Introduction

In recent years, there have been reports about the risk of infection with multidrug-resistant bacteria via duodenoscopes¹, as well as the outbreak of COVID-19, which has brought attention to endoscope-mediated infections. In response, disposable endoscopes have been developed and marketed worldwide. While there have been several reports on the feasibility of disposable endoscopes for screening or emergency examinations^2,3, there are no reports on the feasibility of Endoscopic Submucosal Dissection (ESD), which requires a variety of operations with different devices.

Aims & Methods

The aim of this study was to compare the performance of disposable and reusable endoscopes in using the ESD training model (G-master, KOTOBUKI Medical), which can simulate various parts of the stomach.
ESD was performed on pseudo lesions (size: 25 mm) at the 6 simulated locations on the ESD training model using the disposable endoscope (Ambu aScope Gastro, Ambu) and the reusable endoscope (GIF-Q260J, Olympus). A total of 24 lesions were treated by 3 ESD beginners (less than 30 ESD experience) and 3 ESD experts (over 300 ESD experience), each performing on 2 locations (4 lesions).
We evaluated procedure time, dissection speed, en bloc resection rate, perforation rate, scope malfunction rate, and number of scope removals during procedure. Additionally, we administered questionnaires to assess the endoscopists' opinions on each scope, including image visibility, manipulate handle operability, tip lens washing function, the ability of device insertion and removal, and scope operability at each site, rated on a scale of 0-5. The evaluations were classified as low (<2), moderate (2<= and <4), and high (4<=).

Results

All procedures were completed using the assigned scopes. The median procedure time was 24.2 min (range, 14.2-36.5) for the disposable endoscopes (Dispo), slightly longer than 19.6 min (range, 13.5-29.5) for the reusable endoscopes (Reuse). The median dissection speed was 20.3 mm²/min (range, 13.5-34.6) for Dispo and 25.2 mm²/min (range, 16.7-36.3) for Reuse, and the differences were not significant in both (procedure time: p-value=0.284, dissection speed: p=0.379). In the subgroup analysis, Dispo tended to have slightly longer procedure time than Reuse in beginner group (Dispo: 29.5 min [range, 20.0-36.5], Reuse: 25.2 min[range, 16.3-29.5], p=0.206). On the other hands, in expert group there was almost no difference in treatment time (Dispo: 16.4 min [range, 14.2-25.2], Reuse: 16.6 min [range, 13.5-21.1], p=0.453). The en bloc resection rate was 100%, not only for Reuse but also for Dispo. No cases of perforation or scope malfunction were observed in any of the scopes. For either scope, there were no lesions that required removal of the scope due to wiping the adhesion at the tip lens or any other reasons.
The results of the questionnaires were as follows image visibility: Dispo 2.3±0.9, Reuse 4.0±0.6; manipulate handle operability: Dispo 3.5±0.8, Reuse 4.5±0.5; tip lens washing function: Dispo 3.2±1.1, Reuse 3.8±0.9; the ability of device insertion and removal: Dispo 3.3±0.5, Reuse 3.7±0.5; scope operability (evaluated at each site): Dispo 3.3±0.8, Reuse 3.9±0.5. The scores of all items for Dispo were slightly lower than those for Reuse, particularly in terms of screen visibility and usability, but scored moderately well in all categories.

Conclusion

In the training model, the performance of the disposable endoscope in the ESD procedure was acceptable compared to the reusable endoscope. As a next step, we are planning to conduct clinical research.

References

1. U.S. Food and Drug Administration. Infections Associated with Reprocessed Duodenoscopes
2. Han.ZL, et al. Evaluation of a novel disposable esophagogastroduodenoscopy system in emergency, bedside, and intraoperative settings. DEN. 11 March 2023: Online ahead of print.
3. Luo.X, et al. Disposable versus reusable gastroscopes: a prospective randomized noninferiority trial. Gastrointest Endosc. 2022 Aug;96(2):250-261.

Disclosure

This research was conducted with a research fund and disposable scopes from Ambu, and with items related to ESD training model from KOTOBUKI Medical.

Introduction

Esophageal squamous cell carcinoma (ESCC) often develops the synchronous or metachronous multiple ESCC. Although the Japanese guideline recommended endoscopic examination as surveillance at least once a year after endoscopic resection (ER) of ESCC, the optimal surveillance modality was not specified. In clinical practice, image-enhanced endoscopy (IEE) followed by Lugol chromoendoscopy (LCE) is commonly performed. While LCE reduces the proportion of missed lesion, it has low specificity and causes severe discomfort to the patients, so attempts have been made to omit Lugol's staining. It is unknown what lesions may be missed at this time point by omitting LCE in surveillance after esophageal ER.

Aims & Methods

Thus, this study aimed to clarify clinicopathological characteristics of synchronous or metachronous multiple ESCCs missed by IEE but detected by LCE in surveillance endoscopy after esophageal ER. We retrospectively analyzed the consecutive lesions that fulfilled all of the following inclusion criteria: (1) treated with endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) at our institution between April 2021 and March 2022; (2) newly detected during surveillance endoscopy after ER or during preoperative endoscopy for other ESCC; (3) underwent narrow-band imaging (NBI) or blue laser imaging (BLI) observation followed by LCE observation in the esophagus using a high-definition endoscope at the endoscopic examination of lesion detection; and (4) biopsy-proven or strongly suspected squamous cell carcinoma. Patients with a history of chemotherapy, radiotherapy, or surgery for esophageal cancer were excluded. Lesions were classified into the IEE group (detected by NBI/BLI) and the LCE group (detected only after Lugol staining). The lesion in the IEE group were defined when the lesion was clearly visualized and in focus on the endoscopic images with NBI or BLI, or the endoscopic report described that it was detected with NBI/BLI. We evaluated the features of the lesions in the LCE group by comparing the clinicopathological characteristics between the lesions in the IEE group and LCE group. The endpoints were proportion of　LCE detected lesion and the proportion of target ESCC, defined as ESCC with pathological invasion depth of the muscularis mucosae (pT1a-MM) or deeper and/or positive lymphovascular invasion (LVI) on histological evaluation after ER.

Results

A total of 122 lesions in 96 patients were included. The IEE group comprised 99 lesions (81.1%) in 75 patients, while the LCE group comprised 23 lesions (18.9%) in 21 patients, thus proportion of LCE detected lesion was 18.9%. Most patients (92.7%, 89/96) had grade C of Lugol voiding staining. The median lesion size was 15 mm (range: 4-60 in the IEE group, which was higher than that in the LCE group at 10 mm (5-30). The lesions located on the anterior (23.5%) and left wall (31.3%) tended to be more frequently detected by LCE than those on the right (10.8%) and posterior wall (13.9%). Finally, 26 lesions were treated with EMR and 96 with ESD. The pathological diagnosis was pT1a-MM in 5 lesions and pT1b-SM1 in 2, resulting in the proportion of target ESCC of 5.7% (7/122). By group, the proportions of target ESCC were 7.1% (7/99) in the IEE group and 0% in the LCE group.

Conclusion

The characteristics of missed lesions in IEE observation tended to be small and located on the left or anterior wall of esophagus at surveillance endoscopy. Furthermore, all of these lesions were curatively resected with ER, resulting pT1a-EP/LPM without LVI in the pathological diagnosis.

Introduction

Gastric endoscopic submucosal dissection (ESD) has become increasingly popular worldwide as a less invasive curative treatment for early gastric cancer. However, ESD requires highly endoscopic technical skills, and it is important for trainees to develop effective training methods for ESD. ESD training is generally conducted using extracted porcine digestive tracts, but there are several issues regarding ethics, costs, infection, and logistics. In collaboration with KOTOBUKI Medical, we have developed the G-Master, a training model that can simulate ESD in several locations in the stomach. Since G-Master uses plant-derived mucous membrane sheet, there is no contamination and training can be easily performed using endoscope units and devices that are commonly used in clinical practice. Although the G-Master has enabled pre-training before actual ESD at facilities that have adopted it, it is unclear whether it contributes to the improvement of endoscopic technical skills of trainees. In this study, we clarified the usefulness of the G-Master training for inexperienced ESD trainees.

Aims & Methods

The ESD data were collected for the first through fifth gastric ESD cases performed from March 2018 through February 2022 by 15 ESD-inexperienced endoscopists at five participating centers. The ESD data were divided into two groups, one with G-Master training and one without G-Master training and the endpoints were compared retrospectively. The endpoints were procedure speed, perforation rate, operator changing rate, and en bloc resection rate, endoscopists experiences, and clinicopathological features. The resection speed was calculated as the resected area of the specimen divided by the procedure time (mm2/min). The group with G-Master training was defined as the group of trainees who always had at least one ESD training session with G-Master before each ESD. The group without G-Master training was defined as the group of trainees who had never done G-Master ESD training.

Results

A total of 75 gastric ESD cases were enrolled, with 25 cases in the group with G-Master training performed by 5 ESD-inexperienced endoscopists and 50 cases in the group without G-Master training performed by 10 ESD-inexperienced endoscopists. There was no difference between the two groups in endoscopists experiences including the years after graduation from medical school, the number of esophagogastroduodenoscopies and colonoscopies performed, and clinical features of gastric ESD cases including the location or size. In the group with G-Master training, the median procedure speed for all cases was significantly faster (with vs without G-Master: 13.1 mm2/min vs. 8.1 mm2/min, p>0.001). And the procedure speed of the training group was linearly improved from the initial to the last cases (with vs without G-Master: initial case; 11.8 mm2/min vs 8.5 mm2/min, last case; 23.1 mm2/min vs 12.0 mm2/min). Additionally, the rates of perforation (0 case (0%) vs 1 case (2%)) and operator change to expert (5 cases (20%) vs 15 cases (30%)) were lower. There was no difference in en bloc resection rate between the two groups.

Conclusion

It was suggested that performing G-Master training before actual ESD could improve the endoscopic technical skills of trainees who are inexperienced in ESD.

Introduction

Photodynamic therapy (PDT) is one of the local salvage treatment options for local failure after chemoradiotherapy (CRT) or radiotherapy (RT) for esophageal squamous cell carcinoma (ESCC). PDT using talaporfin sodium, second-generation photosensitizer, has shown acceptably high local complete response (L-CR) rate for local failure after CRT or RT. PDT is usually performed via ordinary sized conventional endoscopes (CE), however, some patients with local failure that indicated for PDT have the esophageal stenosis due to CRT/RT or endoscopic resection. The ultra-thin endoscope (UTE) is sometimes used for such case unavoidably, but it might be difficult to illuminate stably due to less operability of UTE. Therefore, there are concern about decrease in the efficacy of PDT and increase in adverse events due to the inappropriate illumination for the lesion.

Aims & Methods

This study aimed to clarify the efficacy and safety of PDT using UTE (UTE-PDT) compared with PDT using CE (CE-PDT). This retrospective study enrolled the consecutive patients underwent PDT with talaporfin sodium using CE or UTE for histologically proven local failure of ESCC between October 2015 and June 2022 at the National Cancer Center Hospital East. The inclusion criteria of PDT in this study were as follow;
1) invasion depth limited within T2,
2) located at thoracic esophagus,
3) <5 cm in tumor size,
4) <3/4 of the esophageal circumference,
5) absence of lymph node or distant metastasis, and
6) patient’s refusal or unsuitable physical condition for salvage surgery.
We evaluated the L-CR rate and the incidence of adverse events in the UTE-PDT and the CE group. The L-CR was defined when absence of an obvious residual tumor, disappearance of post-PDT ulcer and scarring, and histological confirmation of absence of cancer cells by biopsy. We used L590ZW (Fujifilm Co., Tokyo, Japan) or GIF-H190 (Olympus Co., Tokyo, Japan) as CE, and used L580NW (Fujifilm Co., Tokyo, Japan) as UTE for PDT.

Results

Eight patients in the UTE-PDT group and 87 patients in the CE-PDT group were enrolled in this study. The tumor size (median, [range]) before PDT was 20mm [4-40mm] in the UTE group and 20mm [10-20mm] in the CE group, and the circumference of the lesion (1/2< /≤1/2) was 7/1 patients in the UTE group and 84/3 patients in the CE-PDT group. The number of the patients with recurrent/residual tumor/unknown in the appearance of local failure before PDT were 6/2/0 patients in the UTE-PDT group and 47/34/6 patients in the CE-PDT group, and those with T1/T2 in invasion depth before PDT were 7/1 patients in the UTE-PDT group and 74/13 patients in the CE-PDT group. In the UTE-PDT group, endoscopic resection was the most common cause of the esophageal stenosis (50.0%). Finally, the L-CR rate was 50.0% (4/8) in the UTE-PDT and 59.3% (48/81) in the CE-PDT group, excluding 6 cases with insufficient follow-up. As for adverse events in the UTE-PDT/CE-PDT group, esophageal pain in 12.5%/41.4%, skin phototoxicity in 0.0%/5.7%, and esophageal stricture with grade 2 after PDT in 12.5%/4.6% were observed, but all were grade 2 or less.

Conclusion

Comparing with PDT using CE, PDT using UTE for local failure after CRT/RT for ESCC are favorable and can be the promising therapeutic option for the patients without other treatment option. To improve the efficacy and reduce the esophageal stricture of UTE-PDT, several devices designed specifically for UTE should be further developed.

Introduction

It is well known that head and neck squamous cell carcinoma (HNSCC) often occur in patients with esophageal squamous cel carcinoma (ESCC) synchronously or metachronously. As a result of improvements in endoscopic system and observation techniques, the number of patients with advanced ESCC who are detected superficial HNSCC before treatment is increasing. However, subsequence clinical course of superficial HNSCC in patients who were treated with systemic neoadjuvant triplet chemotherapy for advanced ESCC has been unknown.

Aims & Methods

The aim of this study is to clarify the influence of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy for superficial HNSCCs and clinical course of these lesions. The patients with advanced ESCC and superficial HNSCC, which were diagnosed by biopsy, who were treated with neoadjuvant DCF therapy for esophagectomy at our institution between January 2015 and December 2022 were retrospectively included. We excluded the patients who had a history of surgery or radiotherapy for HNSCC, chemotherapy within 5 years for any malignancy, or no endoscopic observation after the start of DCF therapy. At our institution, the endoscopic assessments were routinely performed for ESCC and HNSCC after the completion of each course of DCF therapy and reported the morphological changes in HNSCC lesions. In this study, endoscopic complete response (eCR) was defined as the disappearance of visible tumors in endoscopic observation and did not require histological confirmation by biopsy. The proportion of eCR in HNSCCs after DCF therapy, and 2-year cumulative recurrence rate of HNSCCs after eCR for the patients who did not receive chemotherapy or radiotherapy after surgery were evaluated. In addition, the difference in clinicopathological features between the patients with or without achievement of eCR were evaluated.

Results

Finally, 45 patients (56 lesions) were analyzed. Thirty-nine lesions (69.6%) were in the hypopharynx, 7 (12.5%) in the larynx, and 10 (17.9%) in the oropharynx. The median lesion size was 20 mm (range: 3-40 mm). Of all lesions, 45 lesions (80.4%) achieved eCR by DCF administration. There were no significant differences in tumor location, lesion size, and the number of administrated DCF course between the patients with or without achievement of eCR. On the histological evaluation using the biopsy samples, the lesions without subepithelial invasion were more likely to achieve eCR than those with invasion [88.9% vs 63.2%, P=0.035]. Seven patients who received additional chemotherapy or radiotherapy after esophagectomy and two who did not receive endoscopic assessment after esophagectomy were excluded for long-term analysis. Then, of the 39 lesions in 32 patients with achievement of eCR, 15 lesions (51.7%) had a local recurrence during the median follow-up period of 11 months (range 1.9-87 months), and the 2-year cumulative recurrence rate was 57.6%. Of these local recurrences, 12 lesions were performed with endoscopic laryngopharyngeal surgery, two with radiotherapy, and the other was not treated because of progression of ESCC.

Conclusion

Superficial HNSCCs mostly achieved eCR after neoadjuvant DCF therapy for locally advanced ESCC, however, more than half of them had a local recurrence thereafter. Therefore, the appropriate endoscopic follow-up after esophagectomy, early detection of local HNSCC recurrence, and therapeutic intervention were necessary.

Introduction

Chemoradiotherapy (CRT) is a standard non-surgical treatment for esophageal squamous cell carcinoma (ESCC). One of the major disadvantages of CRT is poor local control, and salvage esophagectomy is generally indicated for local failure; however, it is invasive with a high rate of postoperative complications and mortality so that patients often refused or are intolerant to salvage esophagectomy. Alternatively, photodynamic therapy (PDT) with talaporfin sodium (TS) is less invasive salvage treatment for local failure after CRT/ radiotherapy (RT) and was reported to have relatively high local complete response (L-CR) rate and few adverse events (AEs) in the short term. However, long-term outcomes of PDT with TS are unknown.

Aims & Methods

This retrospective study aimed to clarify the long-term outcomes of PDT with TS for local failure after CRT/RT for ESCC. Patients who underwent PDT with TS for histologically proven local failure of ESCC between December 2012 and December 2021 at the National Cancer Center Hospital East were enrolled. Patients with other active cancers or a prior history of PDT were excluded. Basic indication criteria of PDT were as follows: invasion depth limited to the shallow muscle layer, <1/2 of the esophageal circumference, absence of metastasis, and patient’s refusal or unsuitable physical condition for salvage surgery. We assessed L-CR rate, incidence of AEs, clinical courses after PDT, 3-year overall survival (OS), progression free survival (PFS) and major PFS (mPFS) in which major disease progression after PDT which defined as disease progression requiring more invasive treatment than repeated endoscopic treatment and death from all causes were considered as events. We also assessed pre-PDT factors associated with L-CR. L-CR was defined as no apparent residual tumor, disappearance of post-PDT ulcer and confirmation of the scar formation, and absence of cancer cells in biopsy.

Results

108 patients (92 men; median age 74 years [range, 52-88 years]) were enrolled. Patients with pre-CRT/RT cT1/ T2/ T3/ T4/ unknown were 50/ 22/ 24/ 9/ 3. Those with residual lesion/ local recurrence/ unknown were 63/ 39/ 6. Patients with pre-PDT ycT1a/ T1b/ T2 were 6/ 85/ 17. Pre-PDT median lesion size was 20 mm (range, 4-50 mm). 60 patients achieved L-CR after PDT, 41 had L-nonCR, and 7 were not evaluable. L-CR rate of PDT was 58.8% (60/101). During median follow-up of 23 months (range, 1-90 months), 39 patients (36.1%) finally had no recurrence after PDT. 18 patients, including 8 with L-nonCR after PDT and 10 with local recurrence after achieving L-CR, underwent re-endoscopic treatments alone and remained disease-free afterward. The other 44 patients had major disease progression, and 15 received salvage surgery among them. As for the lesion characteristics associated with L-CR, the lesions with <1/2 circumference and with <20 mm in size were more likely to achieve L-CR than those with ≥1/2 circumference (64.4% vs. 16.7%, P=0.003) and with ≥20 mm (80.0% vs. 45.2%, P=0.001), respectively. The 3-year OS/ PFS/ mPFS of all patients were 78.1%/ 29.8%/ 48.1%. The 3-year OS of L-CR cases was better than that of L-nonCR cases (89.3% vs. 67.7%, P=0.003). There was no grade 3 < AEs. Non-cardiac chest pain (60.2%), skin phototoxicity (4.6%), and esophageal stricture requiring balloon dilatation (4.7%) occurred.

Conclusion

PDT with TS for local failure after CRT/RT for ESCC showed the preferable long-term outcomes. Moreover, achieving local control with PDT could improve prognosis of patients even with local failure after CRT/RT.

Introduction

Patients with multiple Lugol-voiding lesions (mLVLs) in esophageal squamous cell carcinoma (ESCC) were known to have an increased risk of metachronous ESCC or pharyngeal and laryngeal squamous cell carcinoma (PLSCC) following endoscopic resection (ER), necessitating intensive endoscopic surveillance. The Japan Esophageal Cohort study, a multicenter prospective study evaluating the cumulative incidence of metachronous ESCC after esophageal ER, demonstrated that ER was selected as the initial treatment for most newly detected metachronous ESCC (72/74 patients). However, in clinical practice, ESCC or PLSCC outside the indications for ER are occasionally detected. Additionally, patients with mLVLs are known to have a high risk of developing other secondary primary cancers, nonetheless, the long-term clinical course in this population remains unclear.

Aims & Methods

The aim of this retrospective study was to evaluate the long-term prognosis of patients with mLVLs after endoscopic submucosal dissection (ESD) for superficial ESCC. This study included patients with mLVLs who underwent ESD for primary ESCC at our institution between April 2008 and August 2016. The exclusion criteria were patients with non-curative resection after ESD requiring additional treatment, such as submucosal invasion, positive vertical margins (pVM1), or lymphovascular invasion (LVI), and patients with a follow-up period of less than one year. After esophageal ESD, endoscopic surveillance was conducted every six months to one year, and metachronous cancers were considered for treated if detected. The cumulative incidence of metachronous ESCC and PLSCC, as well as the cumulative incidence of metachronous major ESCC and PLSCC, and overall survival (OS) were evaluated. Major ESCC were defined as lesions outside the indications for ER or those in which ER was performed resulting in a non-curative resection. Major PLSCC were defined as lesions outside the indications for ER or endoscopic laryngopharyngeal surgery (ELPS), or those in which ER or ELPS were performed resulting in pVM1 or LVI.

Results

A total of 140 patients were included, with a median age of 69 years (range: 47-86), and 30 patients (21.4%) had a history of head and neck cancer. During the median follow-up of 8.8 years (range: 1.2–15.5), 85 patients (60.7%) developed metachronous ESCC, all of whom were initially treated with ER, and 81 (95.3%) managed with ER alone, including repeated ER. Meanwhile, 35 patients developed metachronous PLSCC, 30 (85.7%) of whom were managed with ELPS alone. The cumulative incidence of metachronous ESCC and PLSCC at 5/10 years was 47.5%/67.1% for ESCC, and 13.8%/35.4% for PLSCC, respectively. The cumulative incidence of metachronous major ESCC and PLSCC at 5/10 years was 0.8%/2.8% for ESCC, and 1.5%/1.5% for PLSCC. Additionally, 30 (21.4%) patients died during follow-up, including progression of superficial metachronous ESCC (n=1) and superficial metachronous PLSCC (n=2) under observation after detection due to poor performance status, recurrences of previously treated PLSCC (n=7), aspiration pneumonia (n=4), hematological malignancies (n=3), tongue cancer (n=2), and others (n=11). The 5- and 10-year OS rates were 92.4%/ 79.5%.

Conclusion

In patients with mLVLs, endoscopic surveillance including pharyngo-laryngeal area following ESD for ESCC enabled early detection of metachronous lesions, the majority of which were successfully treated with ER. However, deaths from other causes were not negligible, highlighting the importance of careful long-term systemic monitoring.