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Endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) cases. Additional esophagectomy or chemoradiotherapy is recommended for non-curative resection (NCR) even with pathologically negative vertical margins (pVM0); however, their clinical outcomes remain unknown. We examined the long-term clinical outcomes of NCR for ESCCs according to additional treatments.We retrospectively analyzed the data of patients who underwent ER for cT1N0M0 ESCC between 2009 and 2017 judged to have NCR, which defined when pathologically diagnosed as invading the submucosa (SM) or muscularis mucosae (MM) involving lymphovascular invasion (LVI), pVM0, and endoscopically judged as negative horizontal margin. Additional esophagectomy (involving three-field lymphadenectomy), chemoradiotherapy [mainly cisplatin and 5-fluorouracil with concurrent radiotherapy (41.4 Gy)], or observation was undertaken. Thereafter, computed tomography was performed every 6-12 months. The cumulative recurrence (CRR) and recurrence-free survival (RFS) rates were evaluated.Eighty-nine patients were included. Among them, 14 had pathologically diagnosed pMM with LVI; 9 and 6, and 32 and 28 patients had pSM1 and pSM2 without and with LVI. Twenty-one patients underwent observation, whereas 18 and 50 underwent esophagectomy and chemoradiotherapy. During the 60.6-month median follow-up period, nine patients had recurrence; among them, six patients had occurrence at 4 years after ER. The 5-year CRR/RFS rates were 35.7%/48.1%, 13.4%/80.4%, and 0.0%/98.0% in the observation, esophagectomy, and chemoradiotherapy groups, respectively (observation vs. chemoradiotherapy; P 0.001).Additional treatments showed better long-term outcomes than observation for patients with NCR. As recurrence may occur at 4 years after ER, careful long-term follow-up examinations are needed.

OBJECTIVES Photodynamic therapy (PDT) is an optional salvage treatment for local failure of esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy; however, local failure after PDT sometimes occurs. In such cases, second PDT is sometimes attempted, but its outcomes remain unclear. This study aimed to evaluate the efficacy and safety of second PDT. METHODS We enrolled patients who underwent PDT for local failure of ESCC after chemoradiotherapy. We retrospectively evaluated local-complete response (L-CR) rate and clinical outcomes of first and second PDT. The indications for PDT were lesions within the muscle layer

Background and study aims The Japan Narrow-band imaging (NBI) Expert Team (JNET) classification was proposed for evaluating colorectal lesions. However, it remains unknown whether the JNET classification can be applied to magnifying endoscopy with image-enhanced endoscopies other than NBI. This study aimed to compare the diagnostic ability of JNET classification by magnifying endoscopy with blue laser imaging (ME-BLI) and with ME-NBI. Patients and methods We retrospectively assessed consecutive patients diagnosed per the JNET classification by ME-BLI (BLI group) or ME-NBI (NBI group) between March 2014 and June 2017. We compared the diagnostic value of JNET classification between the groups with one-to-one propensity score matching. Results Four hundred and seventy-one propensity score-matched pairs of lesions were analyzed. In the BLI and NBI groups, the overall diagnostic accuracies were 92.1 % and 91.7 %, respectively, and those for differentiating between neoplastic and non-neoplastic polyps were 96.6 % and 96.8 %, respectively. The positive predictive value by each JNET classification in BLI vs. NBI group was 90.6 % vs. 96.2 % in Type 1, 94.3 % vs. 94.6 % in Type 2A, 57.7 % vs. 42.3 % in Type 2B, and 100 % vs. 91.7 % in Type 3. The negative predictive value was 97.0 % vs. 96.9 % in Type 1, 88.1 % vs. 82.8 % in Type 2A, 98.0 % vs. 98.2 % in Type 2B, and 98.5 % vs. 98.7 % in Type 3. No statistical difference in the diagnostic results was found between the groups. Conclusions The diagnostic ability of the JNET classification by ME-BLI and ME-NBI was comparable, with the former also applicable for diagnosis of colorectal lesions.

Endoscopic submucosal dissection (ESD) is the standard treatment for cT1a esophageal squamous cell carcinoma (ESCC), however its indication for the entire circumferential lesions is still controversial because of the risk of severe stricture after ESD. Therefore, several treatment options are performed based on physicians’ choice, however, each clinical course is unclear. This study aimed to clarify the long-term outcome after ESD for patients with entire circumferential cT1aN0M0 ESCC, comparing with esophagectomy or chemoradiotherapy. Methods Patients with entire circumferential cT1aN0M0 SESCC treated with ESD, chemoradiotherapy, or esophagectomy as the initial treatment between January 2010 and December 2016 in our institution were included. Patients who had a history of any malignancy at cStage II-IV within 5 years were excluded. The 5-year overall survival (OS), 5-year disease-free survival (DFS), stricture rate, refractory stricture rate (defined as requiring >6 dilations), curative resection (defined as pT1a without lymphovascular invasion and negative for vertical margin in the pathological evaluation) rate of ESD, and complete response rate of chemoradiotherapy were evaluated for each treatment. Results Of the 48 eligible patients, 25/13/10 patients were performed ESD/chemoradiotherapy/esophagectomy as an initial treatment. Curative resections rate of ESD was 72%, and additional esophagectomy and chemoradiotherapy were performed in three and one patients with non-curative resection. Complete response rate of chemoradiotherapy was 100%, however, 4 patients had recurrence thereafter. No recurrences occurred after esophagectomy in all patients treated with esophagectomy. During median follow-up of 83 months, stricture and refractory stricture rate was 80/44% after ESD, 0/0% after chemoradiotherapy, and 20/10% after esophagectomy. The 5-year OS/DFS was 91/87% after ESD, 92/59% after chemoradiotherapy, and 90/90% after esophagectomy. Conclusion While some patients required additional treatments due to non-curative resection, the long-term survival after ESD for circumferential cT1aN0M0 ESCC was similar as those after chemoradiotherapy or esophagectomy. In contrast, the stricture and refractory stricture rate after ESD was higher than others. Further investigation in a large cohort is necessary to clarify the indication criteria of ESD for patients with the lesion.

The diagnosis of gastrointestinal stromal tumor (GIST) using conventional endoscopy is difficult because submucosal tumor (SMT) lesions like GIST are covered by a mucosal layer. Near-infrared hyperspectral imaging (NIR-HSI) can obtain optical information from deep inside tissues. However, far less progress has been made in the development of techniques for distinguishing deep lesions like GIST. This study aimed to investigate whether NIR-HSI is suitable for distinguishing deep SMT lesions. In this study, 12 gastric GIST lesions were surgically resected and imaged with an NIR hyperspectral camera from the aspect of the mucosal surface. Thus, the images were obtained ex-vivo. The site of the GIST was defined by a pathologist using the NIR image to prepare training data for normal and GIST regions. A machine learning algorithm, support vector machine, was then used to predict normal and GIST regions. Results were displayed using color-coded regions. Although 7 specimens had a mucosal layer (thickness 0.4-2.5 mm) covering the GIST lesion, NIR-HSI analysis by machine learning showed normal and GIST regions as color-coded areas. The specificity, sensitivity, and accuracy of the results were 73.0%, 91.3%, and 86.1%, respectively. The study suggests that NIR-HSI analysis may potentially help distinguish deep lesions.

BACKGROUND AND AIM To assess the visibility of colorectal lesions using blue laser imaging (BLI)-bright and linked-color imaging (LCI) with an eye-tracking system. METHODS Eleven endoscopists evaluated 90 images of 30 colorectal lesions. The lesions were randomly selected. Three images of each lesion comprised white light imaging (WLI), BLI-bright, and LCI in the same position. Participants gazed at the images, and their eye movements were tracked by the eye tracker. We analyzed whether the participants could detect the lesion and how long they took to detect the lesion. We assessed the miss rate and detection time among the imaging modalities. RESULTS One endoscopist was excluded, and 10 endoscopists were assessed. Overall, 12.6% of lesions were missed with WLI, 6.0% with BLI-bright, and 4.3% with LCI; the miss rate of BLI-bright and LCI was significantly lower than that of WLI (P

The diagnosis of gastrointestinal stromal tumor (GIST) using conventional endoscopy is difficult because submucosal tumor (SMT) lesions like GIST are covered by a mucosal layer. Near-infrared hyperspectral imaging (NIR-HSI) can obtain optical information from deep inside tissues. However, far less progress has been made in the development of techniques for distinguishing deep lesions like GIST. This study aimed to investigate whether NIR-HSI is suitable for distinguishing deep SMT lesions. In this study, 12 gastric GIST lesions were surgically resected and imaged with an NIR hyperspectral camera from the aspect of the mucosal surface. Thus, the images were obtained ex-vivo. The site of the GIST was defined by a pathologist using the NIR image to prepare training data for normal and GIST regions. A machine learning algorithm, support vector machine, was then used to predict normal and GIST regions. Results were displayed using color-coded regions. Although 7 specimens had a mucosal layer (thickness 0.4–2.5 mm) covering the GIST lesion, NIR-HSI analysis by machine learning showed normal and GIST regions as color-coded areas. The specificity, sensitivity, and accuracy of the results were 73.0%, 91.3%, and 86.1%, respectively. The study suggests that NIR-HSI analysis may potentially help distinguish deep lesions.

Gastric cancer is the most frequent primary cancer-associated with esophageal cancer and is most commonly detected by endoscopic surveillance. However, the clinical features of synchronous or metachronous gastric cancer that could be detected by esophagogastroduodenoscopy in esophageal cancer patients are unknown. We reviewed the clinical records of all esophageal cancer patients (n = 1379) registered in the cancer registration database who underwent initial treatment between April 2010 and October 2015. We retrospectively analyzed the proportions of synchronous and metachronous gastric cancer cases, the cumulative incidence rate of metachronous gastric cancer in total and by esophageal cancer treatments (endoscopic resection, esophagectomy, and chemoradiotherapy), and the clinical features of esophageal cancer patients with synchronous or metachronous gastric cancer. Overall, 67 (5.3% of 1275) esophageal cancer patients with synchronous gastric cancer and 40 (5.1% of 791) esophageal cancer patients with metachronous gastric cancer were analyzed. The 5-year cumulative incidence rate of metachronous gastric cancer was 5.6% in total, 7.8% after endoscopic resection, 4.7% after esophagectomy, and 4.1% after chemoradiotherapy for esophageal cancer. From the results of multivariate analysis, the risk factors for synchronous gastric cancer were male (odds ratio 13.3) and moderate/severe atrophic gastritis (odds ratio 17.9), and the risk factor of metachronous gastric cancer was moderate/severe atrophic gastritis (hazard ratio 27.6) in patients with esophageal cancer. The incidence rates of synchronous and metachronous gastric cancer with esophageal cancer were both over 5%. Careful endoscopic observation is required for moderate and severe atrophic gastritis at detecting concomitant gastric cancer in esophageal cancer patients.

Background and Aims Lymph node recurrence (LNR) after endoscopic resection (ER) in patients with esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (pMM) without lymphovascular invasion (LVI) has been reported as non-negligible in the ER guidelines for esophageal cancer by the Japan Gastroenterological Endoscopy Society. However, these data were not regarded as high-level evidence because several retrospective case series were tabulated without sufficient long-term follow-up. Hence, this guideline stated that the administration of additional treatment after ER could not be determined for this population. This study aimed to clarify the long-term clinical outcomes after ER of pMM ESCC without LVI. Methods Between January 2009 and November 2017, we enrolled followed-up patients who underwent ER and were pathologically diagnosed with pMM ESCC without LVI without additional treatments. We retrospectively investigated the cumulative recurrence rate and recurrence-free, overall, and disease-specific survival at 5 years after ER. Results Eighty-seven patients were enrolled. During the median follow-up period of 64 months (range: 12–117), 3 patients developed lymph node and/or distant recurrence, and 2 of these cases occurred more than 3 years after ER; all 3 patients died of the primary disease. The 5-year cumulative recurrence rate was 4.3%, and the 5-year recurrence-free, disease-specific, and overall survival rates were 88.8%, 98.2%, and 91.7%, respectively. Conclusions The long-term outcome for patients with pMM ESCC without LVI was favorable after ER; however, this population had a risk of recurrence directly leading to death. Long-term follow-up is necessary, with attention to the timing of recurrence.

The purpose of this paper is to evaluate stiffness of a base-isolation layer and a super-structure of high-rise seismic isolated building from the earthquake response observation records with different amplitude levels. As a result, the stiffness of the base-isolation layer based on observation records was close to the design value. As the amplitude increased, the stiffness of the super-structure reduced – confirming the amplitude dependence of the super-structure.

Background and study aims Visual assessment of laterally spreading tumors non-granular type (LST-NG) and depressed lesions by narrow band imaging (NBI) without magnification has not been studied. We investigated the role of non-magnifying NBI in detecting LST-NG and type IIc lesions on colonoscopy. Patients and methods This retrospective study examined consecutive patients diagnosed as having LST-NG and/or type IIc lesions in our hospital between August 2011 and July 2013. These lesions were classified as “Brownish area (BA),” “Brown only in the margins (O-ring sign),” “Same color as the normal mucosa (SC),” and “Whitish area (WA)” based on their appearance on non-magnifying NBI, and their appearance were compared with their histopathological findings. Results A total of 18 type IIc and 180 LST-NG lesions were analyzed. Among the type IIc lesions, 5 (28 %), 12 (67 %), and 1 (5 %) were classified as BA, O-ring sign, and SC, respectively. Among the LST-NG lesions, 126 (70 %), 26 (14 %), and 28 lesions (16 %) were classified as BA, O-ring sign, and SC, respectively. The IIc lesions were found to have 1 lesion (20 %) with high-grade dysplasia (HGD) in the BA, and 2 lesions (17 %) with invasive cancer (IC) in the O-ring sign group. Among the LST-NG lesions, 27 (21 %) were found to have IC and 49 (39 %), HGD in the BA group; 8 lesions (31 %) had IC and 4 (15 %) had HGD in the O-ring sign group; and 1 lesion (4 %) had IC and 4 (14 %) had HGD in the SC group. Conclusions Most flat and depressed colorectal lesions were seen on non-magnifying NBI as brown lesions with the exception of some flat lesions that were indistinguishable in color from the adjacent normal mucosa. Some of these flat lesions were also found to have HGD or IC.

Proton beam therapy (PBT) with concurrent chemotherapy is promising for esophageal squamous cell carcinoma (ESCC). The aim of study was to evaluate the outcome of concurrent chemo-proton therapy (CCPT), i.e., PBT with concurrent chemotherapy for cT1 ESCC and the salvage endoscopic therapy for local recurrence. Patients with clinical T1 ESCC who underwent CCPT (60 GyE) between April 2013 and April 2017 at the National Cancer Center Hospital East were investigated. The efficacy of CCPT at the primary site was evaluated via endoscopy; primary complete response (CR) was defined as disappearance of the tumor lesion/ulcer and absence of cancer cells on biopsy. Endoscopic evaluation was performed with the same protocol of conventional chemoradiotherapy. Local recurrence after CCPT was treated with endoscopic resection for cT1a and with esophagectomy or photodynamic therapy for cT1b+. Of the 44 patients (median age, 70 years) that underwent CCPT, 43 patients (98%) achieved primary CR. Among the 44 patients, the 3-year overall survival rate was 95.2%. Five patients (11%) developed local recurrence without regional lymph node or distant metastasis and received endoscopic resection or photodynamic therapy. All five patients were alive with no recurrence after a median 23 months. The results suggest that CCPT is an effective treatment for cT1 ESCC and careful endoscopic follow-up allows preferable local control with salvage endoscopic treatment.

BACKGROUND AND AIM Endoscopic diagnosis of advanced histology in colorectal lesions sized

Linked color imaging (LCI) and blue laser imaging-bright (BLI-b) improve the visibility of gastrointestinal lesions. In this multicenter study, we compared the effects of LCI and BLI-b on the visibility of flat polyps with visibility scores and color difference (CD) values, including fast-withdrawal and large-monitor observation. We recorded 120 videos of 40 consecutive flat polyps (2–20 mm), adenoma, and sessile serrated adenoma and polyp (SSA/P), using white light imaging (WLI), BLI-b, and LCI from July 2017 to December 2017. All videos were evaluated by eight endoscopists according to a published polyp visibility score of 4 (excellent) to 1 (poor). Additionally, 1.5 ×faster and 1.7 ×sized videos were evaluated. Moreover, we calculated the CD values for each polyp in three modes. The mean LCI scores (3.1 ± 0.9) were significantly higher than the WLI scores (2.5 ± 1.0, p

178 Background: Recently, JCOG0502 trial have shown a comparable efficacy with chemoradiotherapy (CRT) and esophagectomy as standard treatment in patients with clinical stage (cStage) I esophageal squamous cell carcinoma (ESCC), showing the standard treatment option of CRT. However, there is few reports for comparison of clinical outcomes with these treatments in real-world. The aim of this study was to clarify the real-world outcomes in cStage I ESCC who performed with CRT or esophagectomy. Methods: This retrospective study included patients with clinical stage I ESCC who received thoracoscopic or open esophagectomy with three-field lymph node dissection or CRT mainly consisted of 5-fluorouracil and platinum with concurrent radiotherapy (50.4 Gy/28Fr or 60 Gy/30Fr) between 2009 and 2017 at National Cancer Center Hospital East. Survival outcomes were calculated using the Kaplan-Meier method, and the differences were evaluated using the log-rank test. Results: Among a total of 156 patients, 128 were male and median age was 68 years old. 120 and 36 patients underwent esophagectomy and CRT, respectively. ECOG performance status 0/1/2 were 138/12/6 patients. Tumor location was Ut/Mt/Lt in 16/87/53 patients. Clinical tumor depth (MM-SM1/SM2-SM3) were 33/123 patients. Patients’ characteristics were similar among treatment groups, except clinical tumor depth (SM2-3; 84.2% in esophagectomy group vs. 61.1% in CRT group, p = 0.005). All patients underwent radical surgery in esophagectomy group, while three patients (8.3%) in CRT group were received additional esophagectomy or endoscopic resection due to residual disease. With a median follow-up of 72 months, 5-year overall survival (OS) and progression-free survival rate were 81.5%/77.0% in esophagectomy group and 82.6/74.4% in CRT group (p = 0.89 and p = 0.48). In safety profile, grade 3 or higher stenosis was observed in 21.7% of esophagectomy group. There was no treatment-related death in both groups. In subgroup analysis for OS, elderly patients (75 years and older) tended to have better 5-year OS rate in CRT group (76.9% in esophagectomy group vs. 81.8% in CRT group), while younger patients ( < 75 years) showed comparable 5-year OS rate in both groups (82.4% in esophagectomy group vs. 82.9% in CRT group). Conclusions: Real-world data reproduced the results of clinical trial, supporting CRT as one of the standard treatment options in patients with cStage I ESCC.

Background To develop a triplet regimen containinggemcitabine,cisplatin,andS-1(GPS),weassessedtherecom-mendeddoseforpatientswithuntreatedadvancedbiliarytractcancer in this phase I study.Methods Dose-limitingtoxicities(DLTs)wereevaluatedforthe following two dose levels: gemcitabine (1000mg/m 2 forlevel 1 and 1200mg/m 2 for level 2 on day 1), cisplatin(30mg/m 2 fixeddoseonday1),andS-1(40–60mg/dayfixeddose twice a day for 7days), every 2weeks until progression.DLTs for each level were evaluated in six or more patientsduring the first twocycles.Results A total of 18 patients were enrolled and 16 patientswere evaluated. DLTs at level 1 were observed in two of10 patients. At level 2, a DLT was observed in one of sixpatients. The main grade 3 or 4 treatment-related adverseevents were neutropenia and leukopenia, and a few non-hematological toxicities were observed. Among 14 patientswith measurable lesions, the best response rate was 50%.Conclusions GPS with a relative dose intensity correspond-ingto90%ofthestandardgemcitabinepluscisplatinregimencould be administered safely, and showed preliminary antitu-mor activity. Survival benefits will be studied subsequently.Keywords Biliary tract cancer · Cholangiocarcinoma ·Cisplatin · Gallbladder carcinoma · Gemcitabine · S-1IntroductionGemcitabine and fluoropyrimidine (FU) are used widely inpatients with advanced biliary tract cancer (ABTC). Re-cently, gemcitabine plus cisplatin (GP) combination che-motherapy has been recognized as a standard first-linechemotherapy based on the results of a phase III study(ABC-02), which compared GP to gemcitabine alone inpatients with ABTC [1]. Since then, FU-containingregimens have been used as second-line chemotherapyfor ABTC. S-1, which contains tegafur, gimeracil, andoteracil, has been approved for the treatment of varioussolid tumors including ABTC in Japan, and S-1 incombination with cisplatin has been approved for gastriccancer therapy in Europe [2]. It showed promisingactivity against ABTC in several studies [3–10] and ismainly used in gemcitabine-refractory patients in Japan.However, all patients do not receive second-line chemo-therapy. The proportion of patients who receivedsecond-line chemotherapy after the failure of first-linechemotherapy was reportedly 20 to 70% [1, 11, 12]. It was60% in our previous study, where we explored prognosticfactors for ABTC [13].This study aimed to develop a triplet regimen, GP plusS-1, using valid drugs in the upfront treatment of patientswith ABTC.

Changes in story stiffness and natural frequency of a high-rise building on the E-defense full-scale shaking test are experimentally evaluated from small excitations to the end of the ultimate shakes, which are expected to employ as damage index for structural health monitoring. Two kinds of changes are observed similarly from both shake test and ambient vibration, which occurred in the first seismic experiences by small excitations and after the severe damage when complete ruptures on main girders appeared in ultimate shakes. The latter severe changes in story stiffness are well-simulated by using a finite element analysis for seismic design.

Millet is an important food crop in Asia and Africa, but the health benefits of dietary millet are little known. This study defined the effects of dietary Japanese millet on diabetic mice. Feeding of a high-fat diet containing Japanese millet protein concentrate (JMP, 20% protein) to type 2 diabetic mice for 3 weeks significantly increased plasma levels of adiponectin and high-density lipoprotein cholesterol (HDL cholesterol) and decreased the levels of glucose and triglyceride as compared to control. The starch fraction of Japanese millet had no effect on glucose or adiponectin levels, but the prolamin fraction beneficially modulated plasma glucose and insulin concentrations as well as adiponectin and tumor necrosis factor-alpha gene expression. Considering the physiological significance of adiponectin and HDL cholesterol levels in type 2 diabetes, insulin resistance, and cardiovascular disease, our findings imply that dietary JMP has the potential to ameliorate these diseases.

We propose a novel stuffed-toy robot with ability to express its intention through different responding force of the arms under force control. The robot is soft enough that people may want to embrace. The core of the research is the new force control mechanism for detection of the external force acting on the arms of the robot. The robot can sense the external force by a specialized force sensor and then change its stiffness with force control to respond to us. Different compliance on the arms can be realized by the change of force control gain.

In this paper, we examined the effects of dietary protein from proso millet on liver injury induced by D-galactosamine or carbon tetrachloride in rats using serum enzyme activities as indices. D-galactosamine- induced elevations of serum activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were significantly suppressed by feeding the diet containing 20% protein of proso millet for 14 days as compared with those of rats fed a 20% casein diet, but not in the case of carbon tetrachloride. The results showed that proso millet protein is effective at lower dietary protein levels than that of dietary gluten reported previously. Therefore, the findings reported here may suggest that proso millet protein is considered to be another preventive food for liver injury.