Yoshinobu Yamamoto

INTRODUCTION: The optimal management of esophageal cancer with muscularis mucosae or shallow submucosal invasion (postendoscopic resection [ER] pMM/SM1 cancer) remains controversial. Evidence is largely retrospective, and prospective data are lacking. METHODS: This study enrolled patients with squamous cell carcinoma (SCC) or esophageal adenocarcinoma (EAC) diagnosed as post-ER pMM/SM1 cancer. Outcomes included overall survival, metastatic recurrence, local recurrence, and second primary esophageal cancer. RESULTS: Overall, 385 patients were enrolled, including 315 with SCC and 70 with EAC. Five-year overall survival was 92.3% (95% Confidence interval [CI], 88.8%–94.8%) for SCC and 94.2% (95% CI, 85.4%–97.8%) for EAC. Among post-ER lymphovascular invasion (LVI)-negative patients managed without additional treatment, 5-year survival rates were 94.0% (95% CI, 90.2%–96.4%) for SCC and 93.3% (95% CI, 83.5%–97.5%) for EAC. Cumulative metastatic recurrence rates for LVI-negative SCC were 6.3% (95% CI, 3.0%–12.6%) for pMM and 10.5% (95% CI, 2.6%–33.7%) for pSM1 disease, whereas corresponding rates for EAC were 2.2% (95% CI, 0.3%–13.9%) and 0.0% (95% CI could not be calculated). In LVI-negative SCC, lesion size and macroscopic appearance were independent predictors of metastatic recurrence: type 0–II lesions ≤30 mm had a low cumulative metastatic recurrence rate of 2.9% (95%CI, 1.1%–7.5%). The 5-year cumulative incidence of second primary esophageal cancer was 25.8% for SCC and 3.6% for EAC. DISCUSSION: Post-ER pMM/SM1 esophageal cancer is associated with excellent long-term survival. Surveillance is a reasonable option for many LVI-negative cases, although additional treatment may be considered for selected higher risk patients.

Objectives: Postendoscopic submucosal dissection (ESD) bleeding remains a critical concern in patients receiving antithrombotic therapy, yet the risk after esophageal ESD is poorly characterized. This multicenter retrospective study evaluated the incidence of post‐ESD bleeding and thromboembolism in patients undergoing esophageal ESD while receiving antiplatelet therapy. Methods: We analyzed 570 patients with esophageal squamous cell carcinoma treated with ESD while on antiplatelet therapy between 2017 and 2022 at 21 institutions in Japan. Patients were categorized into guideline‐based discontinuation or continuation, excluding guideline‐deviating discontinuation. The primary endpoint was the rate of post‐ESD bleeding among thienopyridine users (monotherapy or dual antiplatelet therapy; DAPT) managed with guideline‐based discontinuation. Secondary endpoints included bleeding rates according to antiplatelet regimen and thromboembolism incidence. Results: A total of 154, 41, and 375 patients received thienopyridine monotherapy, DAPT, and aspirin monotherapy, respectively. Antiplatelet therapy was continued perioperatively in 32.5%, 31.7%, and 73.1% of these groups. Post‐ESD bleeding rates were 2.3% (3/132) and 3.2% (2/63) for guideline‐based discontinuation and continuation of thienopyridine users, respectively. Bleeding rates for discontinuation vs. continuation were 0% (0/101) vs. 0.7% (2/274) for aspirin monotherapy, 1.9% (2/104) vs. 4.0% (2/50) for thienopyridine monotherapy, and 3.6% (1/28) vs. 0% (0/13) for DAPT. Thromboembolism occurred in two patients, both receiving aspirin monotherapy. Conclusions: A substantial number of patients underwent esophageal ESD while continuing antiplatelet therapy. These descriptive findings suggest a need for further evaluation of continued therapy in larger studies.

INTRODUCTION: The recommendation to discontinue low-dose aspirin (LDA) during the periprocedural period of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) remains controversial in patients at low thrombotic risk. If continuation of LDA does not increase bleeding risk, gastric ESD could be safely performed under sustained antiplatelet effects, benefiting patients. This study aimed to evaluate whether continuation of LDA is noninferior to discontinuation regarding ESD-related bleeding risk in patients with low thrombotic risk. METHODS: Patients with gastric mucosal neoplasms and low thrombotic risk who were taking LDA were eligible. Participants were randomly assigned to either the discontinuation or continuation group. No prophylaxis was performed except for cauterizing exposed vessels at the ulcer base. The primary end point was the incidence of ESD-related major bleeding. RESULTS: A total of 551 patients were enrolled. In the modified intent-to-treat analysis, the incidence of ESD-related major bleeding (95%) was 7.6% (4.8–11) in the discontinuation group (n = 276) and 10% (6.9–14) in the continuation group (n = 275), yielding a risk difference of 2.5% (−2.3 to 7.4). The upper limit of the 2-sided 90% confidence interval (6.6%) exceeded the predefined noninferiority margin (Δ5%, P = 0.157). The per-protocol analysis supported this negative result, with a risk difference of 4.4% (−0.5 to 9.5). Two patients in the continuation group developed cerebral infarction. DISCUSSION: The noninferiority of LDA continuation over discontinuation for ESD-related major bleeding in gastric ESD was not demonstrated. Therefore, discontinuation of LDA during the periprocedural period is recommended for patients with low thrombotic risk (UMIN000013177).

放射線治療後遺残再発食道癌に対する光線力学的療法（photodynamic therapy: PDT）は，光感受性物質の静脈内投与と内視鏡下のレーザー照射を組み合わせた低侵襲治療である．皮膚光線過敏症を軽減するため，2015年10月に第2世代の光感受性物質であるタラポルフィンナトリウム（レザフィリン®）が本邦で保険収載された．本稿では，放射線治療後遺残再発食道癌に対するPDTの長期成績と経過観察のポイントについて概説する．

Background: Endoscopic submucosal dissection (ESD) is widely used to treat early‐stage esophageal squamous cell carcinoma (SCC). However, the risk of recurrence in non‐curative cases remains uncertain. This study aimed to elucidate the risk of local and metastatic recurrence of esophageal SCC treated with ESD. Methods: We retrospectively analyzed data for 222 patients who underwent ESD followed by esophagectomy and fulfilled the following criteria: (1) no metastatic lesions diagnosed before ESD and (2) pathologically diagnosed SCC with SM invasion regardless of VM status or pathologically diagnosed SCC with lymphovascular invasion. The primary outcome was the proportion of metastasis and local residual cancer determined using the pathological findings of additional esophagectomy specimens and follow‐up data. Results: For submucosal cancer with positive lymphovascular invasion, the metastasis rate was 29.5% (23/78) compared with 8.8% (5/57) in submucosal cancers with negative lymphovascular invasion. The metastasis rate for vertical margin (VM) 1 or VMX was 30.8% (16/52) compared with 20.7% (28/135) in submucosal cancer. Local residual cancer was observed in 10 (19.2%) individuals with VM1/X, with 80% of these involving the submucosal layer ( n = 4) and muscularis propria or deeper ( n = 4). Among cases with VM0, local residual cancer was observed in six (3.5%) individuals, of which 66.7% were mucosal cancers. Conclusions: In conclusion, the proportions of metastasis and local residual cancer in non‐curative cases were clarified. While additional treatment is necessary to reduce these risks, if a patient is managed with observation alone, strict surveillance that accounts for these risks is required.

Esophageal stricture causes severe distress to patients; however, there are no established treatments for esophageal anastomotic strictures refractory to endoscopic balloon dilation (EBD). Steroid injection added to EBD and radial incision and cutting (RIC) are effective for such strictures, but it is unclear which is more effective. The objective of this study was to investigate the safety and efficacy of RIC plus steroid injection compared with EBD plus steroid injection for patients with refractory anastomotic strictures after esophagectomy.This was a multicenter, randomized phase II/III trial. Patients with esophageal anastomotic strictures refractory to three or more dilations were eligible. The primary endpoint in phase II was the proportion of predefined grade 3/4 adverse events (AEs). The co-primary endpoints in phase III were restricture-free survival and number of EBDs in the 24 weeks after treatment.130 patients were enrolled, with a dysphagia score of grade 2 in 104 patients (80.0%). The median number of dilations before registration was five in each arm. Predefined grade 3/4 AEs occurred in two patients (3.1%) in each arm. Restricture-free survival was 10.6 weeks (95%CI 6.9–20.1 weeks) with EBD and 8.7 weeks (95%CI 7.1–10.9 weeks) with RIC (one-sided P=0.82). The median number of EBDs in the 24 weeks after initial treatment was one (interquartile range [IQR] 0–2) for EBD and two (IQR 0–3) for RIC (one-sided P=0.99).EBD combined with steroid injection is the standard treatment for refractory anastomotic stricture after esophagectomy.

Objectives: Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) is performed for the treatment of lesions with varied backgrounds and factors. However, the predictive factors associated with the technical difficulty of ESD remain unknown in patients with varied lesions. Therefore, this study aimed to identify the predictive factors associated with the technical difficulty of ESD for ESCC using a retrospective cohort.Methods: This multicenter, retrospective study was conducted in 10 hospitals in Japan. Consecutive patients who underwent esophageal ESD between January 2013 and December 2019 were enrolled. Lesions of subepithelial tumors, adenocarcinoma, and adenoma were excluded. Difficult lesions were defined as ESD requiring a long procedure time (≥120 min), perforation development, piecemeal resection, or discontinued ESD. In the present study, the clinical factors were assessed to identify the technical difficulty of ESD using univariate and multivariate analyses.Results: Among 1708 lesions treated with esophageal ESD, eight subepithelial tumors, 44 adenocarcinomas, and two adenomas were excluded. Finally, 1505 patients with 1654 lesions were analyzed, and 217 patients with 217 lesions (13.1%) were classified as patients with difficult lesions. In multivariate analysis, the predictive factors associated with the technical difficulty of ESD were as follows: tumors with varices, tumors with diverticulum, antiplatelet use (discontinued), circumference of tumor (≥1/2), preoperative tumor size ≥30 mm, trainee, and nonhigh‐volume center.Conclusion: This multicenter retrospective study identified the predictive factors associated with the technical difficulty of ESD for ESCC with varied backgrounds and factors.

Objectives: Chemoradiotherapy (CRT) or radiotherapy (RT) alone is often the treatment of choice for elderly patients with esophageal cancer with the expectation of organ preservation. However, salvage treatment remains a problem when endoscopic resection is not indicated for local failure after CRT/RT. Photodynamic therapy (PDT) is indicated for local failure after CRT/RT, but there are few reports on its efficacy and safety in elderly patients. This study aimed to assess the outcome of PDT for local failure after CRT/RT for esophageal cancer in elderly patients.Methods: This retrospective single‐center study included 42 patients who first underwent PDT between April 2013 and June 2021. Patients aged ≥80 and <80 years were classified into the elderly and nonelderly groups, respectively. Local complete response rate, overall survival, progression‐free survival, and incidence of adverse events related to PDT were compared retrospectively between the groups.Results: The local complete response rate was 93.3% in the elderly group and 85.7 in the non‐elderly group. The 2‐year overall survival rate was 68.6% and 72.5%, and the 2‐year progression‐free survival rate was 49.5% and 70.0% in the elderly and nonelderly groups, respectively. There was no significant difference in any of these outcomes between the groups. In terms of adverse events, pneumonia and delirium tended to occur more frequently in the elderly group, but there were no serious adverse events in either group.Conclusion: The outcome of salvage PDT in the local control was comparable between the elderly and nonelderly patients for local failure after CRT/RT for esophageal cancer.