were pretreated with either continuous release 17β-estradiol or placebo, and the excised esophageal mucosa was subjected to Ussing chamber experiments after the 2-week pre-treatment. The mucosal side of the chamber was perfused with luminal irritants (HCl or acidified sodium nitrite), while the basal side was perfused by modified Krebs buffer. The epithelial barrier function was evaluated by the transmembrane resistance and the epithelial permeability. The intercellular space of the epithelium was investigated with transmission electron microscopy and the expression of tight junction protein, occludin, claudin-1, and claudin-4, with immunoblotting.ResultsEstrogen pre-treatment significantly attenuated the decrease in the transmembrane resistance and the increase in the epithelial permeability induced by luminal irritants. Furthermore, the dilation of the intercellular space induced by luminal HCl was significantly alleviated by 17β-estradiol administration. The baseline occludin expression was significantly potentiated by 17β-estradiol administration.ConclusionsThis is the first study showing an enhancement of the esophageal barrier function by 17β-estradiol administration. The lack of the protective effect of estrogen could be responsible for the male predominance of erosive reflux esophagitis.

Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan

In Japan, after the revision of the gastrointestinal endoscopic guidelines for patients taking antithrombotics, endoscopic biopsies were permitted while continuing antithrombotic treatment. However, the risk of bleeding after the biopsy with or without cessation of antithrombotics has not been fully evaluated because bleeding events are very rare. The aim of this prospective study was to evaluate the risk for bleeding after upper gastrointestinal biopsy without cessation of antithrombotics.

Feasibility of optical coherence tomography for the evaluation of Barrett's mucosa buried underneath esophageal squamous epithelium

Evaluation of Barretts glands buried underneath esophageal squamous epithelium becomes increasingly important in order to achieve curative treatment. However, clinically available endoscopes have critical limitations in depicting subsurface structure, resulting in non‐curative treatment. Optical coherence tomography (OCT) can achieve a high‐resolution cross‐sectional image, equivalent to an optical biopsy. We aimed to assess the feasibility of in vivo use of probe‐type OCT imaging to evaluate Barretts mucosa buried underneath esophageal squamous epithelium.

Endoscopic findings for predicting gastric acid secretion status.

Gastric acidic abnormalities are related to various types of diseases in Helicobacter pylori (H. pylori) infection status. However, no studies have shown correlations between many tiny endoscopic findings and the acid secretion level simultaneously. In the present study, we investigated predictive tiny endoscopic findings of hyperchlorhydria and hypochlorhydria.