Background
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.
Methods
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.
Results
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. naïve 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-naïve 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.
Conclusions
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.
Background and aims
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.
Methods
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.
Results
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.
Conclusions
MGC does not occur commonly after curative ESD of UD-EGC, and repeated ESD could contribute to stomach preservation.
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 <50%) and high‐CER (HCER; ≥50% and ≤100%). Relationships between CER and clinicopathological factors including prognosis were then examined. Multivariate analyses of 110 patients indicated that ypT3‐4 (P = .023, HR; 2.551), positive venous infiltration (P = .006, HR; 3.526), and LCER (P = .033, HR; 1.922) were independently associated with shorter recurrence‐free survival (RFS). Multivariate analyses of 43 patients with grade 0 TRG‐PT showed that ypT3‐4 (P = .033, HR; 3.397) and LCER (P = .008, HR; 3.543) were independently associated with shorter RFS. This study showed that CER was one of the prognostic factors for ESCC patients who had received nCT followed by surgery.
Tumor regression grade in lymph nodes was associated with the prognoses of esophageal squamous cell carcinoma (ESCC) patients after neoadjuvant chemotherapy (nCT). This important study shows a new predictor for ESCC patients after nCT.
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.
Abstract
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 < 0.001). There were no differences in R0 resection rate between the two groups (73% versus 52%, P = 0.057). One patient (3%) in the salvage endoscopic submucosal dissection group had perforation. The 3-year cumulative local failure rate of salvage endoscopic mucosal resection was significantly higher than that of salvage endoscopic submucosal dissection (27% versus 5%, P = 0.032). In multivariate analysis, salvage endoscopic mucosal resection (hazard ratio: 2.7, P = 0.044) was the only independent risk factor of local failure after salvage endoscopic resection.
Conclusions
Salvage endoscopic submucosal dissection is the effective treatment for local recurrence based on the short-term outcomes and local efficacy.
Salvage endoscopic submucosal dissection is the effective treatment for local recurrence after chemoradiotherapy for esophageal cancer compared with salvage endoscopic resection.
Background
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).
Methods
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.
Results
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.
Conclusions
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.
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.
Backgrounds
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.
Methods
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.
Results
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.
Conclusion
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.
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.
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.
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