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[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

Purpose: Docetaxel, cisplatin, and 5-fluorouracil (DCF) have high response rates, but severe neutropenia is frequently observed. The occurrence of neutropenia is associated with high histological response in solid tumors, and it might be associated with tumor shrinkage after DCF therapy. This study aimed to determine the genetic polymorphisms involved in the clinical response to preoperative DCF therapy in esophageal cancer patients.Methods: We included 56 patients with measurable lesions who received preoperative DCF therapy for esophageal cancer. Twenty-one genetic polymorphisms were analyzed, and univariate logistic regression analysis was used to evaluate the association between genetic polymorphisms and tumor shrinkage. A multivariate logistic regression analysis adjusted for T category and tumor location and a univariate analysis for potential genetic factors with P values < 0.05 were performed to explore the predictive factors and to estimate odds ratios and their 95% confidence intervals.Results: No patient achieved a complete response, whereas 20 patients achieved a partial response, 31 patients had stable disease, and 5 patients had progressive disease. Although no association was found between pharmacokinetic-related gene polymorphisms, XRCC3 rs17997944 was extracted as the only genetic factor that affected tumor shrinkage (P = 0.033) by univariate analysis. The multivariate analysis adjusted for T category and tumor site also showed that XRCC3 rs1799794: AA was a predictive factor that affected tumor shrinkage (odds ratio, 0.243; 95% confidence interval, 0.065–0.914; P = 0.036).Conclusion: XRCC3 rs1799794, which is involved in homologous recombination, is a genetic factor that affects clinical responses to DCF therapy.

Helicobacter pylori (H. pylori) eradication success increases the incidence of erosive esophagitis by normalization of gastric acid secretion. The aim of this study is to clarify predictors and tim...

Background Endocytoscope systems (ECS) can visualize cellular nuclei of the mucosa of the gastrointestinal tract and are predicted to provide real-time microscopic diagnosis. However, their practical diagnostic performance remains unclear. Therefore, we conducted a multicenter prospective study to evaluate the visualization of superficial esophageal neoplasm in vivo using an ECS, and its diagnostic capability. Methods The study target was histologically confirmed squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN). An integrated ECS was used to obtain ECS images. In each patient, three ECS images of cancerous and corresponding noncancerous regions were selected for evaluation. A pathological review board of five certified pathologists made the final diagnosis of the images. The primary endpoint was the sensitivity of ECS diagnosis by pathologists. Results ECS images of 68 patients were assessed: 42 lesions were mucosal SCC, 13 were submucosal SCC, and 13 were HGIN. The rate of assessable images was 96% (95% CI 87.6–99.1). The sensitivity of ECS diagnosis by pathologists was 88% (95% CI 77.2–94.5). Conclusions ECS can provide high-quality images of cancerous lesions and a high diagnostic accuracy by pathologists, and could be useful for real-time endoscopic histological diagnosis of SCC and HGIN. Trial registration The UMIN Clinical Trials Registry Identification Number: 000004218

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

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real‐world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life‐threatening complications occurred in 0.5%, but there were no treatment‐related deaths. During a median follow‐up period of 46.1 months (range 1–113), the 3‐year overall survival rate, relapse‐free survival rate, cause‐specific survival rate, and larynx‐preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276., This is the first report on nationwide survival data and pathological criteria of superficial head and neck cancer. Transoral surgery for superficial head and neck cancer was safe and offered highly curative minimally invasive treatment preserving organs and their function. Subepithelial invasion was clinically useful predictor of recurrence after transoral surgery.

A drawback of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is the development of metachronous gastric cancer (MGC). While MGC after ESD for differentiated-type (D-) EGC was well understood, little is known about MGC occurring after ESD for undifferentiated-type (UD-) EGC, because ESD had not been indicated. We evaluated the incidence and treatment outcomes of MGC after ESD of UD-EGC. This study is a post hoc analysis of JCOG1009/1010, a multicenter trial to evaluate the efficacy and safety of ESD for UD-EGC. The patients who underwent curative ESD of index solitary UD-EGC were analyzed. Surveillance endoscopy was performed biannually for the first 3 years and thereafter annually. We assessed the time to MGC occurrence after ESD, lesion characteristics, and treatment outcomes of MGC. Time to MGC occurrence was estimated by cumulative incidence function, with death and total gastrectomy as competing risks. A total of 198 patients were included in this study. During a median follow-up period of 5.8 years, 4 patients (2%) developed MGC. Median time to MGC occurrence was 4.5 years (range: 3.1–5.4). Five-year cumulative incidence of MGC was 1.0% (95% CI: 0.2–3.3%). Two MGCs were histologically D-EGC, and the remaining two were UD-EGC. The median tumor size of MGCs was 1.0 cm (range: 0.7–1.7), and the depth of invasion (M/SM1/SM2) was 2/1/1, respectively. Three patients achieved curative resection with repeated ESD. MGC does not occur commonly after curative ESD of UD-EGC, and repeated ESD could contribute to stomach preservation.

Background To decrease the risk of bleeding or perforation, ischemic polypectomy is performed using a detachable snare or endoclip with double-balloon endoscopy (DBE) for small-bowel polyps in patients with Peutz – Jeghers syndrome. The aim of this study was to determine the effectiveness and feasibility of ischemic polypectomy. Methods We retrospectively reviewed patients who underwent two or more sessions of ischemic polypectomy using DBE from July 2004 to August 2017. Results 67 therapeutic DBEs were performed in nine patients during the study period and 352 polyps were treated. The median observation period was 34 months (range 12 – 66). There was a declining trend over time in the median number of polyps > 15 mm treated per patient first DBE session 6, second 2, third 1.5, fourth 0.5, fifth 0.5; P = 0.11, Friedman test). No patient required laparotomy due to intussusception during the study period. One patient developed mild acute pancreatitis after the procedure. Conclusions Ischemic polypectomy was feasible for the control of small-bowel polyps in patients with Peutz – Jeghers syndrome.

Background and aims Oxygen saturation (OS) imaging is a novel technique that directly measures and visualizes the tissue oxygen saturation at the surface of the GI tract. Our purpose was to evaluate the ability of OS imaging to visualize the action mode of photodynamic therapy (PDT). Methods Eight patients with local recurrence after chemoradiotherapy for esophageal cancer were enrolled. OS imaging observation was performed before PDT, after 100 J/cm2 illumination and illumination completion, and on the second day. Results OS imaging showed an extreme change in the hypoxic state in the illuminated area, although the change was near invisible on white-light imaging. The median tissue oxygen saturation value at the tumor lesion was 61.5% (range, 36%-91%) before PDT and significantly decreased immediately after illumination: 11% (range, 0%-57%) after 100 J/cm2 illumination, 1% (range, 0%-6%) at PDT completion, and 2% (range, 0%-12%) on the second day. Conclusions OS imaging could be a useful tool to visualize changes after PDT.

The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship between severe neutropenia and genetic polymorphisms in patients treated with preoperative DCF chemotherapy. A total of 158 patients were investigated for their absolute neutrophil count (ANC) within the first cycle of DCF chemotherapy at the National Cancer Center (NCC) Hospital East. DNA samples obtained from the NCC Biobank Registry were used for the analysis of nine genetic polymorphisms related to docetaxel pharmacokinetics. These genotypes were evaluated for their association with severe neutropenia, and further their risk factors were examined using a multivariate logistic regression. A total 81 (51.3%) patients developed severe neutropenia. Multivariate analysis revealed that age (OR 1.054; CI 1.008–1.102, P = 0.022), baseline ANC (OR 1.019; CI 1.002–1.037, P = 0.030), ABCB1 3435C>T (OR 2.191; CI 1.087–4.417, P = 0.028) and ABCC2 *+9383C>G (OR 2.342; CI 1.108–4.948, P = 0.026) were significant risk factors for severe neutropenia development. The results from this study showed that age, ANC, ABCB1 3435C>T, and ABCC2 *+9383 G>C increased the incidence of severe neutropenia with the number of identified risk factors. In addition to age and baseline ANC, ABCB1 3435C>T and ABCC2 *+9383C>G were identified as independent predictors for severe neutropenia in esophageal cancer patients treated with DCF chemotherapy.

Background Second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma adversely affect patients’ outcomes and the quality of life; however, an adequate surveillance schedule remains unclear. Methods We analyzed 330 patients with early esophageal squamous cell carcinoma who underwent endoscopic resection and were registered in the multicenter cohort study to evaluate adequate surveillance for detection of second primary head and neck cancers. Gastrointestinal endoscopists examined the head and neck regions after 3–6 months of endoscopic resection for esophageal squamous cell carcinoma and subsequently every 6 months. An otolaryngologist also examined the head and neck regions at the time of endoscopic resection for esophageal squamous cell carcinoma and at 12 months intervals thereafter. Results During the median follow-up period of 49.4 months (1.3–81.2 months), 33 second primary head and neck cancers were newly detected in 20 patients (6%). The tumor site was as follows: 22 lesions in the hypopharynx, eight lesions in the oropharynx, two lesions in larynx and one lesion in the oral cavity. The 2-year cumulative incidence rate of second primary head and neck cancers was 3.7%. Among them, 17 patients with 29 lesions were treated by transoral surgery. One patient with two synchronous lesions was treated by radiotherapy. Two lesions in two patients were not detected after biopsy. All patients were cured with preserved laryngeal function. Conclusions Surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months could detect second primary head and neck cancers at an early stage, thereby facilitating minimally invasive treatment.

Prediction of the invasive depth is the objective of endoscopic observation for digestive cancer. In superficial esophageal cancer, a close relationship between microvascular patterns observed by magnifying endoscopy with narrow-band imaging (M-NBI) and pathological depth of invasion is well known. The ability of M-NBI to predict the invasion depth in superficial pharyngeal squamous cell carcinoma (SPSCC) has been seldom evaluated. This study aimed to clarify the relationship between the microvasculature patterns and pathological depth in SPSCC. SPSCC lesions evaluated with M-NBI followed by endoscopic resection were analyzed between April 2010 and March 2017. Endoscopic images were classified as microvasculature tumor types B1, B2, and B3 according to the Japan Esophageal Society classification. The pathological depth of invasion was described as either squamous cell carcinoma in situ (Tis) or invasive subepithelial cancer, and the tumor thickness of all lesions was examined. Data were analyzed using the unpaired t, χ2, or Mann–Whitney U test. Type B1 and type B2/B3 (35/3) microvessels were found in 180 lesions (82%) and 39 (18%), respectively. Of the flat lesions, 115 (83%) were classified as Tis and 23 (17%) as subepithelial cancer. Positive and negative predictive values of the B1 vessels were 77% and 82%, respectively. Additional analysis showed that the positive predictive value of the B1 vessels for the flat-type lesions was 87%; the negative predictive value for the elevated lesions was 93%. Microvascular patterns observed by M-NBI are an important factor in predicting the pathological depth of invasion.

Background Many patients with familial adenomatous polyposis (FAP) have adenomatous polyps of the duodenum and the jejunum. We aimed to elucidate the long-term outcomes after double-balloon endoscopy (DBE)-assisted endoscopic resection of duodenal and jejunal polyps in patients with FAP. Methods We retrospectively reviewed patients who underwent more than two sessions of endoscopic resection using DBE from August 2004 to July 2018. Results A total of 72 DBEs were performed in eight patients (median age 30 years, range 12–53; 1.4 DBE procedures/patient-year) during the study period, and 1237 polyps were resected. The median observation period was 77.5 months (range 8–167). There were 11 adverse events, including seven delayed bleeds and four episodes of acute pancreatitis. No delayed bleeding occurred after cold polypectomy. Although, in one patient, one endoscopically resected duodenal polyp was diagnosed as being intramucosal carcinoma, none of the patients developed an advanced duodenal or jejunal cancer during the study period. Conclusions Endoscopic resection of duodenal and jejunal polyposis using DBE in patients with FAP can be performed safely, efficiently, and effectively.

Local recurrence after definitive chemoradiotherapy, if diagnosed early, can be cured by salvage endoscopic therapy, which allows organ preservation and contributes to maintaining patient quality of life. This study aimed to investigate early endoscopic findings of local recurrence in post-definitive chemoradiotherapy patients. Between January 2008 and June 2012, 17 esophageal squamous cell carcinoma patients with no metastasis but local recurrence after definitive chemoradiotherapy were enrolled. We attempted to find endoscopic hallmarks suggestive of local recurrence by comparing pre- and post-local recurrence diagnostic images. The influence of follow-up schedule on chosen salvage therapy type was also investigated. Endoscopic local recurrence findings included eight submucosal tumors, five ulcers, and four erosions. Upon review of prior images, findings suggestive of local recurrence were detected in seven patients, including six submucosal tumors and one erosion, all of which were smaller than 10 mm. These lesions had changed morphologically at local recurrence diagnosis: three submucosal tumors had become larger and three submucosal tumors and one erosion had changed to ulcers. Of 12 patients with cT1 at local recurrence, four (33%) underwent follow-up endoscopy within 1 month of local recurrence findings and 11 patients (92%) were treated with salvage endoscopic therapy. Endoscopists should be aware that SMTs or erosions, even those smaller than 10 mm, can indicate local recurrence after complete response to definitive chemoradiotherapy. Follow-up endoscopy should be performed within 1–2 months if findings suggestive of local recurrence are observed on prior endoscopy, even when biopsy results are negative.

The clinical application of photodynamic therapy (PDT) for gastrointestinal (GI) neoplastic lesions has been developed with appreciation for the great efforts and kind support of Dr. Tom Dougherty and his followers' contributions. There are several published studies on clinical PDT in the field of GI oncology. Esophageal cancer was one of the first clinical indications for PDT that was approved as an endoscopic procedure in both the United States and Japan. PDT was initially used as a palliative local treatment for patients with obstructive esophageal cancer. PDT is also indicated for eradicative therapy for dysplastic Barret's esophagus, which is the precursor state of esophageal adenocarcinoma, with the support of level one evidence. In Japan, PDT was approved as a curative treatment for superficial esophageal carcinoma lesions, which are difficult to treat with endoscopic resection. Further, PDT using second-generation photosensitizers is approved for early local failure after radiotherapy, for which treatment with other modalities is difficult. PDT has also been assessed in other GI cancers, including gastric cancer, biliary cancer and pancreatic cancer. In this review, we overview the history and state of PDT for GI cancer.

Immune checkpoint inhibitors may enhance the efficacy of radiotherapy (RT) in cancer treatment but the effect remains unknown in metastatic gastric cancer (mGC). This study aimed to compare the tumor shrinkage by palliative RT for mGC patients with or without previous exposure to anti-PD-1 therapy. Data of 36 mGC patients who had received palliative RT from April 2013 to May 2019 were analyzed. Primary tumor responses were evaluated through a volumetric measurement-based method using computed tomography (CT) and endoscopic responses were evaluated in patients who underwent endoscopy before and after RT. Tumor microenvironment (TME) immune status was investigated by analyzing tumor-infiltrating lymphocytes by flow cytometry. Among 36 patients, 18 had previous exposure to anti-PD-1 before RT showing no significant differences in baseline characteristics with the other 18 patients without exposure to anti-PD-1 treatment. Tumor responses were observed in 28% (5/18) and none (0/18) in the anti-PD-1-exposed vs. naive group, respectively (P = 0.045). Five out of eight patients in the anti-PD-1-exposed group, who underwent endoscopy after RT showed partial response, but none in the anti-PD-1-naive patients showed response (P = 0.026). Increase in the CD8+ T cell/effector regulatory T cell ratio in TILs after anti-PD-1 therapy was noted in three responders to RT, but not in the other three non-responders. Prior exposure to anti-PD-1 therapy increases tumor response to RT. Immune profiling suggests that anti-PD-1 therapy may enhance the efficacy of RT by immunoactivation in the TME.

The width of mucosal defects after endoscopic submucosal dissection (ESD) of esophageal squamous cell carcinoma (ESCC) is known to be a risk factor for esophageal strictures. Although steroid injection and oral steroid have recently been reported as prophylactic treatments, these were shown to be ineffective in a subset of patients with post-ESD mucosal defects involving the entire circumference of the esophagus. The aim of this study was to demonstrate outcome with prophylactic steroid administration for post-ESD mucosal defects involving the entire circumference, and to explore risk factors for esophageal strictures except for circumference of the esophagus. Between November 2012 and August 2018, we enrolled patients with post-ESD mucosal defects involving the entire circumference of the esophagus who had received steroid injection (triamcinolone acetonide 50–100 mg, given immediately after ESD) followed by oral steroid (prednisolone 30 mg/day, tapered gradually over 8 weeks) as prophylactic treatment. Esophageal stricture was defined as case where ordinary-sized endoscope could not pass through post-ESD site, thus requiring endoscopic balloon dilation (EBD) repeatedly until relief of stricture was achieved. We retrospectively evaluated the rates of strictures, refractory strictures (requiring ≥ 6 EBD procedures) and unimproved strictures (not improvable by repeated EBD alone) and explored risk factors for strictures. A total of 26 patients met the including criteria. The rates of strictures, refractory strictures, and unimproved strictures were 62%, 38%, and 12%, respectively. The pre-ESD longitudinal extension of the lesion > 5 cm was identified as a risk factor for refractory strictures, suggesting that lesions with this factor had a shorter time to stricture development, required more EBD procedures, and longer EBD durations. Although additional study is required in a larger number of patients, careful consideration needs to be given to ESD as an indication for large spreading ESCC involving the entire circumference of esophagus given its high stricture risk.

BACKGROUND Artificial intelligence (AI) has made considerable progress in image recognition, especially in the analysis of endoscopic images. The availability of large-scale annotated datasets has contributed to the recent progress in this field. Datasets of high-quality annotated endoscopic images are widely available, particularly in Japan. A system for collecting annotated data reported daily could aid in accumulating a significant number of high-quality annotated datasets. AIM We assessed the validity of using daily annotated endoscopic images in a constructed reporting system for a prototype AI model for polyp detection. METHODS We constructed an automated collection system for daily annotated datasets from an endoscopy reporting system. The key images were selected and annotated for each case only during daily practice, not to be performed retrospectively. We automatically extracted annotated endoscopic images of diminutive colon polyps that had been diagnosed (study period March-September 2018) using the keywords of diagnostic information, and additionally collect the normal colon images. The collected dataset was devised into training and validation to build and evaluate the AI system. The detection model was developed using a deep learning algorithm, RetinaNet. RESULTS The automated system collected endoscopic images (47,391) from colonoscopies (745), and extracted key colon polyp images (1356) with localized annotations. The sensitivity, specificity, and accuracy of our AI model were 97.0%, 97.7%, and 97.3% (n = 300), respectively. CONCLUSION The automated system enabled the development of a high-performance colon polyp detector using images in endoscopy reporting system without the efforts of retrospective annotation works.

Key Points Question Is the performance of endoscopic ultrasonography after conventional endoscopy associated with improvements in diagnosing the invasion depth of esophageal squamous cell carcinoma? Findings In this diagnostic study of 372 patients with esophageal cancer, the performance of endoscopic ultrasonography after nonmagnifying and magnifying endoscopy was not associated with improvements in diagnostic performance for differentiating between submucosal and mucosal cancers in terms of overdiagnosis and accuracy. Meaning This study suggests that endoscopic ultrasonography after nonmagnifying and magnifying endoscopy is not helpful for evaluating the invasion depth of T1 esophageal squamous cell carcinoma., Importance Distinguishing between mucosal and submucosal cancers is important for selecting the optimal treatment for patients with esophageal squamous cell carcinoma (ESCC); however, standard procedures for diagnosing cancer invasion depth have not yet been determined. Objective To evaluate the diagnostic performance of endoscopic ultrasonography (EUS) after conventional endoscopy for the evaluation of ESCC invasion depth. Design, Setting, and Participants This prospective single-arm confirmatory diagnostic study comprising 372 patients with T1 esophageal cancer was conducted at 41 secondary or tertiary hospitals in Japan. Enrollment began on July 20, 2017; patients were enrolled in 2 steps, with the first registration occurring from August 4, 2017, to December 11, 2019, and the second from August 9, 2017, to December 11, 2019. After the completion of all first and second registration examinations, patients received treatment and were followed up for 30 days, with follow-up ending on February 14, 2020. Patients were eligible for inclusion if they had pathologically or endoscopically diagnosed esophageal cancer with T1 clinical depth of invasion. Interventions In the first registration, nonmagnifying endoscopy (non-ME) and magnifying endoscopy (ME) were used to diagnose cancer invasion depth. In the second registration, patients from the first registration who had cancers invading the muscularis mucosa or submucosa were enrolled and received EUS. After completion of the protocol examinations, patients received treatment with endoscopic resection or esophagectomy. The pathological results of the resected specimens were used as the reference standard for evaluating cancer invasion depth. Main Outcomes and Measures The primary end point was the proportion of overdiagnosis of submucosal cancer (defined as invasion depth >200 μm) after receipt of non-ME and ME, with or without the addition of EUS. The secondary end points were underdiagnosis, sensitivity, and specificity. Results Among 372 patients enrolled in the first registration, 371 received non-ME and ME. Of those, 300 patients were enrolled in the second registration, and 293 patients received EUS. A total of 269 patients (217 men [80.7%]; median age, 69 years; interquartile range, 62-75 years) were included in the final analysis. The addition of EUS was associated with a 6.6% increase in the proportion of overdiagnosis (from 16 of 74 patients [21.6%; 95% CI, 12.9%-32.7%] after non-ME and ME to 29 of 103 patients [28.2%; 95% CI, 19.7%-37.9%] after the addition of EUS; 1-sided P = .93). All subgroup analyses found similar increases in overdiagnosis of submucosal cancer. The addition of EUS was associated with a 4.5% reduction in the proportion of underdiagnosis (from 57 of 195 patients [29.2%; 95% CI, 23.0%-36.2%] after non-ME and ME to 41 of 166 patients [24.7%; 95% CI, 18.3%-32.0%] after the addition of EUS). After non-ME and ME, diagnostic sensitivity was 50.4% (95% CI, 41.0%-59.9%), specificity was 89.6% (95% CI, 83.7%-93.9%), and accuracy was 72.9% (95% CI, 67.1%-78.1%). After the addition of EUS, diagnostic sensitivity was 64.3% (95% CI, 54.9%-73.1%), specificity was 81.2% (95% CI, 74.1%-87.0%), and accuracy was 74.0% (95% CI, 68.3%-79.1%). Conclusions and Relevance This study found that the addition of EUS was not associated with improvements in the diagnostic accuracy of cancer invasion depth. These findings do not support the routine use of EUS after conventional endoscopy for evaluating the invasion depth among patients with T1 ESCC., This study assesses the performance of endoscopic ultrasonography after nonmagnifying and magnifying endoscopy for the diagnosis of cancer invasion depth among patients with esophageal squamous cell carcinoma.

Adenocarcinoma in a Meckel’s diverticulum is rare and difficult to diagnose preoperatively. We report the first case of a metachronous Krukenberg tumor from adenocarcinoma in a Meckel’s diverticulum. A 45-year-old woman was admitted for recurrent abdominal pain. Computed tomography scan showed a lesion with contrast enhancement, and a Meckel’s diverticulum-associated tumor was suspected. Double-ballon enteroscopy revealed intestinal stenosis and biopsy showed adenocarcinoma. Operative findings showed a Meckel’s diverticulum with tumor. Histopathological evaluation revealed well-differentiated adenocarcinoma, interrupted by ectopic gastric mucosa, diagnosed as adenocarcinoma in a Meckel’s diverticulum. Two years postoperatively, a multi-cystic mass with contrast enhancement was observed in the pelvis on imaging evaluation and oophorectomy performed. Histological examination of the resected ovary showed proliferation of atypical glandular ducts, consistent with metastatic adenocarcinoma. This case demonstrates that adenocarcinoma in a Meckel’s diverticulum may result in distant metastases and requires appropriate follow-up.

BACKGROUND AND AIM It is unclear whether second-generation narrow-band imaging (NBI) improves colorectal adenoma detection in clinical practice. We aimed to evaluate the ability of NBI to detect adenomas in academic and community hospitals. METHODS This observational, multicenter study was conducted in four academic and four community hospitals between July 2018 and April 2019. We enrolled patients aged ≥ 20 years who underwent colonoscopy for screening, polyp surveillance, or diagnostic workup. The primary endpoint was the adenoma detection rate (ADR) between NBI (NBI group) and white-light imaging colonoscopies (WLI group) after propensity score (PS) matching. RESULTS Of 1831 patients analyzed before PS matching, the NBI and WLI groups included 742 and 1089 patients, respectively. After PS matching, 711 pairs from both groups were analyzed. ADR and the mean number of adenomas per patient did not differ significantly between the NBI and WLI groups (43.5% vs 44.4%, P = 0.71; 0.90 ± 1.38 vs 0.91 ± 1.40, P = 0.95, respectively). Academic hospitals showed higher ADR in the NBI group (60.5% vs 53.8%), whereas community hospitals showed higher ADR in the WLI group (35.8% vs 40.5%). In the NBI group, ADR was significantly higher among NBI-screening-experienced endoscopists than among NBI-screening-inexperienced endoscopists (63.2% vs 39.2%, P

There are few reports on the technical difficulty of gastric endoscopic submucosal dissection (ESD). The aim of this study was to investigate the factors associated with the technical difficulty of ESD for early gastric cancer (EGC) using the data from the multicenter non-randomized confirmatory trial of expanded indication criteria of ESD (JCOG0607).The major inclusion criteria were as follows: (1) histologically proven intestinal-type adenocarcinoma; (2) cT1aN0M0; (3) lesion without finding of ulcer (UL-negative) with 2 cm in size, or UL-positive with ≤ 3 cm; (4) age 20-75 years. The difficult case was defined as ESD taking ≥ 120 min, piecemeal resection, and/or developing perforation during procedure.Between June 2007 and October 2010, 470 patients were enrolled from 29 institutions. Median procedure time was 79 (range 14-462) min, and it was ≥ 120 min in 127 patients. Twelve patients developed perforation during ESD, and the procedure time was ≥ 120 min in 9 of them. Therefore, 130 patients (27.7%) were identified as difficult cases. Multivariable analysis showed that UL-negative with 5 cm (vs. UL-negative with ≤ 3 cm, odds ratio, 24.993; 95% CI 6.130-101.897, p 0.0001) had the largest odds ratio and followed by UL-negative with 3-5 cm upper or middle portion of stomach and age ≤ 60 years were significantly associated with difficulty.UL-negative lesion with 3 cm, upper or middle portion of stomach and age ≤ 60 years were independent factors associated with technical difficulty of ESD for EGC. Trial registered number was UMIN000000737.

Macrocytosis is associated with an increased risk of squamous cell carcinoma (SCC) arising in the esophagus in men. The aim of this study was to evaluate the association between macrocytosis and metachronous SCC of the esophagus after endoscopic resection (ER) of early esophageal SCC in men. The study group comprised 278 men with early esophageal SCC after ER. The main study variables were as follows: (1) cumulative incidence and total number of metachronous SCC of the esophagus according to the presence or absence of macrocytosis (mean corpuscular volume ≥ 106 fl) and (2) predictors of metachronous SCC of the esophagus as assessed with a multivariate Cox proportional-hazards model. The median follow-up was 50.3 months. Macrocytosis was associated with a higher 2-year cumulative incidence of metachronous SCC of the esophagus (without macrocytosis vs. with macrocytosis: 11.4% vs. 38.1%, p = 0.002). Macrocytosis was also associated with a higher total number of metachronous SCC of the esophagus per 100 person-years (without macrocytosis vs. with macrocytosis: 7.7 vs. 31.5 per 100 person-years, p

Duodenocolic fistula (DCF) is a rare disorder defined by the presence of an internal fistula between the duodenum and colon. Colon cancer, Crohn's disease, diverticulum and duodenal ulcer are common causes of DCF, and vomiting and diarrhea are its main symptoms. We report a 14-year-old boy with DCF who had been treated for a functional gastrointestinal disorder (FGID). The boy had often experienced episodes of vomiting and diarrhea since infancy, and had been diagnosed with FGID. He was referred to our hospital because of a 2-month exacerbation of persistent vomiting and diarrhea. Upper gastrointestinal contrast revealed no abnormalities. Eventually, esophagogastroduodenoscopy detected a duodenal fistula, and DCF was diagnosed by endoscopic fistulography. Colonoscopy showed a diverticulum in the ascending colon near the fistula. In addition, a C13 urea breath test for Helicobacter pylori infection was positive. One hypothetical pathogenesis of his DCF was perforated colonic diverticulitis. Adhesion between the fistula wall and colonic diverticulum near the fistula strongly suggested a relationship between the fistula and the diverticulum. However, he never presented with symptoms of colonic diverticulitis. Thus, a congenital origin was also suspected. After confirming temporary relief from the symptoms by endoscopic closure, surgical closure was performed.

Background and study aims This study was designed to clarify clinicopathological, endoscopic, and genetic characteristics of inverted sessile serrated adenomas/polyps. Patients and methods In this retrospective study, we reviewed the pathology reports of patients treated in our hospital between January 2010 and June 2015 and identified sessile serrated adenomas/polyps that were diagnosed with endoscopic resected specimens. Clinicopathological, endoscopic, and genetic features were compared between the inverted and ordinary types. Results Among the 104 sessile serrated adenomas/polyps, 37 lesions were inverted (35.6 %). The inverted types had two patterns of invasion: expansive and infiltrating growth. Expansive growth was observed in 15 cases (40.5 %) and infiltrating in 22 (59.5 %). Regarding the clinicopathological findings and endoscopic characteristics of the inverted types, presence of adherent mucous, location in the right-side colon, an expanded type-II pit pattern, irregularly dilated vessels, and a depression were demonstrated in 89 % (33/37), 73 % (27/37), 54 % (20/37), 75 % (28/37), and 35 % (13/37), respectively. Contrastingly, these were demonstrated in 86 % (58/67), 84 % (56/67), 55 % (37/67), 58 % (39/67), and 0 % (0/67), respectively, in the ordinary type. In the univariate analysis, male sex and a depression in the adenoma/polyp were significantly associated with inverted types (P Conclusion More than 30 % of sessile serrated adenomas/polyps were pathologically diagnosed as inverted, and approximately 40 % of them were of the expansive growth type and easily diagnosed with endoscopy.

A 67-year-old woman presented with symptoms of bowel obstruction. Radiographic and ultrasonographic findings suggested colo-colonic intussusception caused by a colonic lipoma. Colonoscopy with an endoscope tip balloon was performed for reduction. The intussusception was partially reduced by injecting dilute contrast media with a wedged inflated balloon at the endoscope tip. For definitive treatment of the polyp, ischemia was induced using a detachable snare. The abdominal pain well improved after endoscopic treatment. However, ultrasonography suggested a residual lesion. Another detachable snare was applied to the stalk on day 6. A large amount of dark-red necrotic tissue was passed per anus the following day. One month later, complete scarring of the site was confirmed colonoscopically. This is the first report of curative endoscopic treatment of an intussusception due to a giant colonic lipoma with detachable snares after the reduction with a wedged balloon of colonoscope tip.

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.

Endoscopic ultrasonography (EUS) is reportedly the reliable modality to predict the depth of esophageal squamous cell carcinoma (ESCC), however, most previous studies are retrospective or single-centered. We aimed to evaluate the diagnostic ability of conventional endoscopy and EUS using the data from a multicenter prospective study of endoscopic resection (ER) followed by chemoradiotherapy for cSM1-2N0M0 ESCC (JCOG0508). All lesions were evaluated as cSM cancer with both conventional endoscopy and EUS before enrollment and judged as cSM1 or cSM2 in real time. We compared the clinical and pathological diagnoses for tumor depth and assessed the positive predictive value (PPV) for pSM (pSM/cSM) as the primary endpoint. We also investigated the clinical factors affecting the pathological depth of SM. 175 lesions were examined, and clinical diagnosis was SM1 in 114 and SM2 in 61 lesions. The pathological diagnoses of the epithelium, lamina propria mucosa, muscularis mucosae, SM1, and SM2 were 3, 31, 55, 17, and 69. The PPV for pSM was 49.1% (86/175) in all lesions, 34.2% (39/114) in cSM1 lesions, and 77.0% (47/61) in cSM2 lesions. Multivariable analysis demonstrated that cSM2 (vs. cSM1, OR 6.79) was an independent clinical factor associated with pSM. While the accurate depth diagnosis in cSM ESCC was difficult to make, the clinical diagnosis of SM2 with both conventional endoscopy and EUS was significantly associated with pSM. Furthermore, diagnostic ER could be recommended to confirm the pathological diagnosis especially in cSM1 lesions with both conventional endoscopy and EUS.

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 This study aimed to compare the markers of potential pancreatic injury during antegrade double-balloon endoscopy (DBE) using the newly developed ultrathin EN-580XP system and the conventional EN-580T system. Methods Patients who were scheduled for antegrade DBE during daily clinical practice were enrolled. Clinical background, adverse events, and laboratory data of patients were compared between those who underwent endoscopy using the EN-580XP system and those in whom the EN-580T system was used. The primary end points were pancreatic hyperamylasemia and hyperlipasemia after DBE. Results A total of 295 cases were registered. Pancreatic hyperamylasemia occurred in 2 of 92 patients (2.2 %) in the EN-580XP group and in 28 of 147 patients (19.1 %) in the EN-580 T diagnosis group (P Conclusions The EN-580XP system seemed less harmful to the pancreas during antegrade DBE.

While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC. The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC. Three hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1–99.8). ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.

Little is known about the incidence of metachronous advanced neoplasia (AN) following resection of submucosal invasive colorectal cancer (SM-CRC). Here, we aimed to assess the occurrence of metachronous AN following SM-CRC resection. We retrospectively reviewed consecutive patients who underwent SM-CRC resection at an academic medical center between 2005 and 2013. Among 343 patients, 250 (72.9%) underwent surgical resection or endoscopic resection followed by surgical resection and 93 (27.1%) underwent only endoscopic resection. During a median follow-up period of 61.5 months, the overall incidence of metachronous AN was 7.6%, and the cumulative incidence at 5 years was 6.1%. The cumulative incidence was significantly higher in the endoscopic resection group than in surgical resection group, in patients with colonic disease than in those with rectal disease, and in patients with synchronous AN than in those without. Multivariate analysis revealed that synchronous AN was the only significant risk factor for metachronous AN (HR 4.35; 95% CI 1.88–10.1). These findings imply that depending on synchronous AN, a surveillance protocol following SM-CRC resection can be changed for better detection of metachronous AN.

Objectives Oxygen saturation (OS) imaging is a new method of endoscopic imaging that has clinical applications in oncology which can directly measure tissue oxygen saturation (Sto2) of the surface of gastrointestinal tract without any additional drugs or devices. This imaging technology is expected to contribute to research into cancer biology which leads to clinical benefit such as prediction to efficacy of chemotherapy or radiotherapy. However, adherent substances on tumors such as blood and white coating, pose a challenge for accurate measurements of the StO2 values in tumors. The aim of this study was to develop algorithms for discriminating between the tumors and their adherent substances, and to investigate whether it is possible to evaluate the tumor specific StO2 values excluding adherent substances during OS imaging. Methods We plotted areas of tumors and their adherent substances using white-light images of 50 upper digestive tumors: blood (68 plots); reddish tumor (83 plots); white coating (89 plots); and whitish tumor (79 plots). Scatter diagrams and discriminating algorithms using spectrum signal intensity values were constructed and verified using validation datasets. StO2 values were compared between the tumors and tumor adherent substances using OS images of gastrointestinal tumors. Results The discriminating algorithms and their accuracy rates (AR) were as follows: blood vs. reddish tumor: Y> - 4.90X+7.13 (AR: 95.9%) and white coating vs. whitish tumor: Y< -0.52X+0.17 (AR: 96.0%). The StO2 values (median, [range]) were as follows: blood, 79.3% [37.8%–100.0%]; reddish tumor, 74.5% [62.0%–86.9%]; white coating, 73.8% [42.1%–100.0%]; and whitish tumor, 65.7% [53.0%–76.3%]. Conclusions OS imaging is strongly influenced by adherent substances for evaluating the specific StO2 value of tumors; therefore, it is important to eliminate the information of adherent substances for clinical application of OS imaging.

JCOG0909 is a phase II trial of definitive chemoradiotherapy including salvage treatment for cStage II–III thoracic esophageal cancer; the radiation field for elective regional lymph node irradiation, which can affect patient outcome and adverse event, varied based on the primary tumor site, i.e., upper (Ut), middle (Mt), and lower thoracic (Lt) esophagus. The impact of different primary sites on the safety and efficacy of definitive chemoradiotherapy in JCOG0909 is not well characterized. Patients were categorized into three groups (Ut, Mt, and Lt) according to the primary tumor location. We compared acute adverse events during definitive chemoradiotherapy, complete response (CR) rate, 3-year progression-free survival (PFS), and overall survival (OS) among the 3 groups. Out of the 96 patients enrolled in JCOG0909 between April 2010 and August 2014, 94 patients (16, 59, and 19 patients in the Ut, Mt, and Lt groups, respectively) were included in this exploratory analysis. The proportion of patients with cStage III was 25% in the Ut, 37% in the Mt, and 47% in the Lt group. Grade 3–4 leukopenia, neutropenia, and thrombocytopenia were more frequently observed in the Mt (66%, 54%, and 15%) and Lt groups (84%, 68%, and 16%) than in the Ut group (38%, 44%, and 0%). There was no significant between-group difference with respect to 3-year OS (73.3%, 77.9%, and 57.9%), 3-year PFS (60.0%, 59.3%, and 47.4%), or CR rate (62.5%, 62.7%, and 42.1%). In JCOG0909, the incidence of severe hematological toxicity had a trend toward higher in the Mt and Lt than the Ut esophageal cancer; however, no remarkable difference by primary sites was observed with respect to efficacy endpoints.

Background and Aims Salvage endoscopic submucosal dissection (ESD) after chemoradiotherapy can be technically difficult as a result of radiation-induced fibrosis. We aimed to evaluate the technical feasibility of ESD for local failure after chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) and for other primary lesions within the irradiation field. Methods Consecutive patients treated with ESD for superficial ESCC between December 2009 and May 2017 were investigated retrospectively and stratified into group A (33 patients, 35 lesions; local failure at the primary site after chemoradiotherapy), group B (25 patients, 34 lesions; second primary lesions within the irradiation field), and group C (550 patients, 596 lesions; radiotherapy-naive superficial ESCC). We evaluated procedural success rate, en bloc resection rate, 1-year local relapse-free survival (LRFS) rate, procedure time, and incidence of major adverse events. Results The rates of procedural success and en bloc resection, respectively, were significantly lower in group A (89%, 86%) than in groups B (100%, 100%) and C (100%, 98%). The 1-year LRFS rates were 86%, 100%, and 99% in groups A, B, and C, respectively, and significantly lower in group A than in group C. Serious adverse events including perforation were not observed in groups A and B; perforation occurred only in group C (2.8%). Conclusions ESD is technically feasible in patients with local failure, especially as initial salvage treatment and as treatment for second primary lesions within the irradiation field.

Objectives A Japanese multicenter prospective cohort study examining endoscopic resection (ER) for early gastric cancer (EGC) has been conducted using a Web registry developed to determine the short-term and long-term outcomes based on absolute and expanded indications. We hereby present the short-term outcomes of this study. Methods All consecutive patients with EGC or suspected EGC undergoing ER at 41 participating institutions between July 2010 and June 2012 were enrolled and prospectively registered into the Web registry. The baseline characteristics were entered before ER, and the short-term outcomes were collected at 6 months following ER. Results Nine thousand six hundred and sixteen patients with 10 821 lesions underwent ER (endoscopic submucosal dissection [ESD]: 99.4%). The median procedure time was 76 min, and R0 resections were achieved for 91.6% of the lesions. Postoperative bleeding and intraoperative perforation occurred in 4.4% and 2.3% of the patients, respectively. Significant independent factors correlated with a longer procedure time (120 min or longer) were as follows: tumor size >20 mm, upper-third location, middle-third location, local recurrent lesion, ulcer findings, gastric tube, male gender, and submucosa. Histopathologically, 10 031 lesions were identified as common-type gastric cancers. The median tumor size was 15 mm. Noncurative resections were diagnosed for 18.3% of the lesions. Additional surgery was performed for 48.6% (824 lesions) of the 1695 noncurative ER lesions with a possible risk of lymph node (LN) metastasis. Among them, 64 (7.8%) exhibited LN metastasis. Conclusions This multicenter prospective study showed favorable short-term outcomes for gastric ESD.

Receptor tyrosine kinases (RTKs) play critical roles in gastric cancer (GC) progression and are potential targets for novel molecular-targeted agents or photo-immunotherapies. During patient selection, targeted biopsy is the first step. However, heterogeneous expression of RTKs based on the macroscopic appearance in GC has not been extensively addressed. Accordingly, in this study, we evaluated differences in RTK expression associated with macroscopic appearance in GC. In total, 375 consecutive patients who had undergone gastrectomy at the National Cancer Center Hospital East and who had histologically proven adenocarcinoma, available archived tumor sample, and no history of chemotherapy were enrolled in this study. For these cases, tissue microarray (TMA) samples were examined using immunohistochemistry (IHC). Based on the results of IHC, cases were selected for detailed examination. We re-evaluated IHC scores in more than three tumor blocks per case and comparatively evaluated differences in IHC expression in RTKs between the mucosal portion (MuP) and invasive portion (InP). Human epidermal growth factor receptor 2 (HER2)-, epidermal growth factor receptor (EGFR)-, and mesenchymal epithelial transition factor (c-MET)-positive rates were 6, 9, and 20%, respectively. Twenty-two cases were then analyzed to assess differences in IHC expression levels in the same lesion. Concordance rates of positive staining of HER2, EGFR, and MET between MuP and whole tumor were 100, 40, and 56% and those with InP were 46, 100, and 56%. To avoid underestimating expression status, biopsies must be taken from MuP for HER2, InP for EGFR, and both proportions for c-MET.

Tumor regression grade of the primary tumor (TRG-PT) and residual lymph node metastasis have been pathologically determined in esophageal squamous cell carcinoma (ESCC) patients who had received neoadjuvant chemotherapy (nCT) followed by surgery; however, TRG of the metastatic tumor involving lymph nodes (LN) has not yet been determined. The aim of the present study was to clarify the impact of TRG on the prognosis of ESCC patients. ESCC patients (n = 110) who had received nCT followed by surgery were enrolled. Dissected LN were classified into 2 categories: plausible positive metastatic LN (pp-MLN) where viable and/or degenerated ESCC cells and/or tissue modifications were observed, and non-metastatic LN (non-MLN) where neither of them was observed. We defined nCT-effective rate (CER) as the ratio of the number of pp-MLN that showed tumor regression to the total number of pp-MLN, and divided CER into low-CER (LCER; ≥0% and

The aim of this pilot study is to investigate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) in the evaluation of depth of invasion in colorectal lesions. Patients with colorectal lesions eligible for either endoscopic treatment or surgery were enrolled in the study. Tumor’s depth of invasion was classified as mucosal or slight submucosal (M-SM1) and deep submucosal invasion or deeper (SM2 or deeper). White light endoscopy (WLE), magnifying narrow band imaging (M-NBI), and magnifying chromoendoscopy (M-CE) were used to assess colorectal lesions, and pCLE was used to identify tumor’s features related to SM2 or deeper. The diagnostic classification of depth of invasion was obtained by correlating pCLE findings with histology results (on-site diagnosis). All colorectal lesions were stratified by a second endoscopist who was blinded to any clinical and histological information with the use of WLE, M-NBI, M-CE, and pCLE (off-line review). A total of 22 colorectal lesions were analyzed: seven were adenoma, ten intramucosal cancer, and five SM2 or deeper cancer. With respect to pCLE findings, loss of crypt structure was seen in all SM2 or deeper cancers and only in one M-SM1 lesion. Sensitivity, specificity, and accuracy of WLE, M-NBI, and M-CE in off-line review were 60/94/86, 60/94/86, and 80/94/91%, respectively. Sensitivity/specificity/accuracy of pCLE in off-line review were 80/94/91%, respectively. The inter-observer agreement of pCLE between on-site diagnosis and off-line review was 0.64 (95%CI 0.27–1.0). pCLE may represent a useful tool to evaluate the depth of invasion in colorectal lesions.

Human epidermal growth factor receptor 2 (HER2) expression in gastric cancer is highly heterogeneous. Therefore, it is important to take endoscopic samples from appropriate tumor sites. Between January 2008 and April 2015, patients with gastric or gastroesophageal junction cancer with histologically confirmed adenocarcinoma were included. Surgical samples or endoscopic biopsy samples were examined for HER2 using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Tissues were considered to be HER2 positive when either assessment revealed either an IHC score of 3+ or an IHC score of 2+ accompanied by a positive FISH result. Endoscopic findings were retrieved in all cases where available, and we examined the portion from which a biopsy was obtained. Out of the 612 patients included in the study, 104 (17%) were HER2 positive. The proportion of HER2-positive gastric tumors with differentiated (vs. undifferentiated) histology was significantly higher (29 vs. 6%, respectively; p

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.

Photodynamic therapy (PDT) using a conventional photosensitizer was approved for esophageal cancer in the early 1990s; however, it was replaced by other conventional treatment modalities in clinical practice because of the high frequency of cutaneous phototoxicity and esophageal stricture after the procedure. The second-generation photosensitizer, talaporfin sodium, which features more rapid clearance from the body, was developed to reduce skin phototoxicity, and talaporfin sodium can be excited at longer-wavelength lights comparing with a conventional photosensitizer. Endoscopic PDT using talaporfin sodium was initially developed for the curative treatment of central-type early lung cancer in Japan, and was approved in the early 2000s. After preclinical experiments, PDT using talaporfin sodium was investigated for patients with local failure after chemoradiotherapy, which was the most serious unmet need in the practice of esophageal cancer. According to the favorable results of a multi-institutional clinical trial, PDT using talaporfin sodium was approved as an endoscopic salvage treatment for patients with local failure after chemoradiotherapy for esophageal cancer. While PDT using talaporfin sodium is gradually spreading in clinical practice, further evaluation at the point of clinical benefit is necessary to determine the importance of PDT in the treatment of esophageal cancer.

An 18-year-old man presented after undergoing multiple investigations for abdominal pain. Retrograde double-balloon enteroscopy showed a protruding red lesion in the ileum with small ulcers, approximately 75 cm proximal to the ileocecal valve, resulting in an intussusception. An inverted Meckel’s diverticulum was strongly suspected. Pressure was applied to the protruding lesion using contrast medium injection after wedging the lumen with a balloon. The intussusception partially reduced, avoiding the need for emergent surgery. Endoscopic tattooing was performed to mark the lesion for subsequent resection. Elective laparoscopy-assisted surgery with minimum laparotomy revealed an inverted Meckel’s diverticulum, which was resected.

A "skirt" is a slightly elevated flat lesion with wide pits occasionally observed at the margin of laterally spreading tumors (LSTs). However, the endoscopic treatment outcomes of LSTs with skirts have not been clarified. The aim of this study was to evaluate the endoscopic treatment outcomes of LSTs with skirts.Between February 2006 and March 2014, 996 LSTs were retrospectively examined to assess the clinicopathologic characteristics, procedure time, en bloc resection rate, R0 resection rate, adverse events, and local recurrence rate of endoscopic submucosal dissection (ESD) and of endoscopic resection.Endoscopic treatment was performed in 35 cases of LSTs with skirts (ratio of ESD to endoscopic piecemeal mucosal resection [EPMR], 32:3) and 961 cases of LSTs without skirts (ratio of ESD to EMR to EPMR to polypectomy, 381:275:114:191). LSTs with a skirt were associated with a significantly higher recurrence rate (P .01). In both ESD and EPMR, LSTs with a skirt were associated with a higher recurrence rate when compared with LSTs without a skirt (odds ratio, 12.7; P = .032, and odds ratio, 12.3; P = .061, respectively). Multivariate analysis demonstrated that the presence of the skirt and piecemeal resection were significant predictors of local recurrence.LSTs with skirts had a significantly higher local recurrence rate after endoscopic treatment compared with LSTs without skirts, especially after EPMR. Therefore, ESD should be recommended as an endoscopic treatment for LSTs with skirts to minimize local recurrence.