The safety and feasibility of endoscopic submucosal dissection using a flexible three-dimensional endoscope for early gastric cancer and superficial esophageal cancer: A prospective observational study.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is performed as one of standard treatments for patients with early gastric cancer (EGC) and superficial esophageal squamous cancer (SESCC). A prototype of a flexible endoscope with a 3-D system has been recently developed. This study aimed to investigate the safety and feasibility of ESD using a 3-D flexible endoscope (3-D ESD) for EGC and SESCC. METHODS: This single-center, prospective, observational study enrolled patients who underwent planned 3-D ESD. The clinical outcomes, including the incidence of adverse events and treatment results, were analyzed. Visibility and manipulation during 3-D ESD were evaluated using a visual analog scale (VAS). We also evaluated the effect of the 3-D system on the endoscopist using VAS and the critical flicker fusion frequency (CFFF). RESULTS: We analyzed 47 EGC and 20 SESCC cases. There are no bleeding cases that required transfusion and perforation during 3-D ESD in both EGC and SESCC patients. However, the incidence of delayed bleeding and delayed perforation was 1.5% (one case) each. The mean VAS scores for recognizing the submucosal layer during the submucosal dissection, visual perception of blood vessel, and depth perception were 72.7 ± 22.2, 74.7 ± 21.8, and 78.2 ± 19.9, respectively. In contrast, the mean VAS score for manipulation was 25.4 ± 19.7. Among endoscopists, there was no significant difference in the VAS of eyestrain and headache before and after ESD, and there was no significant difference in the CFFF. CONCLUSION: The safety and feasibility of 3-D ESD for EGC and SESCC are acceptable in both patients and endoscopists.

Tumor response and survival outcomes of salvage concurrent chemoradiotherapy with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy for postoperative locoregional recurrence of esophageal squamous cell carcinoma.

BACKGROUND: Salvage concurrent chemoradiotherapy is effective against locoregional recurrence after curative resection of esophageal squamous cell carcinoma. However, there is no consensus on its application. We investigated the outcomes of salvage concurrent chemoradiotherapy (60 Gy in 30 fractions) with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy. METHODS: We retrospectively investigated the outcomes and prognostic factors in 51 patients with esophageal squamous cell carcinoma treated with salvage concurrent chemoradiotherapy. RESULTS: The median follow-up was 17.5 (range, 2.8-116.1) months. The overall response, complete response, and partial response rates were 74.5%, 49.0%, and 25.5%, respectively. The median progression-free survival was 8.2 months; the 3-year progression-free survival rate was 22.9%. The median overall survival was 23.1 months; the 3-year overall survival rate was 40.7%. Overall survival was significantly longer in patients with a complete response than in those without (median overall survival: not reached vs. 15.3 months); 3-year overall survival rate: 62.5% vs. 20.3% (hazard ratio: 0.222; P < 0.001). Multivariate analysis showed that the independent prognostic factor for overall survival was < 25 mm longest diameter of metastatic lymph nodes (hazard ratio: 3.71). CONCLUSIONS: Salvage concurrent chemoradiotherapy (60 Gy in 30 fractions) with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy was an effective and safe treatment for locoregional recurrence after curative resection of esophageal squamous cell carcinoma, especially in those approaching a complete response. Additionally, a shorter longest diameter of metastatic lymph nodes may be associated with better long-term survival.

Clinical features and risk factors of gastric cancer detected by esophagogastroduodenoscopy in esophageal cancer patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Endoscopic prediction of advanced histology in colorectal lesions sized <10 mm using the Japan Narrow-band imaging Expert Team classification.

BACKGROUND AND AIM: Endoscopic diagnosis of advanced histology in colorectal lesions sized <10 mm is essential for appropriate selection of resection methods. The Japan Narrow-band imaging Expert Team (JNET) classification has been recently validated for the evaluation of colorectal lesions. Our objective was to investigate the diagnostic value of the JNET classification for advanced histology in colorectal lesions sized <10 mm. METHODS: We enrolled 680 patients with 1472 colorectal lesions sized <10 mm diagnosed according to the JNET classification and who subsequently underwent endoscopic or surgical resection between January and December 2017. We retrospectively examined the relationship between the JNET findings and pathological histology. Multivariate analysis was carried out to assess the predictive power of the JNET findings and clinical characteristics of lesions. RESULTS: Advanced histology was present in 29 (2.0%) lesions. Advanced histology was absent in 68 lesions diagnosed as JNET type 1, whereas 1389 lesions diagnosed as JNET type 2A included 19 lesions of advanced histology (1.4%) with high-grade dysplasia alone. Eleven lesions diagnosed as JNET type 2B comprised eight lesions of advanced histology (72.7%) with four high-grade dysplasia and four submucosal invasive cancer, and two lesions diagnosed as JNET type 3 were submucosal invasive cancer. Multivariate analysis showed that JNET type 2B + 3 was a stronger predictive factor for advanced histology than other clinical risk factors. CONCLUSION: Narrow-band imaging with magnification according to the JNET classification may be a useful modality for identification of advanced histology in colorectal lesions sized <10 mm.

Objective evaluation of the visibility of colorectal lesions using eye tracking.

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 < 0.01), with no significant difference between the former modalities (P = 0.54). Mean (± SD) detection times were 1.58 ± 1.60 s for WLI, 1.01 ± 1.21 s for BLI-bright, and 1.10 ± 1.16 s for LCI. Detection time for BLI-bright and LCI was significantly shorter than that for WLI (P < 0.0001), with no significant difference between the former modalities (P = 0.34). Regarding the miss rate and detection time between the expert and the non-experts, there was a significant difference with WLI but not with BLI-bright and LCI. CONCLUSION: Blue laser imaging-bright and LCI improved the detection of colorectal lesions compared with WLI using an eye-tracking system.

Detection of pharyngeal cancer in the overall population undergoing upper GI endoscopy by using narrow-band imaging: a single-center experience, 2009-2012.

BACKGROUND: Nonmagnifying observation by using narrow-band imaging (NBI) is useful for detecting pharyngeal lesions. Magnifying observation by using NBI can distinguish between cancerous and noncancerous lesions and is therefore useful for the early detection of pharyngeal cancer. OBJECTIVE: To evaluate the usefulness of observation of the pharynx by using NBI in the overall population undergoing upper GI endoscopy. DESIGN: Retrospective study. SETTING: Single tertiary referral center. PATIENTS: A total of 11,050 upper GI endoscopies between January 2009 and December 2012. INTERVENTIONS: Observation of the pharynx by using NBI. MAIN OUTCOME MEASURES: The rate of detection of pharyngeal cancer, the rates of detection according to the reason for endoscopy, and the types of cancers detected. RESULTS: Thirty-eight cancerous lesions were detected in 29 patients (0.26%, 29/11,050). The rate of detection of pharyngeal cancer was significantly higher in patients with a history of head and neck cancer (9.7%, 3/31) or a history of esophageal cancer (3.5%, 10/282). In patients undergoing endoscopy for screening, pharyngeal discomfort, and a history of gastric cancer, the rates of detection of pharyngeal cancer were 0.11% (10/8872), 1.1% (3/265), and 0.19% (3/1600), respectively. Two patients (6.9%) were female. One had a history of esophageal cancer, and the other had pharyngeal discomfort. LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Observation of the pharynx by using NBI in patients with previous head and neck cancer or esophageal cancer or who have pharyngeal discomfort is very important. Moreover, pharyngeal cancer was certainly found in the male patients undergoing screening endoscopy, although the rate was lower.

Can flat-type brownish microlesions in the orohypopharynx be followed up without biopsy or endoscopic resection?

BACKGROUND: Narrow-band imaging (NBI) is useful for detecting superficial oropharyngeal lesions. However, the diagnostic and treatment guidelines for NBI are not established. The aim of the present study was to evaluate the treatment strategy for these microlesions. METHODS: From October 2008 to September 2009, 68 flat-type brownish microlesions were observed in the orohypopharynx using NBI. Lesions were examined via magnifying NBI (M-NBI) and followed up without biopsy or endoscopic resection for >12 months. To clarify the characteristics, lesions were compared with the endoscopic characteristics of flat-type lesions diagnosed by biopsy and endoscopic resection as squamous cell carcinoma and high-grade intraepithelial neoplasia. RESULTS: The average diameter of the 68 lesions was 1.6 mm (range, 0.5-5 mm). At the 1-year follow up, 19 lesions had disappeared. No size increases or morphological changes wereobserved among 49 lesions followed for >1 year. At 2 years, 10 patients had dropped out and 11 lesions had disappeared. No changes were observed among 28 lesions followed for >2 years. Of the flat-type lesions as squamous cell carcinoma and high-grade intraepithelial neoplasia, a distinct border and irregular distribution of atypical vessels were observed in all cases using M-NBI. These findings were observed in two of 68 flat-type brownish microlesions during follow up. CONCLUSION: Although there is some possibility of squamous cell carcinoma or high-grade intraepithelial neoplasia, flat-type microlesions of ≤5 mm diameter in the orohypopharynx may be followed for up to 2 years without biopsy or endoscopic resection.

Use of transoral endoscopy for pharyngeal examination: cross-sectional analysis.

BACKGROUND AND AIM: Transoral endoscopy with narrow band imaging (NBI) is useful for identifying early-stage head and neck cancer. However, the screening capability of transoral upper gastrointestinal endoscopy has not yet been systematically evaluated. We evaluated the usefulness of transoral upper gastrointestinal endoscopy for pharyngeal examination. METHODS: This cross-sectional study evaluated 480 patients. All endoscopic pharyngeal examinations with NBI were carried out in accordance with prescribed procedures, consisting of 10 images each and all images were assessed by a blinded reviewer. We examined the association between the diagnostic usefulness of pharyngeal examination and other factors. RESULTS: Median subject age was 64 years (range 22-90 years), and 64% were male. Almost all patients (98%) had an Eastern Cooperative Oncology Group Performance Status of 0 or 1.Butylscopolamine bromide was given to 382 patients (80%), and a sedative was given to 460 (96%) patients. Median observation time was 74 s (range, 16-362 s), resulting in a mean of 9.0 usable images per patient. However, photographs of the right and left pyriform sinuses were consistently poor. Ordered logistic regression analysis showed that quality images were positively correlated with increased patient age. CONCLUSIONS: Transoral endoscopic examination was possible in most patients for screening of the head and neck. However, results were poor in the pyriform sinuses, indicating that additional improvements of examination methods and instruments are needed to enhance screening accuracy.

Outpatient hybrid endoscopic submucosal dissection with SOUTEN for early gastric cancer, followed by endoscopic suturing of the mucosal defect: A case report.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is becoming more common for early gastric cancer, it requires more advanced techniques and a longer treatment duration than endoscopic mucosal resection. Hybrid ESD using a multifunctional snare (SOUTEN) has been reported to be effective for colorectal lesions, as it can reduce treatment duration. Endoscopic suturing of post-ESD mucosal defects has been reported to reduce the incidence of ESD-related complications. CASE SUMMARY: This study reports outpatient hybrid ESD for early gastric cancer using SOUTEN, followed by endoscopic suturing of post-ESD mucosal defects in an 86-year-old man. On referral for ESD, a 10-mm flat, depressed lesion was found on the posterior wall of the gastric antrum, the depth of which was expected to be mucosal. Given his history of delirium, we performed outpatient endoscopic treatment. The procedure used was hybrid ESD using SOUTEN to reduce the duration of treatment and endoscopic suturing of post-ESD mucosal ESD defects to reduce complications. The procedure time was 62 min and the lesion was completely resected based on histopathological examination, with no reported postoperative complications. CONCLUSION: This safe and useful procedure may be especially important for outpatient endoscopic treatment.

Large-cell Neuroendocrine Carcinoma of the Lung with Carcinoid Syndrome.

A 76-year-old woman was admitted to our hospital for refractory diarrhea with a poor antidiarrheal effect. Chest and abdominal computed tomography revealed a 24×22-mm mass in the left upper lobe of lung and multiple masses in the liver. Urine 5-Hydroxy indol acetic acid was markedly elevated. A liver biopsy revealed large-cell neuroendocrine carcinoma with serotonin production, suggestive of a lung origin, and a lung biopsy revealed combined large-cell neuroendocrine carcinoma and squamous cell carcinoma. Therefore, we made a definitive diagnosis of carcinoid syndrome caused by large-cell neuroendocrine carcinoma of the lung. Although chemotherapy was performed after diagnosis, the patient died 50 days postadmission.

Can magnifying endoscopy with narrow band imaging be useful for low grade adenomas in preoperative biopsy specimens?

BACKGROUND: In biopsy specimens with low grade adenomas, it is often difficult to identify the presence of high grade adenomas or early carcinomas and low grade adenomas preoperatively, and clear guidelines have not yet been defined for the applicability of endoscopic treatment to low grade adenomas identified in biopsy specimens. METHODS: We aimed to clarify the usefulness of magnifying endoscopy with narrow band imaging (NBI) compared to conventional white light endoscopy for diagnosing actual high grade adenomas or early carcinomas with low grade adenomas, using the VS (microvascular pattern [V] and microsurface pattern [S]) classification for low grade adenomas in biopsy specimens. The study cohort consisted of 135 patients who were diagnosed with low grade adenomas in preoperative biopsy specimens and received endoscopic submucosal dissection. RESULTS: In the elevated type of lesion, magnifying endoscopy with NBI diagnosed high grade adenomas or early carcinomas at a higher sensitivity and specificity than conventional white light endoscopy (82.4 vs. 70.6%, P = 0.391, 97.3 vs. 54.7%, P < 0.0001). In the depressed macroscopic type of lesion, magnifying endoscopy with NBI also diagnosed high grade adenomas or early carcinomas at a higher sensitivity (95.5 vs. 68.2%, P = 0.0459) than conventional white light endoscopy. Although the specificity was high, at 100%, the difference when compared to conventional white light endoscopy was not significant (100 vs. 100%, P > 0.99). CONCLUSIONS: For low grade adenomas in biopsy specimens, it is vital to take sufficient consideration of endoscopic findings and not take action based only on the biopsy results. If a decision is made using the VS classification with magnifying endoscopy with NBI, actual high grade adenomas or early carcinomas can be differentiated from low grade adenomas so that endoscopic treatment can be performed more strictly.

[A case of disseminated carcinomatosis of bone marrow treated by S-1 and cisplatin after distal gastrectomy for early gastric cancer].

Patients with bone metastasis originating from gastric cancer experience complications from DIC. They are treated with anticoagulation therapy or platelet transfusion, but their prognosis is poor. Our case was a 50-year-old male who had undergone distal gastrectomy for early gastric cancer[pT1a(M)N0M0, pStage I a]ten years previously. He was admitted to our hospital complaining of backache. As a result of his examination, he was diagnosed with disseminated carcinosis of bone marrow with DIC as a postoperative recurrence of gastric cancer. The patient was treated with combination chemotherapy of S-1 and cisplatin(S-1 80 mg/body, po, day 1-21 and cisplatin 50mg/body, iv, day 8). After one course of treatment, DIC was resolved and his pain was relieved. He survived for about nine months. S-1 and cisplatin are considered to be effective for disseminated carcinosis of bone marrow.

Diagnostic ability of Japan Narrow-Band Imaging Expert Team classification for colorectal lesions by magnifying endoscopy with blue laser imaging versus narrow-band imaging.

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.

Visual assessment of colorectal flat and depressed lesions by using narrow band imaging.

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.

Hypomagnesemia associated with a proton pump inhibitor.

Severe hypomagnesemia is a serious clinical condition. Proton pump inhibitor (PPI) induced hypomagnesemia has been recognized since 2006. In March 2011 the U.S. Food and Drug Administration advised that long-term use of PPI can induce hypomagnesemia. We report the first Japanese case of hypomagnesemia associated with chronic use of PPIs in a 64-year-old man hospitalized for nausea, bilateral ankle arthritis, and tremor of the extremities who had convulsions 3 days after admission. Blood analysis showed severe hypomagnesemia. He had been taking rabeprazole (10 mg/day) for 5 years. After stopping rabeprazole and correcting the electrolytes imbalances, his symptoms improved without recurrence.