Search

Endoscopy poses a high risk of severe acute respiratory syndrome coronavirus 2 infection for medical personnel due to the dispersal of aerosols from the patient. We investigated the location and size of droplets generated during esophagogastroduodenoscopy (EGD) and endoscopic submucosal dissection (ESD), the contamination of the surrounding area before and after the procedures, and the effectiveness of using an extraoral suction device (Free arm arteo; TOKYO GIKEN, Inc., Tokyo, Japan).Patients who consented to the study and underwent EGD or ESD between December 8, 2020, and April 15, 2021, at the National Cancer Center East Hospital were included. Adenosine triphosphate (ATP) hygiene monitoring tests and a particle counter were used for measurements.Assessments were performed on 22 EGD and 15 ESD cases. ATP hygiene monitoring tests showed significant elevations at three sites near the patient, and two sites 1.5 m away, for EGD, and at four sites near the patient and 1.5 m away for ESD. In both ESD and EGD, extraoral suction devices reduced the extent of the contamination. Particles5 μm in size were generated during endoscopic procedures and dispersed from both the forceps hole and the patient's mouth. The extraoral suction device did not reduce the number of particles generated.During endoscopic procedures, cleaning the surrounding environment is important in addition to standard precautions the endoscopist and caregivers take. The use of extraoral suction devices can also potentially reduce contamination of the surrounding environment.

Preserving the colon while preventing colorectal cancer is challenging in patients with familial adenomatous polyposis. Although prophylactic colectomy is the current standard of care, some patients with familial adenomatous polyposis may wish to postpone colectomy as long as polyposis can be managed by endoscopic resection. This study examined our endoscopic management and prognostic results for patients with familial adenomatous polyposis who refused to undergo colectomy. We retrospectively analyzed the data of 12 patients with familial adenomatous polyposis treated at our hospital between January 1995 and December 2020. All patients opted to postpone prophylactic colectomy although they had significant polyp burdens and underwent endoscopic management, in which colorectal polyps sized 5 mm were thoroughly resected during baseline colonoscopies and subsequently, newly arising colorectal polyps sized 5 mm were periodically resected during surveillance colonoscopies. Patients (median age, 33 years) were followed up for a median of 5.2 years. The median number of colonoscopies and resected lesions per patient was 2 and 14 at baseline as well as, 9 and 32 during surveillance, respectively. The interval between colonoscopies was 1.0 and 7.0 months for baseline and surveillance, respectively. The colons of all 12 patients were preserved, and no invasive colorectal cancer developed. In 10 patients, 35 cases of high-grade dysplasia were observed and managed by endoscopic resection. Repeated endoscopic resection of colorectal polyps sized 5 mm with appropriate surveillance may be an alternative form of endoscopic management for patients with familial adenomatous polyposis wishing to postpone colectomy.

Endoscopic submucosal dissection (ESD) is an optimal treatment for colorectal tumors; however, it is technically difficult, especially for non-experts. Therefore, a device that helps non-experts perform colorectal ESD would be beneficial. A double-balloon endolumenal interventional platform (DEIP) was recently developed to assist colorectal ESD through endoscope stabilization and traction. This study assessed the usefulness of colorectal ESD using the DEIP (DEIP-ESD) by endoscopists, including non-experts, in a living porcine model.Two pigs were used to perform eight DEIP-ESD and eight conventional cap-assisted ESD (C-ESD) procedures. Three experts and five non-experts each resected one lesion using DEIP-ESD and one using C-ESD. We evaluated the treatment outcomes and performed stratified analyses between the experts and non-experts.Dissection speed was significantly faster in DEIP-ESD than in C-ESD (13.3 mmDEIP could facilitate colorectal ESD by improving dissection efficiency without increasing adverse events, especially when performed by non-experts.

Endoscopic resection (ER) for early gastric cancer (EGC) can preserve the stomach; however, the remaining stomach can develop second gastric cancer. Few reports have prospectively investigated the incidence and treatment outcomes of second gastric cancer.This post-hoc analysis used the dataset of the single-arm confirmatory trial, JCOG0607. The key inclusion criteria for JCOG0607 were solitary differentiated-type EGC and no previous gastrectomy or endoscopic treatment for EGC. Three hundred seventeen patients who underwent curative ER were included in this study. Surveillance endoscopy was performed 1 to 3 months after the initial ER and subsequently annually for at least 5 years. A lesion detected ≤1 year and1 year after the initial ER was defined as overlooked gastric cancer (OGC) and metachronous gastric cancer (MGC), respectively.During a median follow-up period of 6.0 years (interquartile range, 5.1-7.0), 30 OGCs and 61 MGCs were detected in 24 and 48 patients, respectively. The cumulative incidence of OGC at 1 year and MGC at 5 years was 7.6% and 12.7%, respectively. ER and gastrectomy were performed in 85 lesions and 6 lesions, respectively. Pathologic evaluation showed 78 mucosal cancers, 12 submucosal cancers, and 1 advanced cancer. Eventually, 28 OGCs and 52 MGCs fulfilled the pathologic criteria for curative ER.Our study was the first to reveal the actual incidence of second gastric cancer after curative ER for differentiated-type gastric cancer. Most lesions could be treated with ER. Continuous endoscopic surveillance after curative ER is important to detect second gastric cancer.

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

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

Background 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.

The multi-institutional, single-arm, confirmatory trial (JCOG0607) showed excellent efficacy of endoscopic submucosal dissection (ESD) for the expanded indication of intramucosal intestinal-type early gastric cancer (EGC), which consists of two groups; the lesions 2 cm if clinical finding of ulcer (cUL)-negative or those ≤ 3 cm if cUL-positive because of the expected low risk of lymph node metastasis. However, the proportion of non-curative resections (NCR) requiring additional surgery was high (32.4%). This post hoc analysis aimed to explore the clinical factors associated with NCR.As the expanded indication includes two different groups, we explored the clinical factors associated with NCR separately in cUL-negative ( 2 cm) and cUL-positive (≤ 3 cm) groups using the log-linear model.Two hundred sixty cUL-negative and 206 cUL-positive EGCs were analyzed. The proportions of NCR were 33.8% in the cUL-negative group and 29.6% in the cUL-positive group. A multivariable analysis demonstrated that moderately differentiated predominant histology diagnosed in pre-treatment biopsy (risk ratio (RR), 1.93, 95%CI 1.34-2.77, P0.001) and lesion in the upper stomach (RR, 1.75, 95%CI 1.03-2.96, P=0.038) in the cUL-negative EGCs, and tumor size 2 cm (RR, 1.78, 95%CI 1.22-2.58, P=0.003) and female sex (RR, 1.62, 95%CI 1.07-2.44, P=0.021) in the cUL-positive EGCs were independent factors associated with NCR.Clinical risk factors associated with NCR were different between cUL-negative and cUL-positive EGCs. To avoid NCR, we need to take these factors into account when deciding expanded indication for ESD.

Background Improvements in early detection and treatment have resulted in an increasing number of long-term survivors of colorectal cancer (CRC). For the survivors, second primary cancer and recurrence are important issues; however, evidence for an appropriate surveillance strategy remains limited. This study aimed to investigate the frequency and timing of second primary cancer in patients after surgery for exploring an appropriate surveillance strategy by using an integrated analysis of three large-scale randomized controlled trials in Japan. Methods The eligibility criteria of three trials included histologically confirmed CRC and having received surgery. The timing, site and frequency of second primary cancers and recurrence were investigated. Risk factors associated with second primary cancers were also examined. The standardized incidence ratio (SIR) of second primary cancers compared with the national database of the Japan Cancer Registry was estimated. Results A total of 2824 patients were included in this study. The cumulative incidence of second primary cancer increased over time. The SIR of any second primary cancer was 1.07 (95% CI: 0.94–1.21). The SIR for second primary cancers of colon was 1.09 (95% CI: 0.79–1.47). The cumulative incidence of recurrence almost reached plateau at 3 years. Conclusions A common surveillance strategy for the general population can be applied even for curatively resected CRC patients, as the risk of second primary cancers was almost the same as that of the general population.

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.

Salvage endoscopic therapy, including endoscopic resection (ER) and photodynamic therapy (PDT), is effective for esophageal squamous cell carcinoma (ESCC) in local failure after chemoradiotherapy (CRT). Resection with pathologically vertical margin-negative (VM0) for ER and local complete response (L-CR) for PDT are important surrogate prognostic markers for each therapy's efficacy. We aimed to evaluate the usefulness of endoscopic ultrasound (EUS) in predicting the efficacy of salvage endoscopic therapy in local failure after CRT for ESCC.We included patients who underwent EUS followed by ER or PDT for local failure after CRT or radiotherapy for ESCC from 2006 to 2020. We evaluated EUS findings associated with VM0 resection for ER and L-CR for PDT, which included the status of the outermost part of the submucosal layer, tumor thickness, and tumor invasion length into the muscularis propria (MP) layer.Thirty and 47 patients were enrolled into the ER and PDT groups, respectively. The VM0 resection rate in the ER group was 87% (26/30). The EUS findings associated with VM0 resection were tumor thickness 2.3 mm (p = 0.01) and preserved hyperechoic line of the outermost part of the submucosa layer (p 0.01). The L-CR rate in the PDT group was 69% (32/47). The EUS findings associated with L-CR were tumor thickness 5.0 mm (p 0.01) and tumor invasion length into the MP layer 1.6 mm (p = 0.03).EUS can be useful in predicting the efficacy of salvage endoscopic treatment for local failure after CRT for ESCC.

Objectives Salvage endoscopic resection is recommended when the local recurrence at primary site after chemoradiotherapy for esophageal squamous cell carcinoma is localized and superficial. This retrospective study aimed to comparatively analyse the short-term outcomes and local control of salvage endoscopic submucosal dissection versus salvage endoscopic mucosal resection for local recurrence after chemoradiotherapy or radiotherapy. Methods A total of 96 patients who underwent initial salvage endoscopic resection for cT1N0M0 local recurrence after chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma between December 1998 and August 2019 patients were assigned to either the salvage endoscopic submucosal dissection (40 patients; 40 lesions) or salvage endoscopic mucosal resection (56 patients; 56 lesions) group. We evaluated the en bloc and R0 resection rates, severe adverse events and local failure rate after salvage endoscopic resection. Multivariate analysis was conducted to identify risk factors of local failure after salvage endoscopic resection. Results The en bloc resection rate was significantly higher in the salvage endoscopic submucosal dissection group than in the salvage endoscopic mucosal resection group (95% versus 63%; P Conclusions Salvage endoscopic submucosal dissection is the effective treatment for local recurrence based on the short-term outcomes and local efficacy.

Recently, the JCOG0502 has shown a comparable efficacy of chemoradiotherapy and esophagectomy in patients with clinical T1N0M0 esophageal squamous cell carcinoma. However, few studies have compared the clinical outcomes of these treatments in esophageal squamous cell carcinoma patients (including elderly patients) based on real-world data.This retrospective study determined real-world outcomes in patients who underwent chemoradiotherapy or esophagectomy, including those with clinical T1N0M0 esophageal squamous cell carcinoma, between 2009 and 2017 at the National Cancer Center Hospital East.Among a total of 156 patients, 120 and 36 patients underwent esophagectomy and chemoradiotherapy, respectively; 138, 12 and 6 patients had Eastern Cooperative Oncology Group performance status 0, 1, and 2, respectively; and 33 and 123 patients had clinical tumor depth MM-SM1 and SM2-SM3, respectively. In a median follow-up of 72 months, 5-year progression-free survival and overall survival were respectively 77.0% and 81.5% in the esophagectomy group and 74.4% and 82.6% in the chemoradiotherapy group (P = 0.48 and, P = 0.89). Moreover, no treatment-related death was detected in both groups. In elderly patients (75 years or older), 5-year progression-free survival and overall survival were not significantly different between esophagectomy and chemoradiotherapy groups (5-year progression-free survival: 72.3% vs. 81.8%, P = 0.38; 5-year overall survival: 76.9% vs. 81.8%, P = 0.59).This real-world study confirms the results of a previous clinical trial, and the present findings support chemoradiotherapy as one of the standard treatment options in patients of all ages with clinical T1N0M0 esophageal squamous cell carcinoma.

Although salvage endoscopic resection is an optimal treatment for local failure after chemoradiotherapy for esophageal squamous cell carcinoma, recurrent metastasis (lymph node and/or distant metastasis) after salvage endoscopic resection may occur with a certain degree of unavoidable frequency and is associated with a poor prognosis. However, the risk factors for recurrent metastasis are unclear. This study aimed to evaluate the risk factors for recurrent metastasis after salvage endoscopic resection.Patients who underwent salvage endoscopic resection for local failure after chemoradiotherapy/radiotherapy were analyzed in this single-center, retrospective study. We evaluated the cumulative incidence rates of recurrent metastases, overall survival, and the risk factors for recurrent metastasis after salvage endoscopic resection.We analyzed 132 patients. The 5-year cumulative incidence rate of recurrent metastases after salvage endoscopic resection was 25.7%. The 5-year overall survival rates in all patients and in patients with recurrent metastasis were 66.8% and 22.5%, respectively. Local failure pattern with a residual lesion after chemoradiotherapy/radiotherapy (subdistribution hazard ratio 2.34; P = 0.012) and the presence of lymphatic invasion in salvage endoscopic resection specimen (subdistribution hazard ratio 3.20; P = 0.002) were significant risk factors for recurrent metastasis.Patients with local failure pattern with a residual lesion after chemoradiotherapy/radiotherapy and presence of lymphatic invasion have a high risk for recurrent metastasis. Thus, appropriate surveillance for these patients should be considered.

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

OBJECTIVES S-1 monotherapy with concurrent radiotherapy (RT) is a standard of care for patients with locally advanced pancreatic cancer (LAPC). Although renal dysfunction increases S-1 monotherapy toxicity, its effect in S-1 with concurrent RT remains unknown. We evaluated the effect of renal function on the safety of S-1 with RT for LAPC. METHODS We performed an integrated exploratory post hoc analysis of data from 2 prospective studies (JCOG1106 and LAPC-S1RT), where patients with LAPC received RT (50.4 Gy/28 fraction for 5.5 weeks) and concurrent S-1 (40 mg/m2 per dose, twice daily on the day of irradiation). We split the patients into high creatinine clearance (CCr; ≥80 mL/min) and low CCr (

Background Previous studies have suggested that patients with esophageal squamous cell carcinoma (ESCC) are still at a high risk of developing second primary malignancies (SPMs) after definitive therapies. We evaluated the development of SPMs and explored its risk factors in patients with clinical T1bN0 ESCC. Methods JCOG0502 prospectively compared esophagectomy with definitive chemo-radiotherapy for clinical T1bN0 ESCC. Here, we reviewed all JCOG0502 patients’ data for SPMs and investigated the risk factors for SPMs using uni-variable and multivariable analyses by Fine and Gray model. Results Among 379 enrolled patients, 213 underwent esophagectomy and 166 received chemo-radiotherapy. Patient characteristics were male (85%); median age [63 (range 41–75) years; location of the primary tumor (upper/middle/lower thoracic esophagus, 11%/63%/27%, respectively]; alcohol consumption history (79%); smoking history (66%); prevalence of no/several/many/unknown Lugol-voiding lesions (LVLs) (45%/36%/8%/11%, respectively). In a median follow-up of 7.1 years, 118 SPMs occurred in 99 (26%) patients. Cumulative incidences of SPMs after 3, 5, and 10 years were 9%, 15%, and 36%, respectively. The most common primary tumor sites were the head and neck (35%), stomach (20%) and lungs (14%). In multivariable analyses, compared to no LVLs, several LVLs [hazard ratio (HR) 2.24, 95% confidential interval (CI) 1.32–3.81] and many LVLs (HR 2.88, 95% CI 1.27–6.52) were significantly associated with the development of SPMs. Sixteen patients died due to the SPMs. Conclusion The incidence of SPMs was high. The presence of LVLs, which was a predictive factor for SPMs, may be useful for surveillance planning.

The traction assisted (TA) method has reduced the technical difficulty associated with esophageal endoscopic submucosal dissection (ESD). However, it is unclear which factors associated with difficulty have been improved by the TA-ESD method. We aimed to evaluate and compare difficulty factors between conventional and TA-ESD.We retrospectively enrolled patients treated by ESD from Apr 2010 to Jun 2014 for the conventional ESD cohort and from Jan 2016 to Dec 2019 for the TA-ESD cohort. Difficult cases were defined as; (1) ≥ 120 min ESD procedure time, (2) intraoperative perforation, or (3) piecemeal resection. We explored and compared the factors associated with technical difficulty in each cohort.The conventional and TA-ESD cohorts included 285 (299 lesions) and 387 (421 lesions) patients, respectively. For difficult cases, the conventional and TA-ESD cohorts had 91 (30%) and 71 (17%) lesions, respectively. Multivariate logistic regression showed that ≥ 30 mm lesion length (odds ratio (OR) 6.85, 95% confidence interval (CI) 3.47-13.50), lower esophagus (OR 2.37, 95% Cl 1.34-4.21), 1/2 circumference (OR 2.26, 95% CI 1.28-3.99), and left wall (OR 2.72, 95% CI 1.42-5.20) in the conventional ESD cohort, and ≥ 30 mm lesion length (21.30, 95% CI 4.75-95.30), lower esophagus (OR 3.05, 95% CI 1.52-6.13), and 1/2 circumference (OR 6.40, 95% CI 3.06-13.40) in the TA-ESD cohort, were independently associated with technical difficulty.TA-ESD can reduce the difficulty in cases including lesions in the left wall; however, cases in the lower esophagus and large lesions were still difficult to simplify.

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

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

Background Recently, the JCOG0502 has shown a comparable efficacy of chemoradiotherapy and esophagectomy in patients with clinical T1N0M0 esophageal squamous cell carcinoma. However, few studies have compared the clinical outcomes of these treatments in esophageal squamous cell carcinoma patients (including elderly patients) based on real-world data. Methods This retrospective study determined real-world outcomes in patients who underwent chemoradiotherapy or esophagectomy, including those with clinical T1N0M0 esophageal squamous cell carcinoma, between 2009 and 2017 at the National Cancer Center Hospital East. Results Among a total of 156 patients, 120 and 36 patients underwent esophagectomy and chemoradiotherapy, respectively; 138, 12 and 6 patients had Eastern Cooperative Oncology Group performance status 0, 1, and 2, respectively; and 33 and 123 patients had clinical tumor depth MM-SM1 and SM2-SM3, respectively. In a median follow-up of 72 months, 5-year progression-free survival and overall survival were respectively 77.0% and 81.5% in the esophagectomy group and 74.4% and 82.6% in the chemoradiotherapy group (P = 0.48 and, P = 0.89). Moreover, no treatment-related death was detected in both groups. In elderly patients (75 years or older), 5-year progression-free survival and overall survival were not significantly different between esophagectomy and chemoradiotherapy groups (5-year progression-free survival: 72.3% vs. 81.8%, P = 0.38; 5-year overall survival: 76.9% vs. 81.8%, P = 0.59). Conclusions This real-world study confirms the results of a previous clinical trial, and the present findings support chemoradiotherapy as one of the standard treatment options in patients of all ages with clinical T1N0M0 esophageal squamous cell carcinoma.

Objectives Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers. Methods Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy. Results A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of Conclusions This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate.

A randomized phase III trial commenced in Japan in February 2018. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced unresectable esophageal carcinoma. The purpose of this study is to confirm the superiority of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) followed by conversion surgery or definitive CRT over definitive CRT alone for overall survival (OS) in patients with locally advanced unresectable squamous-cell carcinoma of thoracic esophagus. A total of 230 patients will be accrued from 47 Japanese institutions over 4.5 years. The primary endpoint is OS, and the secondary endpoints are progression-free survival, complete response rate of CRT, response rate of DCF, adverse events of DCF and CRT, late adverse events and surgical complications. This trial has been registered at the Japan Registry of Clinical Trials as jRCTs031180181.

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.