Induction of PIR-A/B+ DCs in the in vitro inflammatory condition and their immunoregulatory function.

BACKGROUND: Dendritic cells (DCs), primary antigen-presenting cells, are now well known as an immunoregulator of many aspects of immune responses including inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis. We have reported that PIR-A/Bhigh cDCs (conventional DCs) appeared in dextran sodium sulfate (DSS)-induced colitis and serve as a negative immunoregulator in an animal model of IBD. The immunoregulatory role of PIR-A/B+ cDCs was confirmed in both an in vitro culture system and an in vivo transfer experiment. Here, we have investigated the differentiation process of PIR-A/B+ cDCs in an in vitro inflammatory environment and examined their functions. METHODS: cDCs were isolated from the large intestinal lamina propria from C57BL/6 mice and cultured in an inflammatory environment (IL-1, IL-6, TNFα, and LPS). The appearance of PIR-A/B+ cDCs was determined after 24 h, and the in vitro-induced PIR-A/B+ cDCs were functionally and genetically examined. RESULTS: PIR-A/B+ cDCs were detected after a 24-h culture only in the inflammatory environment, and the cells acted as a negative immunoregulator when examined in an allogenic mixed leukocyte reaction (MLR). The message level of IL-27 was highly upregulated in PIR-A/B+ cDCs, while that of high mobility group box 1 protein (HMGB1) was downregulated in these cells. This was well in accordance with the fact that PIR-A/B+ cDCs showed a suppressive function against activated T cells. We found that PIR-A/B+ cDCs produced IL-27, as verified by an ELISA assay, and that the inhibitory effect by PIR-A/B+ cDCs was, at least partially, due to IL-27. Furthermore, CD85d+ cells, a human counterpart of mouse PIR-A/B+ cDCs, were found in the lamina propria of the colon of the patients with ulcerative colitis, but not in the similar part of the non-inflammatory area of colon specimens from patients with colon cancer. CONCLUSIONS: PIR-A/B+ cDCs induced in an in vitro inflammatory environment model showed a suppressive function against activated T cells by producing an inhibitory cytokine.

Incomplete resection rate of cold snare polypectomy: a prospective single-arm observational study.

Background and study aims Cold snare polypectomy (CSP) is considered to be safe for the removal of subcentimeter colorectal polyps. This study aimed to determine the rate of incomplete CSP resection for subcentimeter neoplastic polyps at our center. Patients and methods Patients with small or diminutive adenomas (diameter 1 - 9 mm) were recruited to undergo CSP until no polyp was visible. After CSP, a 1 - 3 mm margin around the resection site was removed using endoscopic mucosal resection. The polyps and resection site marginal specimens were microscopically evaluated. Incomplete resection was defined as the presence of neoplastic tissue in the marginal specimen. We also calculated the frequency at which the polyp lateral margins could be assessed for completeness of resection. Results A total of 307 subcentimeter neoplastic polyps were removed from 120 patients. The incomplete resection rate was 3.9 % (95 % confidence interval [CI] 1.7 % - 6.1 %); incomplete resection was not associated with polyp size, location, morphology, or operator experience. The polyp lateral margins could not be assessed adequately for 206 polyps (67.1 %). Interobserver agreement between incomplete resection and lateral polyp margins that were inadequate for assessment was poor (κ = 0.029, 95 %CI 0 - 0.04). Female sex was an independent risk factor for incomplete resection (odds ratio 4.41, 95 %CI 1.26 - 15.48; P  = 0.02). Conclusions At our center, CSP resection was associated with a moderate rate of incomplete resection, which was not associated with polyp characteristics. However, adequate evaluation of resection may not be routinely possible using the lateral margin from subcentimeter polyps that were removed using CSP.Trial registered at University Hospital Medical Information Network (UMIN 000010879).

A comparative study of grasping-type scissors forceps and insulated-tip knife for endoscopic submucosal dissection of early gastric cancer: a randomized controlled trial.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is technically difficult for beginners. Few comparative studies of technical feasibility, efficacy, and safety using various devices have been reported. This study evaluated the feasibility, efficacy, and safety of ESD for EGC < 2 cm using grasping-type scissors forceps (GSF) or insulated-tip knife (IT2) for three resident endoscopists. PATIENTS AND METHODS: This was a randomized phase II study in a cancer referral center. A total of 108 patients with 120 EGCs were enrolled with the following characteristics: differentiated-type mucosal EGC, without ulcers or scars, < 2 cm (86 men, 22 women; median age 72 years). All lesions were stratified according to operator and tumor location (antrum or corpus), assigned randomly to two groups (GSF or IT2), and resected by ESD. Self-completion rate, complete resection rate, procedure time, and adverse events were evaluated as main outcome measures. RESULTS: There was no difference in self-completion rate between the IT2 group (77 %, 47/61, P = 0.187) and the GSF group (66 %, 37/56). Also, there were no differences in en bloc resection rate (98 %, 60/61 vs. 93 %, 52/56, P = 0.195) and adverse events (3.3 %, 2/61 vs. 7.1 %, 4/56, P = 0.424). Median (min [range]) procedure time in the IT2 group (47 [33 - 67], P = 0.003) was shorter than that in the GSF group (66 [40 - 100]). Limitations of this study were the small sample size and single center design. CONCLUSIONS: ESD with GSF did not show a statistically significant advantage in improvement of self-completion rate over IT2. ( STUDY REGISTRATION: UMIN 000005048).

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 requiring endoscopic 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.

Diagnostic features of sessile serrated adenoma/polyps on magnifying narrow band imaging: a prospective study of diagnostic accuracy.

BACKGROUND AND AIMS: The narrow band imaging classification system (NBI International Colorectal Endoscopic [NICE] classification) classifies colorectal polyps very accurately. However, sessile serrated adenoma/polyps (SSA/Ps) pathologically resembles hyperplastic polyp and has a possibility to be left in situ on NICE classification. The aim of this study was to establish and evaluate new simple diagnostic features for SSA/Ps using magnifying narrow band imaging (M-NBI). METHODS: We performed a single-arm observational study of diagnostic accuracy in two stages, as follows: seeking stage, development of simple diagnostic features for SSA/P and definition of diagnostic criteria based on retrospective assessments of M-NBI; and validation stage, prospective validation and evaluation of the new diagnostic criteria. RESULTS: In the seeking stage, we identified brownish, oval, expanded crypt openings and thick-branched vessels on the surfaces of SSA/Ps. We named these "expanded crypt openings" (ECOs) and "thick and branched vessels" (TBVs), respectively. In the validation stage, we enrolled 796 polyps in 261 patients, and classified 126 polyps as NICE type 1; all these lesions were endoscopically removed and assessed histopathologically. The sensitivity, specificity, and accuracy of ECOs for SSA/Ps were 84.3%, 81.1%, and 82.4%, whereas those of TBVs were 45.1%, 68.9%, and 59.2%, respectively. M-NBI provided a sensitivity of 98% and specificity of 59.5% for discrimination of SSA/Ps from other lesions classified as NICE type 1. CONCLUSIONS: Identification of ECOs, supplemented with TBVs, has high sensitivity for the diagnosis of SSA/P. These findings may facilitate the use of endoscopic optical diagnosis in clinical practice.

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 pink-color 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 pink-color 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.

Randomized study of two endo-knives for endoscopic submucosal dissection of esophageal cancer.

OBJECTIVES: Settings for endoscopic submucosal dissection (ESD) of esophageal cancer have not been standardized, and no studies have directly compared ESD devices in humans. METHODS: We conducted a randomized study to compare the performances of two different endo-knives, the Flush knife and Mucosectom, for esophageal ESD in 48 lesions. All procedures were initiated by two endoscopists, who were assisted by senior endoscopists with verbal advice. In the Flush-knife group, mucosal incision with a 2-mm Flush knife was followed by submucosal dissection using a 1-mm Flush knife. In the Mucosectom group, mucosal incision with a 2-mm Flush knife was followed by submucosal dissection with a Mucosectom. The primary outcome variable was the procedure time required for submucosal dissection. The secondary outcome variables were total procedure time, self-completion rates, and adverse events. RESULTS: Total procedure time in the Mucosectom group was significantly shorter than in the Flush-knife group (57±21 vs. 83±27 min, respectively; P<0.001). The submucosal-dissection time in the Mucosectom group was significantly shorter than in the Flush-knife group (40±18 vs. 61±23 min, respectively; P<0.001). The self-completion rate in the Mucosectom group was slightly higher than in the Flush-knife group, but the difference was not significant (91.7% vs. 75%, respectively; P=0.25). One perforation and one postoperative bleeding occurred in the Flush-knife group, both of which were treated successfully by endoscopic treatment. CONCLUSIONS: The Mucosectom reduced the procedure and submucosal-dissection times of esophageal ESD, without increasing adverse events.

Usefulness of chromoendoscopy and magnifying narrow band imaging endoscopy for diagnosis of demarcation of adenocarcinoma in Barrett's esophagus.

It is often difficult to accurately delineate the borders and extent of early-stage esophageal adenocarcinoma in patients with Barrett's esophagus using conventional white light endoscopy. Chromoendoscopy enhances the characteristics of the mucosa and improves detection and delineation of small or flat lesions difficult to identify by conventional endoscopy. Magnifying endoscopy with narrow-band imaging (NBI) is a novel endoscopic imaging technology that contrasts the vascular architecture and surface structure of the superficial mucosa. As magnifying NBI can view only a narrow area of the mucosa, this method cannot determine the circumference of the lesion and evaluate its complete extent. Indigocarmine chromoendoscopy is useful for delineating the extent of Barrett's adenocarcinoma. Chromoendoscopy and magnifying NBI are complementary methods, with both being required for the accurate diagnosis of tumor extent in patients with superficial Barrett's esophageal adenocarcinoma.

Long-term outcome and metastatic risk after endoscopic resection of superficial esophageal squamous cell carcinoma.

OBJECTIVES: Long-term outcomes after endoscopic resection (ER) provide important information for the treatment of esophageal carcinoma. This study aimed to investigate the rates of survival and metastasis after ER of esophageal carcinoma. METHODS: From 1995 to 2010, 570 patients with esophageal carcinoma were treated by ER. Of these, the 402 patients with squamous cell carcinoma (280 epithelial (EP) or lamina propria (LPM) cancer, 70 muscularis mucosa (MM) cancer, and 52 submucosal (SM) cancer) were included in our analysis. Seventeen patients had cancer invading into the submucosa up to 0.2 mm (SM1) and 35 patients had cancer invading into the submucosa more than 0.2 mm (SM2). RESULTS: The mean (range) follow-up time was 50 (4-187) months. The 5-year overall survival rates of patients with EP/LPM, MM, and SM cancer were 90.5, 71.1, and 70.8%, respectively (P=0.007). Multivariate analysis identified depth of invasion and age as independent predictors of survival, with hazard ratios of 3.6 for MM cancer and 3.2 for SM cancer compared with EP/LPM cancer, and 1.07 per year of age. The cumulative 5-year metastasis rates in patients with EP/LPM, MM, SM1, and SM2 cancer were 0.4, 8.7, 7.7, and 36.2%, respectively (P<0.001). Multivariate analysis identified depth of invasion as an independent risk factor for metastasis, with hazard ratios of 13.1 for MM, 40.2 for SM1, and 196.3 for SM2 cancer compared with EP/LPM cancer. The cumulative 5-year metastasis rates in patients with mucosal cancer with and without lymphovascular involvement were 46.7 and 0.7%, respectively (P<0.0001). CONCLUSIONS: The long-term risk of metastasis after ER was mainly associated with the depth of invasion. This risk should be taken into account when considering the indications for ER.

Clinical outcomes of endoscopic mucosal resection and endoscopic submucosal dissection as a transoral treatment for superficial pharyngeal cancer.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been introduced for the treatment of superficial pharyngeal cancer. METHODS: Sixty superficial pharyngeal cancers in 45 patients were treated by EMR or ESD. Resectability and curability, complications, and survival were analyzed retrospectively. RESULTS: The en bloc resection and curative resection rate were higher with ESD (100; 81.6%) than with EMR (59; 50%). In subgroup analysis with regard to tumor size ≤ 10 mm, both resection rates were comparative. All the patients had preserved larynx and swallowing, speech, and airway function. Two of the 45 patients died of other diseases, local recurrence was observed in 4 of 18 patients with noncurative resection with a median observation period of 38 months. No recurrence was observed in patients with curative resection. CONCLUSIONS: ESD or EMR for superficial pharyngeal cancer is minimally invasive treatment and lesions larger than 10 mm should be referred for ESD.

Histological features responsible for brownish epithelium in squamous neoplasia of the esophagus by narrow band imaging.

BACKGROUND AND AIM: Esophageal squamous neoplasias usually appear brown under narrow band imaging as a result of microvascular proliferation, and brownish color changes in the areas between vessels, referred to as brownish epithelium. However, the reasons for the development of this brownish epithelium and its clinical implications have not been fully investigated. METHODS: Patients with superficial esophageal neoplasias treated by endoscopic resection were included in the study. Areas of mucosa with brownish and non-brownish epithelia were evaluated histologically. RESULTS: A total of 68 superficial esophageal neoplasias in 58 patients were included in the analysis. Of the 68 lesions, 32 were classified in the brownish epithelium group, and 36 in the non-brownish epithelium group. Brownish epithelium was significantly associated with a diagnosis of high-grade intraepithelial neoplasia or invasive cancer (P < 0.0001). Thinning of the keratinous layer, thinning of the epithelium, and cellular atypia were significantly associated with brownish epithelium by univariate analysis, and thinning of the keratinous layer and thinning of the epithelium were confirmed to be independent factors by multivariate analysis. The odds ratios were 9.6 (95% confidence interval: 2.0-46.3) for thinning of the keratinous layer, and 4.6 (95% confidence interval: 1.1-19.4) for thinning of the epithelium. CONCLUSIONS: Brownish epithelium is an important finding in the diagnosis of esophageal squamous neoplasia, and may be related to thinning of the keratinous layer, caused by neoplastic cell proliferation, and thinning of the epithelium.

Safety and curative ability of endoscopic submucosal dissection for superficial esophageal cancers at least 50 mm in diameter.

BACKGROUND AND AIM: Limited data are available regarding the use of endoscopic submucosal dissection (ESD) for superficial esophageal cancers ≥ 50 mm in diameter. The aim of the present study was to investigate the safety and success of ESD for superficial esophageal cancers ≥ 50 mm. METHODS: A total of 39 patients with superficial esophageal squamous cell carcinoma ≥ 50 mm were treated with ESD at Osaka Medical Center for Cancer and Cardiovascular Diseases between January 2004 and April 2011, and were analyzed in a retrospective study. RESULTS: En bloc resection was achieved in all patients. One mediastinal emphysema without perforation occurred during the procedure. Stricture developed in 11 of 39 patients, requiring a median of five endoscopic balloon dilatation procedures. Thirty-three clinical epithelial or lamina propria mucosal cancers were treated by ESD with curative intent, of which invasion into the muscularis mucosa or deeper was detected in seven and lymphovascular involvement in three. The en bloc resection rate was 100% with a tumor-free margin achieved in 92% of lesions. The curative resection and complication rates during ESD were 70% and 2.5%, respectively. CONCLUSION: ESD achieved a high en bloc resection rate of 92% with a tumor-free margin. Curative resection rate of ESD in patients with clinical epithelial or lamina propria mucosal cancers was not low at 70%. However, the risk of stricture must be taken into account when considering the use of ESD in lesions ≥ 50 mm.

Factors predicting perforation during endoscopic submucosal dissection for gastric cancer.

BACKGROUND: Perforation is a common complication of endoscopic submucosal dissection (ESD), but little is known about the relevant risk factors. OBJECTIVE: To investigate the risk factors for perforation. DESIGN: Retrospective study. SETTING: A cancer referral center. PATIENTS: A total of 1795 early gastric tumors in 1500 patients treated by ESD from July 2002 to December 2010 were included in the analysis. MAIN OUTCOME MEASUREMENTS: The associations between the incidence of perforation and patient and lesion characteristics were investigated. RESULTS: Perforation during ESD occurred in 50 lesions (2.8%). Univariate analysis identified tumor location (upper, middle, or lower stomach), tumor diameter (≤ 20 or >20 mm), and treatment period (lesions treated in the first or second period) as predictors of perforation. Multivariate analysis identified tumor location (upper stomach), tumor diameter (>20 mm), and treatment period (first half) as independent risk factors for perforation. The odds ratios were 2.4 (95% CI, 1.3-4.7; P = .006) for lesions in the upper stomach and 1.9 (95% CI, 1.0-3.5; P = .04) for lesions larger than 20 mm. Perforation risks were 5.4% for lesions in the upper stomach and 4.4% for lesions larger than 20 mm. Three patients required emergency surgery, but the rest of the patients were successfully treated with endoscopic clipping. There was no perforation-related mortality. LIMITATIONS: Single-center, retrospective study design. CONCLUSIONS: Lesions in the upper stomach and lesions larger than 20 mm were independent risk factors for perforation during ESD. Patients should be made aware of the estimated high risks of these lesions before undergoing ESD.

Comprehensive investigation of areae gastricae pattern in gastric corpus using magnifying narrow band imaging endoscopy in patients with chronic atrophic fundic gastritis.

BACKGROUND: Barium radiographic studies have suggested the importance of evaluating areae gastricae pattern for the diagnosis of gastritis. Significance of endoscopic appearance of areae gastricae in the diagnosis of chronic atrophic fundic gastritis (CAFG) was investigated by image-enhanced endoscopy. MATERIALS AND METHODS: Endoscopic images of the corpus lesser curvature were studied in 50 patients with CAFG. Extent of CAFG was evaluated with autofluorescence imaging endoscopy. The areae gastricae pattern was evaluated with 0.2% indigo carmine chromoendoscopy. Micro-mucosal structure was examined with magnifying chromoendoscopy and narrow band imaging. RESULTS: In patients with small extent of CAFG, polygonal areae gastricae separated by a narrow intervening part of areae gastricae was observed, whereas in patients with wide extent of CAFG, the size of the areae gastricae decreased and the width of the intervening part of areae gastricae increased (p < 0.001). Most areae gastricae showed a foveola-type micro-mucosal structure (82.7%), while intervening part of areae gastricae had a groove-type structure (98.0%, p < 0.001). Groove-type mucosa had a higher grade of atrophy (p < 0.001) and intestinal metaplasia (p < 0.001) compared with foveola type. CONCLUSIONS: As extent of CAFG widened, multifocal groove-type mucosa that had high-grade atrophy and intestinal metaplasia developed among areae gastricae and increased along the intervening part of areae gastricae. Our observations facilitate our understanding of the development and progression of CAFG.

Indication, strategy and outcomes of endoscopic submucosal dissection for colorectal neoplasm.

Although endoscopic submucosal dissection (ESD) for colorectal neoplasm is a promising endoscopic therapy with a high rate of successful en bloc resection, ESD for colorectal neoplasm is not a health-care service provided by Japanese public heath insurance, yet. Now, ESD for colorectal neoplasm has been approved as an 'advanced medical treatment' system, which is a partial-care service provided by Japanese public health insurance with individual payment of medical expenses, and the indication for ESD for colorectal neoplasm has been under debate. In our hospital, a total of 348 colorectal neoplasms underwent ESD using the FlexKnife and the FlushKnife, and 317 lesions (91%) were resected en bloc. Perforation occurred in eight cases (2%) and they were not critical and did not require emergent surgery. Delayed bleeding occurred in 16 cases (4%) and they were able to be controlled without transfusion and were not critical. The major impact of the advanced medical treatment system on clinical practice in our hospital was the increased incidence of adenocarcinoma and increased tumor size in the lesions that underwent ESD. It is thought that the application of the advanced medical treatment system resulted in careful selection of lesions for ESD while maintaining the principle of en bloc resection. We expect that a new, revised indication that covers recurrent carcinoma after endoscopic therapy will be indicated when ESD for colorectal neoplasm becomes a health-care service provided by Japanese public health insurance.

Autofluorescence imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia: a phase II study.

BACKGROUND AND AIM: Few prospective studies examining the efficacy of autofluorescence imaging (AFI) screening for esophageal cancer have been reported. This study aimed to investigate the diagnostic value of AFI endoscopy for the screening of squamous mucosal high-grade neoplasia of the esophagus, performed by experienced and less-experienced endoscopists. METHODS: Patients with a history of esophageal neoplasia or head and neck cancer underwent AFI endoscopic screening, followed by chromoendoscopy using iodine staining as the reference standard. The primary outcome was the sensitivity of AFI for detecting new squamous mucosal high-grade neoplasias. The secondary outcome was the positive predictive value (PPV) of AFI. RESULTS: Of a total 364 patients who underwent endoscopic examination, 43 new mucosal high-grade neoplasias were detected. The sensitivities of AFI in the experienced and less-experienced endoscopist groups were 71% (95% confidence interval [CI]: 55-87%) and 50% (95% CI: 32-68%), respectively. The PPV of AFI in the experienced and the less-experienced endoscopist groups were 25% (95% CI: 16-34%) and 26% (95% CI: 15-37%), respectively. The sensitivity of AFI in lesions ≤ 10 mm (31%, 5/16 lesions) was significantly lower than that in lesions > 10 mm (78%, 21/27 lesions) (P = 0.003). CONCLUSIONS: The sensitivity of AFI for the detection of new squamous mucosal high-grade neoplasias, and its PPV, were both low. Based on these results, a randomized study to compare AFI with standard techniques is not justified.

Construction and analysis of self-cloning sake yeasts that accumulate proline.

We constructed self-cloning diploid sake yeast strains that accumulate proline. The appropriate proline level is important for its protective effect against ethanol stress in yeast cells. Sake brewed with the proline-accumulating strains contained two- to threefold more proline than the sake brewed with the parent strain. It was also suggested that intracellular proline does not affect overall fermentation profiles, but reduces fermentation time in terms of ethanol production rate.