Introduction

The therapeutic effect of recurrent laryngeal nerve (RLN) dissection in the treatment of esophageal cancer, particularly squamous cell carcinoma, is well-established. However, due to the risk of RLN palsy as a consequence, this procedure is often avoided. Nonetheless, the prevalence of this adverse event and its impact on prognosis remain unclear.

Aims & Methods

In this study, we aimed to evaluate the influence of recurrent laryngeal nerve palsy and long-term effects on prognosis. Moreover, we introduce some basic science of treating injured nerve using amnion membrane sheet.
We analyzed 726 cases of esophageal cancer who underwent bilateral recurrent laryngeal nerve lymphadenectomy during esophagectomy between 2000 and 2021. Cases with combined nerve resection and R2 resection were excluded. Recurrent laryngeal nerve palsy was confirmed by bronchoscopy on the first postoperative day, if even a slight difference in the movement of the vocal cords between the left and right sides was detected.

Results

RLN palsy was observed in 40.7% of cases (left: 234 cases, right: 31 cases, bilateral: 30 cases), with 12 cases experiencing paralysis lasting over a year. Analysis revealed significantly higher rates of complications such as aspiration (p < 0.0001), postoperative pneumonia (p = 0.0004), and prolonged hospital stay (p < 0.0001) in RLN palsy cases. Furthermore, there were associations between postoperative pneumonia and patient factors including age (p = 0.0364), sex (p = 0.0066), RLN palsy (p = 0.0005), and reconstruction route (p = 0.0098), each identified as independent risk factors in multivariate analysis. However, only age and sex showed associations with pneumonia-related mortality. Long-term prognosis analysis using propensity score matching revealed slightly poorer outcomes in the RLN palsy group, although no statistically significant difference was observed.

Additionally, we are conducting research on a treatment method using amniotic membrane sheets in a sciatic nerve injured rat model. Electromyography studies showed a trend toward improved motor function in the amniotic membrane sheet treatment group compared to the control group at 8 weeks post-injury (p = 0.0887). Further investigation with increased sample size is planned to refine this approach for future clinical application.

Conclusion

Although RLN palsy after esophageal cancer surgery did not affect patient prognosis in the long term, we discovered it as a cause of aspiration and postoperative pneumonia in the short term. With the growing understanding of respiratory complications as important prognostic factors in various cancers, including esophageal cancer, strategies to prevent RLN palsy are crucial. Amniotic membrane sheets represent a potential intervention for the early recovery of RLN palsy.

Introduction

In the treatment of esophageal carcinoma, abdomino-thoracic esophagectomy is the curative therapeutic option, often combined with perioperative (radio-)chemotherapy. This procedure is associated with high complication rates and significant mortality. Anastomotic leakage, with a pooled incidence of 11% (ranging from 0% to 49%)¹, constitutes a major postoperative complication. New therapeutic options, such as the EndoVac (Stent) system, offer promising approaches for its management. The aim of this study was to identify risk factors for the occurrence of anastomotic leaks and to evaluate the effectiveness of various treatment methods.

Aims & Methods

We present data from 2022–2024 collected at the University Medical Center Göttingen, a high-volume center for esophageal surgery. A total of 242 patients who underwent abdomino-thoracic esophagectomy, either as primary treatment or after neoadjuvant therapy, were included. Structured data collection and analysis were carried out using Excel and GraphPad Prism.

Results

In this patient cohort, 79.3% were male (n=192) and 20.7% female (n=50), with a mean age of 65.4 years and a mean BMI of 26.1 kg/m² at the time of surgery. The most common pre-existing conditions were 56.6% arterial hypertension (n=137), 7,9% COPD (n=19), 21% diabetes mellitus (n=51), as well as coronary artery disease (CAD) and peripheral arterial disease (PAD), each 8.2% (n=20). Histologically, 80.1% (n=194) adenocarcinomas and 19.4% (n=47) squamous cell carcinomas. 88.8% of patients received neoadjuvant therapy (n=215): 35.5% radiochemotherapy (n=86) and 53% chemotherapy (n=129). Of all patients, 24.8% (n=60) underwent primary open surgery and 75,3% (n=182) had minimally invasive hybrid procedures. By 2024, minimally invasive approaches had increased to 83.3% (n=86).
Anastomotic leakage occurred in 25 patients (10.3%), with clinical manifestation appearing on average 8 days postoperatively (range: 1–29 days). An association with the occurrence of anastomotic leakage was observed for nicotine abuse (OR 1.35; 95% CI: 0.60–3.11), alcohol consumption (OR 1.69; 95% CI: 0.66–4.24), coronary artery disease (CAD), and peripheral arterial disease (PAD) (each OR 2.37; 95% CI: 0.80–7.81); however, none reached statistical significance in Fisher’s exact test (all p > 0.05). Complete remission (24.4%, n=59) was significantly associated with an increased risk of leakage (OR 3.51; 95% CI: 1.53–7.86; p = 0.005).
All 25 anastomotic leaks were initially treated with EndoVac, healing successfully in 21 cases (96%). Four patients (16%) required revision surgery. An EndoVacStent was implanted in 52% of cases (n=13), with 20% receiving only an EndoVacStent (n=5) and 32% treated with a combination of sponge and stent (n=8). The average duration of EndoVac therapy was 15 days (range: 1–42 days), with the system being exchanged three times on average. In-hospital mortality was 1.6% (n=4).

Conclusion

In summary, the EndoVac and EndoVacStent systems have proven to be safe and effective treatment options for anastomotic leakage. Patients with complete remission showed an increased susceptibility to anastomotic leakage. Our data supports the importance of studies like ESORES (DRKS00022050)² and PRESTO (NCT05713838)³, investigating non-operative treatment approaches for clinical complete remission cases followed by a watch-and-wait strategy.

References

1. Sivesh K Kamarajah, Aaron Lin, Thahesh Tharmaraja, Yashvi Bharwada, James R Bundred, Dmitri Nepogodiev, Richard P T Evans, Pritam Singh, Ewen A Griffiths, Risk factors and outcomes associated with anastomotic leaks following esophagectomy: a systematic review and meta-analysis, Diseases of the Esophagus, Volume 33, Issue 3, March 2020, doz089, https://doi.org/10.1093/dote/doz089
2. ESORES – A prospective registry study for patients with esophageal cancer and clinical complete response after neoadjuvant therapy. German Clinical Trials Register (DRKS00022050). https://www.drks.de/DRKS00022050
3. PRESTO – Prospective evaluation of watch-and-wait strategies in complete responders to neoadjuvant therapy for esophageal cancer. ClinicalTrials.gov (NCT05713838).
https://clinicaltrials.gov/ct2/show/NCT05713838

Introduction

Esophageal squamous cell carcinoma (ESCC) is a major global health concern, with a high recurrence rate after chemoradiotherapy (CRT). Despite being a curative approach, CRT alone is often insufficient, leading to local recurrence in 30–40% of cases (1). Salvage treatments such as surgery and endoscopic resection have limitations, particularly in patients with comorbidities or advanced lesions (2). Photodynamic therapy (PDT) using talaporfin sodium (TS) has emerged as a promising, minimally invasive salvage treatment, offering advantages such as reduced phototoxicity and repeatability (3). Since its approval in Japan in 2015, TS-PDT has gained traction, yet further clinical evidence is needed to validate its efficacy and safety. This study aims to evaluate the clinical outcomes of TS-PDT as a salvage treatment for locally recurrent or residual ESCC following CRT or radiotherapy (RT).

Aims & Methods

A retrospective study was conducted at Nagoya City University Hospital between May 2016 and December 2023. A total of 29 patients with histologically confirmed local recurrence or residual ESCC post-CRT/RT were included. Eligible patients had lesions classified as ≤T2, without lymph node or distant metastasis. TS-PDT was administered with a diode laser (664 nm) 4–6 hours post-intravenous TS injection (40 mg/m²). Patients were monitored for adverse events, local complete response (L-CR), progression-free survival (PFS), and overall survival (OS). Kaplan–Meier analysis was used for survival estimation, and comparisons between single and multiple PDT sessions were evaluated.

Results

Table 1. The best response to PDT
	Local-CR	Non L-CR	L-CR rate
patients	22	5	81.5%
lesions	36	5	87.8%
T1b lesions	28	1	96.6%
T2 lesions	8	4	66.7%

Among the 29 patients (23 males, 6 females; median age, 72 years), TS-PDT achieved an L-CR rate of 82.1% per patient and 87.8% per lesion, with superior outcomes in T1b lesions (96.6%) compared to T2 lesions (66.7%) (Table1). The median local PFS was 1,324 days, and the median PFS was 912 days. OS was not reached during follow-up, with a 3-year survival rate of 70.7%. Seventeen patients underwent a single PDT session, while 12 required multiple sessions. The 3-year OS rate was 83.3% in the single-session group and 44.4% in the multiple-session group. No skin phototoxicity was observed. Adverse events included esophageal strictures (1 case, asymptomatic) and esophageal perforations (2 cases), one of which required surgical intervention.

Conclusion

TS-PDT demonstrated high local control rates and favorable survival outcomes, making it a promising salvage therapy for ESCC recurrence post-CRT/RT (4). Despite some adverse events, its minimal invasiveness and reduced phototoxicity enhance its applicability, particularly in elderly or high-risk patients. The effectiveness of multiple PDT sessions supports its role as a flexible treatment strategy. Further multicenter prospective trials are warranted to optimize patient selection, treatment protocols, and long-term outcomes, solidifying TS-PDT as a key salvage therapy for recurrent ESCC (5).

References

1. Hironaka S, Ohtsu A, Boku N, et al.: Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T(2-3)N(any) M(0) squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys 57: 425-433, 2003.
2. Tachimori Y, Kanamori N, Uemura N, Hokamura N, Igaki H and Kato H: Salvage esophagectomy after high-dose chemoradiotherapy for esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 137: 49-54, 2009.
3. Yano T, Kasai H, Horimatsu T, et al.: A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer. Oncotarget 8: 22135-22144, 2017.
4. Ikebuchi Y, Yoshida A, Kurumi H, et al.: Salvage Photodynamic Therapy Using Talaporfin Sodium for Local Failure of Esophageal Squamous Cell Carcinoma. Yonago Acta Med 64: 120-125, 2021.
5. Kai K, Nakashima K, Kawakami H, et al.: Clinical Impact of the Charlson Comorbidity Index on the Efficacy of Salvage Photodynamic Therapy Using Talaporfin Sodium for Esophageal Cancer. Intern Med 63: 903-910, 2024.

Introduction

Recent improvements in endoscopic diagnostic techniques have made it possible to detect early-stage superficial laryngopharyngeal cancer, and endoscopic resection has become one of the standard treatments in Japan1). However, it is not fully known to what extent endoscopic treatment alone is curative.

Aims & Methods

To clarify the relationship between depth and lymph node metastasis in superficial laryngopharyngeal cancer. From August 1996 to April 2023, we experienced 501 cases of 810 lesions of superficial laryngopharyngeal cancer. Of these, 396 cases with 652 lesions (462 in the hypopharynx, 149 in the oropharynx, and 41 in the larynx) that were resected orally without prior treatment and followed for more than 1 year were included to investigate the relationship between depth and late lymph node metastasis.

Results

Endoscopic classification of the treated lesions was 81 lesions of type 0-Ⅰ(protruded type), 164 lesions of type 0-IIa(elevated type), 391 lesions of type 0-IIb(flat type), and 16 lesions of type 0-IIc (depressed type). Type 0-IIb was the most frequent.
Histopathologically evaluated 174 cases of intraepithelial carcinoma with 249 lesions showed no metastasis. On the other hand, of the 403 lesions in 295 cases of subepithelial invasive cancer (T1, tumor size less than 2cm: 213 lesions, T2, tumor size 2-4cm or smaller: 159 lesions, T3, tumor size greater than 4cm: 31 lesions), 30 lesions in 28 cases(9.5%) had later lymph node metastasis. Two of 305 lesions (0.65%) with tumor thickness less than 1000 μm were positive for metastasis. By size, 1 of 178 lesions in T1(0.6%), 1 of 111 lesions(0.9%) in T2, and 0 of 16 lesions in T3 were positive for metastasis. On the other hand, 28 of 98 lesions (28.6%) with tumor thickness greater than 1000 μm were positive for metastasis. By size, 6 of 35 lesions in T1(17.1%), 17 of 48 lesions(35.4%) in T2, and 5 of 15 lesions(33.3%) in T3 were positive for metastasis. The frequency of lymph node metastasis by endoscopic type was 20 of 81 lesions(24.7%) for type 0-I, 8 of 164 lesions (4.9%) for type 0-IIa, 1 of 391 lesions(0.25%) for type 0-IIb, and 1 of 16 lesions (6.25%) for type 0-IIc, metastasis was seen more frequently in type 0-I. The observation of brownish areas and brown dots with Image Enhanced Endoscopy is useful for detecting early-stage cancer. When examining the depth of the disease, the Valsalva method is recommended to focus on type 0-I lesions with a thickness of 1 mm or more and a well-stretched pharyngeal mucosa.

Conclusion

Superficial carcinomas with a thickness greater than 1 mm should be noted for late lymph node metastasis.

References

1) Watanabe A, Taniguchi M, Kimura Y, et al. Synopsis of transoral endoscopic laryngopharyngeal surgery for superficial pharyngeal cancers. Head Neck 2017; 39: 1779-1787

Disclosure

The authors have no financial conflicts of interest disclose concerning the study.

Introduction

Stretta, a minimally invasive endoscopic procedure, has demonstrated efficacy in improving GERD symptoms by delivering radiofrequency energy to the lower esophageal sphincter. Despite its effectiveness, there is limited understanding of Stretta's impact on the epithelial barrier function.

Aims & Methods

This study aims to investigate changes in epithelial barrier function in GERD patients who underwent Stretta treatment. Tight junction gene expression levels, measurement of dilated intercellular spaces (DIS), and electrophysiological and permeability properties of the esophageal epithelium were investigated in order to determine the epithelial barrier function characteristics of patients treated with Stretta.
Six Stretta-treated (3 men, 38.5±4.9 years) patients and 15 (7 men, 36.2±6.3 years) healthy volunteers (HV) were included in the study. Esophageal epithelial biopsies taken during endoscopy were used as study material. In order to determine tight junction gene expressions, qRT-PCR method was used for the expression levels of 6 (E- cadherin, Zonula ocludens 1, Zonula ocludens 2, Claudin 1, Claudin 4, Occludin) genes. Ussing chamber system was used to determine the transepithelial resistance (TEER) of the esophageal epithelium and permeability properties were examined by a fluorometric method. In DIS measurements, For each patient, photographs were taken from 10 different areas without artifacts under the light microscope at 1000x magnification. Ten vertical measurements were made continuously around the single epithelial cell with the largest DIS between the upper part of the Stratum Basale and the six parts of the Stratum Spinosum. A total of 100 blind measurements were made by a single investigator for each patient.

Results

In comparing the gene expressions of tight junctions before (Pre-str) and after Stretta (Post-str), it was observed that only the expression of the Claudin 4 gene was 6.91 (p=0.02) fold higher in the Post-str group compared to the Pre-str group. Similarly compared to the HV group, the Post-str group exhibited a 6.02-fold (p=0.001) increase in Claudin 4 expression.
Comparing the TEER results between the pre-str (110.8 Ω) and post-str (151.7 Ω) groups, although there is a numerical increase, no statistically significant difference was observed. In addition, the TEER values of the HV (165,8 Ω ) group were statistically significantly higher than the Pre-str group. Upon examining the permeability results, it was determined that the Post-str (30.1 pmol) group had lower permeability compared to the Pre-str (67.3 pmol) group (p=0.043), while there was no statistically difference observed between the HV (34.4 pmol) group and the Stretta groups.
According to the study findings, the group that exhibited the largest DIS was the Post-str (0.974±0.212) group. However, no statistically significant difference was observed between the Pre-str (1.030±0.266) and Post-str groups in terms of DIS. Notably, a significant difference (p=0.03) was only observed between the HV (1.374±0.269) group and the Post-str group.

Conclusion

In summary, our findings suggest that treatment with Stretta strengthens the epithelial barrier function, as evidenced by the increase in Claudin 4 expression and the corresponding decrease in fluorescent permeability. However, the lack of support from our DIS results in terms of gene expression and electrophysiological changes suggests the need for further investigation to fully understand the effects of Stretta treatment on the epithelial barrier.

Clinical Case Summary

39-year-old male, diagnosed with a gastroesophageal junction adenocarcinoma underwent a hybrid thoraco-laparoscopic oesophagectomy in October 2021.
On post-op day 13 patient developed fever not responding to antibiotics. Contrast enhanced computed tomography (CECT) of chest & abdomen with contrast swallow, identified an anastomotic leakage with a right side chest collection. Over-the-scope clip and oesophageal fully covered metal stent was used to attempt closure without success.
An 11mm atrial septal defect (ASD) closure device, which is a self-expanding, double umbrella shaped device made of nitinol wire mesh, was used to close the 5mm defect seen at the anastomotic site. Feeding was continued via nasojejunal tube.
CECT done 2 weeks and 6 months after insertion showed no contrast leak or evidence of recurrence. Oesophagogastroduodenoscopy done at 6 months showed the ASD closure device to have dislodged from the site and remain free in the stomach. The site of leak had completely closed. Patient remained asymptomatic, without any evidence of recurrence on CECT done 3 years after surgery.
This clinical case describes the novel, off label use of an ASD closure device to treat post-oesophagectomy anastomotic leakage , where other conventional endoscopic treatment methods have failed. Reports on similar application of this device in endoscopic treatment of anastomotic leakage are scarce worldwide (1-3), and long term patient outcomes upto 3 years have not been reported.
This method is more costly than alternate endoscopic treatment methods for anastomotic leakage. However, the unique structure of the ASD closure device which promotes tissue growth, and the availability of multiple disk and waist size variations contributes to a higher success rate than other conventional endoscopic treatment methods. Therefore the use of ASD closure devices can be considered where other alternatives have failed, when a minimally invasive treatment option is sought.

References

1. Repici A, Presbitero P, Carlino A, Strangio G, Rando G, Pagano N, et al. First human case of esophagus-tracheal fistula closure by using a cardiac septal occluder (with video). Gastrointest Endosc. 2010 Apr;71(4):867–9.
2. Subtil JC, Valenti V, Cienfuegos JA, Calabuig J, Hernández-Lizoain JL, Muñoz-Navas M. Successful endoscopic closure of multiple tracheoesophageal fistulas following implantation of two atrial septal defect occluders. Endoscopy. 2016;48:E346–7.
3. Coppola F, Boccuzzi G, Rossi G, Gaia S, Cosimato M, Recchia S. Cardiac septal umbrella for closure of a tracheoesophageal fistula. Endoscopy. 2010;42(SUPPL. 2).

Introduction

The safety of endoscopic submucosal dissection (ESD) in the context of resecting superficial tumors on Barrett's esophagus (BE) has been well assessed. However, there is limited knowledge regarding the oncological follow-up of BE and Barrett's esophagus after a combination of endoscopic resection and radiofrequency ablation.

Aims & Methods

A prospective, multicentric study involving 141 patients, enrolled between December 2016 and January 2019, and followed for three years. These patients underwent ESD for suspicious neoplasia lesions on BE, either alone or in combination with BE ablation. The primary outcome measure was the R0 resection rate for adenocarcinoma and high-grade dysplasia (HGD). Secondary outcome measures included rates of en bloc resection rate, R0 resection rate for adenocarcinoma or low-grade dysplasia, adverse event rate, overall and recurrence free survival at one and at three years, and the rate of complete remission of intestinal metaplasia at one year and three years.

Results

The R0 resection rate for carcinoma and HGD was 84,6% (110/130). R0 resection rate for invasive carcinoma was 80,8% (80/99). Seven early complications (< 48 hours) were observed, including 5 cases of bleeding and 2 cases of aspiration pneumonitis. No perforations occurred. Seventeen cases of esophageal strictures were reported. Recurrence was observed in 10 patients at 3 months, including 5 at the resection site, 5 at 12 months, and 3 at 36 months, totaling 18 recurrences over 3 years. 14 patients died during the follow-up, with 3 deaths attributed to esophageal carcinoma. The Complete Response to Intervention Monitoring (CRIM) was 63.7% in patients treated for Barrett's esophagus.

Conclusion

Endoscopic submucosal dissection is a safe and effective technique for treating early neoplastic lesions on BE, especially when combined with residual BE ablation. This study, one of the largest prospective studies on the subject, not only confirms the safety and efficacy of ESD but also provides valuable insights into post-resection tumor follow-up.