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Background The Cryoballoon focal ablation system (CbFAS) for dysplastic Barrett’s esophagus is simple, time-saving and has high therapeutic efficacy. This study aimed to evaluate the technical feasibility and tissue damage with combination therapy of endoscopic resection (ER) and CbFAS in porcine models. Methods Three pigs (A, B, and C) were included, and all ER procedures were performed by endoscopic mucosal resection using the Cap method (EMR). Combination therapy for each pig was performed as follows: (a) CbFAS was performed for a post-EMR mucosal defect for Pig A; (b) CbFAS for post-EMR scar for Pig B, and (c) EMR for post-CbFAS scar for Pig C. All pigs were euthanized at 32 days after the initial procedure, and the tissue damage was evaluated. Results All endoscopic procedures were followed as scheduled. None of the subjects experienced anorexia, rapid weight loss, bleeding, and perforation during the observation period. They were euthanized at 32 days after the initial endoscopic procedure. On histological assessment, there was little difference between the tissue that was treated with CbFAS alone and that treated with CbFAS in combination with ER. Conclusion Combination therapy with ER and CbFAS can be technically feasible, and its outcome was not significantly different from CbFAS alone in terms of tissue damage.

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.

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.

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.

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.

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.

JCOG9801, a randomized phase III trial, reported that vincristine, cyclophosphamide, doxorubicin and prednisone (VCAP); doxorubicin, ranimustine and prednisone (AMP); and vindesine, etoposide, carboplatin and prednisone (VECP) (VCAP-AMP-VECP; mLSG15) showed superior clinical outcomes when compared to cyclophosphamide, doxorubicin, vincristine and prednisone every 2 weeks (CHOP-14; mLSG19) in patients with untreated aggressive adult T-cell leukaemia-lymphoma (ATL). To identify patients who require VCAP-AMP-VECP, we conducted a supplementary analysis of JCOG9801. Overall, 105 patients were included and categorized into low- (n = 44), intermediate- (n = 54) and high-risk (n = 7) groups according to the age-adjusted ATL prognostic index (ATL-PI). We excluded the high-risk group due to small numbers of patients. VCAP-AMP-VECP did not show any superior trend for overall survival (OS) in the low-risk group (hazard ratio: 1·04; 95% confidence interval: 0·54-2·04). Better OS was observed in the intermediate-risk group treated with VCAP-AMP-VECP (hazard ratio: 0·65; 95% confidence interval: 0·36-1·19). In the intermediate-risk group, the VCAP-AMP-VECP arm showed higher complete response rates than the CHOP-14 arm (44·0% vs. 13·8%). The VCAP-AMP-VECP arm in both risk groups exhibited grade 4 thrombocytopenia, while grade 4 neutropenia was only observed in the intermediate-risk group. VCAP-AMP-VECP remains suitable for the intermediate-risk group, whereas its benefits appear modest in the low-risk group.

Background Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML. Methods One hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation. Results GEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing. Conclusions We have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

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.

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.

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.

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

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.

Background and aim Salvage endoscopic resection (ER) is among the curative treatments for superficial local failure after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC). The present study aimed to clarify risk factors for recurrence after salvage ER. Methods This study enrolled consecutive ESCC patients treated with salvage ER for local failure after CRT between 1998 and 2013. Recurrences after salvage ER included locoregional recurrences and distant metastases. Multivariate analysis was carried out on clinicopathological parameters to identify risk factors for post-salvage ER recurrence. Results Of the 72 patients enrolled in this study, 37/8/23/4 patients had been staged before CRT as cT1/T2/T3/T4 and 44/28 patients as cN0/N1, respectively, and local failures detected before salvage ER were residual lesions after CRT in 19 and local recurrences in 53 patients. Resected specimens were classified as pT1a (M) in 45 and pT1b (SM) in 27 patients. During the median 45-month follow up (range, 3-175 months) after salvage ER, 27 (38%) patients developed recurrence with a 3-year recurrence-free survival rate of 48.9% (95% confidence interval [CI], 36.5-60.3). Multivariate analysis showed that residual lesions after CRT (HR, 2.55; 95% CI, 1.32-4.94) and lesions with a submucosal tumor (SMT)-like appearance before salvage ER (HR, 2.08; 95% CI, 1.04-4.18) were significantly associated with post-salvage ER recurrence. Conclusions Clinical findings (e.g. residual tumors found immediately after CRT and macroscopic SMT-like appearance before salvage ER) were shown to be significant risk factors for post-salvage ER recurrence.

A randomized phase III trial was initiated in Japan in August 2019 to confirm the superiority of preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy compared to the standard treatment, i.e. surgery plus adjuvant chemotherapy, for locally recurrent rectal cancer in local relapse-free survival. In all, 110 patients from 43 Japanese institutions will be recruited over a period of 6 years. Eligible patients would be registered and randomly assigned to each group with an allocation ratio of 1:1. The primary endpoint is local relapse-free survival. The secondary endpoints are overall survival, relapse-free survival, proportion of local relapse, proportion of distant relapse, proportion of patients with pathological R0 resection, response rate of preoperative chemoradiotherapy (preoperative chemoradiotherapy arm), pathological complete response rate (preoperative chemoradiotherapy arm), proportion of patients who completed the protocol treatment, incidence of adverse events (adverse reactions) and quality of life after surgery. This trial has been registered at the Japan Registry of Clinical Trial: jRCTs031190076 [https://jrct.niph.go.jp/latest-detail/jRCTs031190076] and ClinicalTrials.gov: NCT04288999 [https://clinicaltrials.gov/ct2/show/NCT04288999].

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

A randomized phase III trial in Japan commenced in June 2019. The present standard treatment for newly diagnosed glioblastoma is maximal resection followed by chemoradiotherapy with temozolomide. The purpose of this study is to confirm the superiority of maximal resection with carmustine wafer implantation followed by chemoradiotherapy with temozolomide over the standard maximal resection followed by chemoradiotherapy with temozolomide in terms of overall survival for newly diagnosed glioblastoma. A total of 250 patients will be accrued from 35 Japanese institutions in 5.5 years. Patients with >90% surgical resection will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is overall survival and the secondary endpoints are progression-free survival, loco-regional progression-free survival and incidence of adverse events. This trial has been registered in the Japan Registry of Clinical Trial, as jRCT1031190035 [https://jrct.niph.go.jp/en-latest-detail/jRCT1031190035].

Objectives Neoadjuvant chemotherapy (nCT) followed by surgery is one of the standard treatments for resectable esophageal squamous cell carcinoma (ESCC). According to the Response Evaluation Criteria in Solid Tumors, endoscopic evaluation of a primary lesion is not recommended during nCT because of reduced objectivity. This study aimed to develop and validate endoscopic evaluation criteria for nCT. Methods This study retrospectively investigated patients with T2/3 ESCC who underwent nCT followed by radical esophagectomy across two institutions (test and validation sets). We retrospectively estimated the therapeutic effect by classifying patients according to degree of tumor shrinkage (evaluated with endoscopy) as follows: marked reduction (MR), half reduction (HR), insufficient reduction (IR), and progressive disease (PD). Three endoscopists evaluated patients in the test set. Another three endoscopists evaluated patients in the validation set. We analyzed recurrence-free survival (RFS) 3 years after surgery. Results Of 129 patients in the test set, 44 had MR, 35 had HR, 44 had IR, and six had PD. The 3-year RFS rates were 55% (overall), 79% (MR), 54% (HR), 35% (IR), and 33% (PD). Of 91 patients in the validation set, 22 had MR, 49 had HR, 18 had IR, and two had PD. The 3-year RFS rates were 54% (overall), 77% (MR), 55% (HR), 22% (IR), and 50% (PD). Conclusions Our endoscopic criteria for nCT predicted prognosis; however, future studies are needed to further investigate our criteria before general application in the clinical setting.

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.

In this study, a laparoscopic imaging device and a light source able to select wavelengths by bandpass filters were developed to perform multispectral imaging (MSI) using over 1000 nm near-infrared (OTN-NIR) on regions under a laparoscope. Subsequently, MSI (wavelengths: 1000–1400 nm) was performed using the built device on nine live mice before and after tumor implantation. The normal and tumor pixels captured within the mice were used as teaching data sets, and the tumor-implanted mice data were classified using a neural network applied following a leave-one-out cross-validation procedure. The system provided a specificity of 89.5%, a sensitivity of 53.5%, and an accuracy of 87.8% for subcutaneous tumor discrimination. Aggregated true-positive (TP) pixels were confirmed in all tumor-implanted mice, which indicated that the laparoscopic OTN-NIR MSI could potentially be applied in vivo for classifying target lesions such as cancer in deep tissues.

TPS457 Background: Near Infrared Photoimmunotherapy (NIR-PIT) is a newly developed, molecular targeted cancer therapy based on conjugating a near infrared silica-phthalocyanine dye to a monoclonal antibody, which result in necrotic cell death of targeted cancer cell immediately after exposure to near infrared light. Phase IIa trial of NIR-PIT with RM-1929 (anti-EGFR antibody cetuximab conjugated to IRDye 700DX) showed a 43% objective response rate (ORR) for recurrent head and neck squamous cell carcinoma (Cognetti DM, et al.ASCO 2019 abstr 6014). Meanwhile, PD-1 blockade reverses adaptive immune resistance, resulting in activation of tumor infiltrating lymphocyte after NIR-PIT in syngeneic mouse models (Nagaya T, et al. Cancer immunology research. 2019). The objective of this study is to investigate the safety and efficacy of the NIR-PIT using ASP-1929 (analogous to RM-1929) in combination with nivolumab for advanced gastric or esophageal cancer. Methods: The study is an open-label, single-arm, single-center, Phase Ib clinical trial. Eligible patients are with unresectable esophagogastric squamous cell carcinoma or EGFR positive adenocarcinoma after standard chemotherapy. Dose escalation cohort is designed to determine the recommended dose of laser irradiation energy density in a “3+3” design (50, 75, and 100 J/cm2). Nivolumab of 240 mg on Day 1 and ASP-1929 of 640 mg/m2 on Day 8 is administered, and laser irradiation is performed under endoscopy using the laser PIT unit on Day 9. In expansion cohort, approximately 20 patients will be enrolled. The primary endpoint is proportion of incidence of dose-limiting toxicity, and the secondary endpoints are proportion of incidence of adverse events, ORR, local complete response rate, progression-free survival (PFS), local PFS, overall survival, and proportion of incidence of device malfunction. We also investigate several biomarkers using pre- and post-treatment biopsied samples. First patient will be enrolled in December 2019. Clinical trial information: JapicCTI-194969.

Standard therapy for gastric diffuse large B‐cell lymphoma (DLBCL) is considered to be chemotherapy with or without involved‐field radiation therapy. Although R‐CHOP therapy alone is widely used for DLBCL with gastric lesions (DLBCL‐GL), the outcome and incidence of treatment‐related gastric complications following R‐CHOP are not well known. This study aimed to evaluate the outcome after R‐CHOP therapy in patients with gastric DLBCL including gastric complications and to identify risk factors for the complications. Consecutive patients with newly diagnosed DLBCL‐GL treated with R‐CHOP between 2003 and 2014 were retrospectively evaluated. DLBCL‐GL was defined only when pathologically confirmed in the stomach. Of the 96 patients with DLBCL‐GL, 63 patients were diagnosed with gastric symptoms. Eighty‐eight patients (92%) completed six to eight cycles of R‐CHOP. The complete remission (CR) rate was 86%, and 3‐year and 5‐year overall survival rates were 80% and 73%, respectively. Patients were well stratified according to the Revised International Prognostic Index (R‐IPI). Complication rate was 8% (8/96); seven patients had bleeding and three had stenosis. No patients had gastric perforation. Bleeding occurred during the first cycle of R‐CHOP in five patients (5/7, 71%). Patients with gastric complications had a lower R‐CHOP completion rate (50%, P = 0.001) and a lower CR rate (25%, P

Background and objectives To clarify prognostic factors for the patients with esophageal squamous cell carcinoma (ESCC) through an assessment of surgically resected specimens modified by neoadjuvant chemotherapy (nCT). Methods We retrospectively reviewed the clinicopathological data of 143 consecutive patients with ESCC who underwent nCT followed by surgery between 2008 and 2012 at our institution and conducted survival analysis. The tumor regression grade (TRG) was classified based on the proportion of residual tumor cells in the area where the tumor was thought to have existed before nCT as follows: Grade 0 (no therapeutic effect), Grade 1a (residual tumor cells ≥2/3), Grade 1b (1/3≤ residual tumor cells

Primary adenocarcinoma arising from heterotopic gastric mucosa (HGM) is rare and the clinicopathological characteristics are not well known. We present two cases of esophageal adenocarcinoma arising from HGM with a review of a case series. Case 1 was a 78-year-old woman who underwent a periodic medical examination without complaining of any symptoms. Preoperative evaluation suggested esophageal adenocarcinoma arising from the HGM. The patient was treated with endoscopic submucosal dissection. Definitive pathological diagnosis confirmed adenocarcinoma arising from the HGM. Case 2 was a 70-year-old man who underwent a medical examination after complaining of dysphagia. Preoperative diagnosis suggested esophageal adenocarcinoma; however, its origin was unclear. The patient was treated with surgical resection. Definitive pathological diagnosis revealed adenocarcinoma arising from the HGM. In this article, the authors report the clinicopathological features of esophageal adenocarcinoma arising from HGM that were collected from a literature review and our cases.

Objectives Lymph node metastasis (LNM) in submucosal invasive esophageal squamous cell carcinoma (SM-ESCC) is a prognostic factor. The aim of this study was to identify a histopathologic predictor of LNM in SM-ESCC. Methods In total, 108 patients who underwent an esophagectomy and lymph node dissection without preoperative therapy and who were pathologically diagnosed with SM-ESCC were enrolled in this study. Relationships between several clinicopathologic factors and LNM were examined. Results A multivariate analysis revealed that a tumor size of 35 mm or more (P = .0025), submucosal invasive depth (SID) of 2,000 μm or more (P = .013), and lymphatic infiltration (P < .0001) were significant independent predictors of LNM. In addition, there were significant differences in recurrence-free survival curves between patients with SID less than 2,000 μm or not (P = .029) and tumor size less than 35 mm or not (P = .049). Conclusions This study suggests that SID may predict not only LNM but also poor prognosis.

Background and study aims: One of the major complications after endoscopic resection (ER) for large superficial esophageal squamous cell carcinoma (ESCC) is benign esophageal stricture, which can reduce quality of life even if ESCC achieves a cure without organ resection. Recently, steroid administration has been reported as a prophylactic treatment to prevent esophageal strictures. This retrospective study evaluated the stricture rate according to the different width of mucosal defects due to ER and compared it to that seen with prophylactic steroid administration. Patients and methods: Between June 2007 and December 2013, we enrolled patients with ESCC who had 3/4 or larger circumferential mucosal defects due to ER. In December 2009, steroid injections (triamcinolone acetonide 50 mg) into the ulcer bed due to ER were introduced. Beginning in November 2012, we commenced oral steroid administration (prednisolone 30 mg/day, tapered gradually for 8 weeks) in addition to steroid injection. Patients were classified into 3 groups according to the width of mucosal defect after ER (Group A, ≥ 3/4 and

AIM To identify the risk factors and clarify the subsequent clinical courses. METHODS This study retrospectively analyzed consecutive patients with esophageal squamous cell carcinoma (ESCC) treated using endoscopic submucosal dissection (ESD) between April 2008 and October 2012. We divided the ESCC lesions into perforation cases and non-perforation cases, and compared characteristics and endoscopic findings between the two groups. "Intraoperative perforation" was defined as the detection of a perforation site during ESD and the presence of mediastinal emphysema. RESULTS In total, 147 patients with 156 ESCC lesions were treated by ESD. Intraoperative perforation was recorded for nine lesions (5.8%) from nine patients. Multivariate analysis identified mucosal deficiency larger than 75% of the circumference of the esophagus as an independent risk factor for intraoperative perforation (OR = 7.37, 95%CI: 1.45-37.4, P = 0.016). The predominant site of perforation was the left wall [6/9 (67%)]. Six of nine perforation sites were successfully closed by clips during the procedures. Two of nine cases required drainage for pleural effusions; however, all nine cases recovered with conservative treatment and without surgical intervention. At the median follow up of 42 mo after ESD, no cases of local recurrence or distant organ metastasis had been observed. CONCLUSION This study suggests that mucosal deficiency larger than 75% of the luminal circumference is a risk factor for intraoperative perforation during ESD for ESCC.

Background The incidence rate has been increasing for superficial head and neck squamous cell carcinoma (HNSCC) discovered through surveillance endoscopic study using narrow band imaging (NBI), a procedure mainly used for high-risk patients with esophageal squamous cell carcinoma (ESCC). However, there are few reports on the natural history of superficial HNSCC. The aim of this retrospective study was to investigate the natural history of superficial HNSCC. Methods From January 2007 to December 2012, 535 consecutive histologically confirmed superficial HNSCCs at the oropharynx, hypopharynx, or larynx in 319 patients were detected by endoscopic surveillance examination by using NBI. Of those, 20 untreated and observed lesions fulfilled the eligibility criteria and were analyzed in this study. Results Twenty lesions from 17 patients were analyzed. All patients were men ranging from 52 to 86 years of age, with a median age of 69 years. The median endoscopic follow-up period was 20 months (range, 6–71); 17 lesions progressed in size. In this study, four patients died; the causes of death were synchronous ESCC, synchronous HNSCC, acute myocardial infarction, and unknown causes. No patient died from progression of superficial HNSCC. Conclusions Most superficial HNSCC has the potential to change progressively. Therefore, superficial HNSCC should be detected at an early stage and be treated less invasively, such as with endoscopic resection or partial resection.