Introduction

Esophageal granular cell tumors (GCTs), the second most common subepithelial tumors (SETs) of the esophagus, are potentially malignant. Currently, no definite management guidelines exist, despite endoscopic resection being a valuable treatment option.

Aims & Methods

We evaluated the clinical outcomes of different methods of endoscopic resection of esophageal GCTs.
A total of 35 patients with endoscopically resected esophageal GCTs were retrospectively enrolled between December 2008 and October 2021. Several modified endoscopic mucosal resections (EMRs) were performed for treating esophageal GCTs. Clinical and endoscopic outcomes including complete histologic resection rate, and associated postoperative complications, were evaluated.

Results

The mean age of the 35 patients with endoscopically resected esophageal GCTs was 55.8 ± 8.2; the majority were men (57.1%). Mean tumor size was 7.2 mm ± 2.6, most (80.0%) were asymptomatic and present in the distal third of the esophagus (77.1%). Endoscopic characteristics predominantly included broad-based (85.7%) and whitish-to-yellowish color changes (97.1%). Endoscopic ultrasound (EUS) of 82.9% of the tumors revealed homogeneous hypoechoic SETs originating from the submucosa. The five endoscopic treatment methods used were: ligation-assisted (77.1%), conventional (8.7%), cap-assisted (5.7%), and underwater (5.7%) EMRs and ESD (2.9%). Mean surgery time was 6.6 minutes ± 2.1, and no procedure-associated complications were noted. The en-bloc and complete histologic resection rates were 100% and 94.3%, respectively. No local recurrences were evident during follow-up, and no significant differences in the clinical outcomes of the different methods of endoscopic resection were found.

Conclusion

Based on tumor characteristics and therapeutic outcomes, modified EMR methods can be effective and safe. However, there were no significant differences in the clinical outcomes of the different methods of endoscopic resection.

Introduction

In Japan, the standard treatment for resectable locally advanced esophageal squamous cell cancer (ESCC) is neoadjuvant triplet chemotherapy (fluorouracil, cisplatin, and docetaxel [DCF]) followed by surgery, based on the results of the phase III randomized controlled study (JCOG1109). Some reports suggest that preoperative endoscopic evaluation of the primary tumor may predict postoperative outcomes. Given the increasing importance of endoscopic evaluation of response to neoadjuvant therapy in primary tumor, the 12th edition of the Japanese Classification of Esophageal Cancer introduced a new endoscopic sub-classification “RR (Remarkable Response)”, which was defined as showing remarkably shrink to nearly T1 depth after treatment. However, its clinical significance remains unclear.

Aims & Methods

The aim of this study is to determine the clinical significance of a new endoscopic sub-classification “RR” by evaluating its association with both histological response in surgical specimens and postoperative prognosis. We retrospectively analyzed the patients with resectable locally advanced ESCC (cT2-3/N0-3/M0-1, UICC-TNM 8th edition) who were performed with ≥1 cycle of neoadjuvant DCF therapy followed by surgery at our institution between April 2015 and March 2020. Exclusion criteria were: 1) JCOG1109 participants, 2) not evaluated the primary lesion by endoscopy before or after DCF therapy due to esophageal stricture, 3) >56 days from DCF therapy completion to surgery, or 4) pathologically non-curative resection (R1-2). Two endoscopists retrospectively evaluated pre- and post-DCF therapy endoscopic images with masked prognostic information and classified the cases into three groups: 1) RR, 2) non-RR and 3) PD (Progressive disease). Histological response data were retrospectively collected from medical records. According to the 12th edition of the Japanese Classification of Esophageal Cancer, all surgically resected specimens containing visible primary tumor tissue underwent histological examination in cases where preoperative treatment has been administered. Histological response was graded according to the Japanese Classification of Esophageal Cancer, on a four-point scale ranging from grade 0 (ineffective) to grade 1 (slightly effective), grade 2 (moderately effective), and grade 3 (markedly effective). We evaluated the proportions of cases achieving histological response of grade 2-3 in each group, and also calculated 3-year RFS and OS rates in each group.

Results

Of 114 eligible patients (median age 66.5 years [range 42-76], 91 males), clinical stage distribution was IIB/IIIA/IIIB/IVA/IVB: 1/0/58/15/40. 97/0/17 patients received 3/2/1 cycles of neoadjuvant DCF therapy. By endoscopic evaluation, 63 patients were classified as RR, 51 as non-RR, and 0 as PD. Among RR cases, 45 patients (71.4%) showed histological response of grade 2-3, while among non-RR cases, 5 patients (9.8%) showed grade 2-3. During the median follow-up of 42.6 months, 3-year RFS rates for RR/non-RR groups were 62.2%/49.0% (P=0.098), and 3-year OS rates were 76.9%/53.0% (P=0.026).

Conclusion

The newly introduced “RR (Remarkable Response)” of sub-classification for endoscopic evaluation after neoadjuvant chemotherapy may be useful for predicting histological response and stratifying prognosis in locally advanced ESCC.

Introduction

Endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) is one of the most challenging endoscopic procedures due to the high risk of bleeding and fibrosis caused by prior treatment of varices. However, due to the small number of such cases, the clinical outcomes of ESD for ESCC with EVs have been reported in only a limited number of cases at single centers^​1-3.

Aims & Methods

We conducted a multicenter, retrospective, cohort study to clarify the safety and efficacy of ESD for ESCC with EVs.Eleven institutions in the Tohoku region of Japan participated in this multicenter, collaborative, retrospective study. We performed endoscopic resection for 3619 patients with esophageal carcinoma at the participating institutions during the period from January 2010 to April 2022. Among those, 30 patients who underwent ESD for ESCC with EVs were recruited for the present study.
Rates of en bloc resection and R0 resection, procedure time and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD.

Results

Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 minutes. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC.

Conclusion

This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

References

1. Sawaguchi M, Jin M, Matsuhashi T, et al. The feasibility of endoscopic submucosal dissection for superficial esophageal cancer in patients with cirrhosis (with video). Gastrointest Endosc 2014;79:681-5.
2. Choi YK, Noh JH, Kim DH, et al. Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis. Clin Endosc 2022;55:381-9.
3. Zhang S, Liu YD, Chai NL, et al. Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with esophagogastric varices: Ten-year experience from a large tertiary center in China. Gastrointest Endosc 2023 Online ahead of print.

Disclosure

The authors declare that they have no conflicts of interest.

Introduction

Endoscopic resection (ER) is widely accepted as the standard treatment for superficial esophageal squamous cell carcinoma (ESCC). In contrast, many old patients, especially 80 years or older, may die as a result of other diseases soon after ER. Therefore, the investigation of clinical outcomes and identification of prognostic factors of patients 80 years or older undergoing ER are clinically important because these findings may inform decision-making regarding the suitability of ER.

Aims & Methods

This study aimed to identify such clinical outcomes and prognostic factors. We retrospectively evaluated the short and long-term outcomes and prognostic factors of 87 patients 80 years or older undergoing ER for ESCC at two cancers between April 2012 and March 2021. We also evaluated the relationships of patient characteristics (sex, age, Eastern Cooperative Oncology Group-performance status; ECOG-PS, American Society of Anesthesiologists physical status; ASA-PS, prognostic nutritional index; PNI, Charlson comorbidity index; CCI) and overall survival rate using the Kaplan-Meier method and a Cox proportional hazards regression model.

Results

The median age of the patients was 82 years, and male was 76 patients (87.4%). The background factors were ECOG-PS 0-1 in 81 patients (93.1%) and a median CCI of 3. As short-term outcomes, 79 patients (90.8%) were curative resections (pT1a-M, V0 and Ly0), 9 patients (10.3%) had adverse events occurred (pneumonia was the most common: 4.6%), and no treatment-related deaths occurred. As long-term outcomes, 34 patients died; however, only two patients died due to ESCC. The 3-year overall survival rates and the 5-year overall survival rates were 81.4% and 71.6%, respectively. CCI≥4 (hazard ratio 4.75, 95% CI: 2.03-11.10) was identified as an independent prognostic factor.

Conclusion

The short-term outcomes were good. In contrast, as the long-term outcomes, the overall survival rates of patients with CCI≥4 were poor. The decision to perform ER for patients with CCI≥4 should be carefully considered because follow-up without ER is possible.

Introduction

Endoscopic resection (ER) of duodenal tumors carries a high risk of intraoperative or delayed perforation because of the thin duodenal wall and exposure to bile and pancreatic juice. Delayed perforation can particularly cause serious condition due to the leakage of the digestive fluids. The detailed management and clinical course following duodenal perforation remains unclear. This study aimed to clarify the optimal management of duodenal perforation following ER.

Aims & Methods

This single-center retrospective study included cases of perforation among patients who underwent ER for duodenal tumors at our institution between April 2013 and October 2024. The study endpoint was the clinical course after perforation, including the hospitalization period after ER for duodenal tumors. Perforation was defined as the presence of extraluminal gas on computed tomography (CT) scan. Delayed perforation was defined as a perforation that was not endoscopically recognized during the procedure but was diagnosed postoperatively. In contrast, intraoperative perforation was defined as a case in which a perforation was endoscopically identified during the endoscopic procedure. Long hospitalization was defined as a hospital stay of 20 days or longer.

Results

Of the 1,475 cases with duodenal tumors underwent ER during the study period, intraoperative perforation occurred in 8 cases (0.5%) and delayed perforation in 10 cases (0.7%). The median age of patients with perforation was 62 (range: 47–80) years, and 50% (9 patients) were male. The 18 cases included 6 cases of endoscopic papillectomy (EP), 7 cases of endoscopic mucosal resection (EMR), 2 cases of endoscopic submucosal dissection, and 3 cases of endoscopic submucosal resection with a ligation device. Among the cases of intraoperative perforations, long hospitalization, 61 days of conservative treatment, was required in one case who developed a large perforation during scope insertion of single‑balloon enteroscopy for duodenal adenoma resection. The remaining 7 cases achieved successful endoscopic closure intraoperatively and hospitalization periods were within 17 days. Of the 10 delayed perforation cases, 2 occurred after EP and 8 after EMR for non-ampullary tumors. The median time from the end of endoscopic resection to the diagnosis of perforation was 24 hours (4–46 hours). The median hospitalization period of the cases with delayed perforations was 32 days (9–81 days), and significantly longer than that of intraoperative perforation (13 days) (p<0.05). Long hospitalization was required in 8 cases (80%) of delayed perforation. None of the delayed perforation cases required surgical intervention, and endoscopic nasobiliary and nasopancreatic duct drainage (ENBPD) was performed in 7 cases (70%). Ascites was observed on CT scan at the time of diagnosis of delayed perforation in 7 of the 8 patients who required long hospitalization. One case without ascites at the diagnosis of delayed perforation still required long hospitalization, possibly due to the 10-hour delay from the diagnosis to ENBPD. On the other hand, two cases who did not need long hospitalization showed no ascites at the diagnosis of delayed perforation.

Conclusion

Compared to intraoperative perforation, delayed perforation was associated with significantly prolonged hospitalization, particularly in cases with ascites. Early detection of ascites and prompt initiation of ENBPD may help mitigate the clinical burden. Establishing an emergent backup system for ENBPD is essential for the safe management of delayed perforation after duodenal ER.

Introduction

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy often detected through surveillance esophagogastroduodenoscopy (EGD). Despite regular screening, some cases still progress to advanced stages, including invasion into the muscularis mucosa (pT1a-MM) or deeper layers. The detection of interval ESCC during surveillance presents a clinical challenge, as these lesions can impact long-term prognosis.

Aims & Methods

This study aimed to investigate the characteristic endoscopic features and prognosis of post-EGD ESCC (PEESCC), defined as ESCC that progressed to pT1a-MM or deeper within two years of a prior surveillance EGD that did not identify neoplasia or carcinoma. We retrospectively analyzed 225 superficial ESCC lesions from 215 patients treated with endoscopic submucosal dissection (ESD) at the Hiroshima University Hospital between April 2010 and March 2023. Among them, 29 lesions in 28 patients were classified as the post-EGD ESCC (PEESCC) group, defined as cases where EGD performed 24 months before diagnosis did not detect neoplasia or carcinoma. The remaining 196 lesions in 188 patients were the control group. Subsequently, endoscopic findings [the presence of multiple Lugol-voiding lesions (LVLs), cancer location, circumferential involvement, direction, tumor size, macroscopic type, submucosal tumor (SMT)-like elevation, tumor color, intrapapillary capillary loop (IPCL), and clinical depth of invasion] and prognosis were compared. For accurate endoscopic findings and prognostic evaluation, patients with concurrent pT2 or deeper ESCC, those who had undergone treatment for pT2 or deeper ESCC, and those with a history of esophagectomy were excluded.

Results

In the PEESCC group, the proportions of cases with the presence of multiple-LVLs (69.0% vs. 39.3%, p < 0.01), cervical esophageal lesions (17.2% vs. 3.1%, p < 0.01), lesions localized between the 11 o’clock and 1 o’clock positions (20.7% vs. 7.7%, p = 0.037), and SMT-like marginal elevations (20.7% vs. 7.7%, p = 0.037) were significantly higher, whereas the proportion of red-colored lesions (24.5% vs. 44.9%, p = 0.027) was significantly lower compared to the control group. Additionally, the tumor size in the PEESCC group was significantly smaller than that in the control group (21.6±12.3 mm vs. 34.0±18.3 mm, p<0.01). From the multivariate analysis using the stepwise method, the presence of multiple-LVLs (OR=3.2, 95%CI:1.3-8.5, p<0.01), cervical esophageal lesions (OR=9.9, 95%CI:2.2-45.6, p<0.01), small tumor diameter(≦30mm)(OR=3.3, 95%CI:1.2-10.6, p=0.017), and SMT-like elevation (OR=3.8, 95%CI:1.1-12.0, p=0.034) were significanty identified as characteristic endoscopic findings of PEESCC. No statistically significant findings were detected in the multivariate analysis of patients without ESD history. But in the multivariate analysis limited to non-CRT cases to exclude the influence of CRT, the presence of multiple-LVLs (OR=6.5, 95%CI:2.1-23.4, p<0.01), cervical esophageal lesions (OR=15.7, 95%CI:3.1-86.8, p<0.01), tumor circumferential involvement: <1/3(OR=8.5, 95%CI:1.6-46.1, p=0.013), and SMT-like marginal elevation(OR=6.5, 95%CI:0.8-9.8, p=0.015) were identified as independent risk factors for PEESCC.The PEESCC group had a lower 5-year disease-specific survival (93.1% vs. 98.5%, p=0.039) and recurrence-free survival (69.0% vs. 83.7%, p=0.0245).

Conclusion

PEESCC lesions are associated with distinct endoscopic features and poor prognosis than non-PEESCC lesions.