Similar survival after endoscopic submucosal dissection and esophagectomy in early esophageal cancer and synchronous or metachronous head and neck cancer

Patients with esophageal cancer who underwent ESD or esophagectomy between November 2002 and December 2019 at the Kaohsiung Branch of Chang Gung Memorial Hospital were reviewed retrospectively. We evaluated patients’ pathological reports that showed the presence of stage 0 or I disease. All patients were assessed by a multidisciplinary team including surgeons, oncologists, radiation oncologists, radiologists, and gastroenterologists. Pretreatment evaluation included esophagogastroduodenoscopy (EGD), chest computed tomography with contrast enhancement, endoscopic ultrasonography, and positron emission tomography. The disease stage was confirmed using the 8th American Joint Committee on Cancer (AJCC) staging system. All patients will be listed in multiple multidisciplinary team meetings for treatment options. If the clinical survey shows that the lesion fits the criteria for endoscopic submucosal dissection [11], gastrointestinal physicians will discuss endoscopic submucosal dissection with the patients. If patients refuse or do not fit the criteria of endoscopic submucosal dissection, they will go on esophagectomy (since all of them are clinically operable by retrospective database selection). We excluded patients who underwent intervention at another hospital, were treated with radiofrequency ablation, had received adjuvant therapy such as concurrent chemoradiotherapy or chemotherapy alone before the intervention, and/or had unavailable medical records. Some patients were lost to follow-up for a long period. This study was approved by the Institutional Review Board of the Kaohsiung Chang Gung Memorial Hospital. The IRB certificate number is “202300639B0.”

Three different surgeons performed esophagectomies in these patients, and two experienced gastrointestinal endoscopists performed esophageal ESD. All patients underwent esophagectomy using the McKeown or Ivor-Lewis procedure. We used the same operating room settings, team members, and surgical devices for all patients. The esophagectomy specimens were sent to the pathology lab for reports including whole resected esophagus, thoracic and abdominal lymph nodes. Pathologists evaluated tumor and depth, lymphvascular invasion, resection margin and classified the stage in line with the American Joint Committee on Cancer eighth edition. About endoscopic submucosal dissection, the used equipment included flexible endoscopes (GIF-Q260J, Olympus, Tokyo, Japan) with a distal attachment (Olympus, Tokyo, Japan) and the Hybrid Knife™ water-jet system (ERBE, Tubingen, Germany) or Dual Knife-J™ electrosurgical knife (Olympus, Tokyo, Japan). The submucosal injection used during ESD included normal saline with bosmin and indigo-carmine with Hybrid knife™ and glycerol with bosmin and indigo-carmine with Dual Knife-J™ [12]. We performed a circumferential incision in the esophageal mucosa after marking the tumor margin with an electrosurgical knife, rather than dissecting the submucosa. In some cases with large tumors or severe submucosal fibrosis, we used the traction method with an endoscopic clip and dental trephine to complete the submucosal dissection. Hybrid-ESD delimited as resection was completed using Captivator II™ Single Use Snare (Boston Scientific, Natick, MA, USA) [12] after circumferential incision and adequate partial submucosal dissection. An electrosurgical knife or the Coagrasper™ Hemostatic Forceps (Olympus, Tokyo, Japan) was used for hemostasis during and after complete ESD to prevent post-ESD bleeding [12]. Sucralfate gel was sprayed directly on the post-ESD wound to assess the presence of a possible minor bleeder. After ESD, the specimens were oriented by fixing the periphery with thin needles on a plate immediately before immersion in formalin. Post-ESD specimens were sent for pathological examination and serially sectioned at 2 mm intervals. Both the lateral and vertical margins were assessed microscopically, and the depth of tumor invasion was evaluated based on the degree of differentiation and lymphovascular infiltration. R0 resection was defined as en bloc resection with all histologically negative margins.

We used two scales to compare the results of ESD and esophagectomy. Overall survival was defined as the period from the first intervention date of esophagectomy or ESD to the last contact date. If a patient died (regardless of the cause of death), we delimited it as an event. If a patient survived, it was delimited and censored. Relapse-free survival was defined as the period from the first intervention date of esophagectomy or ESD to the last contact date. If a patient died or had a computer tomography scan or EGD showing progression in the regional lymph node or residual esophagus, we delimited it as an event. If an image was stable, it was delimited and censored.

Synchronous tumors were confirmed within 6 months of the identification of the index tumor, and metachronous tumors were confirmed more than 6 months after the index tumor [13].

Data were analyzed using MedCalc® Statistical Software version 20 (MedCalc Software Ltd, Ostend, Belgium; https://​www.​medcalc.​org; 2021). A χ2 test was used to contrast data between the two groups. The Kaplan–Meier method was used for univariate survival analysis, and the difference between survival rates was analyzed using a log-rank test. Factors were entered into a Cox regression model in a forward manner to analyze their relative prognostic importance. For all analyses, two-sided tests of significance were used, with p < 0.05 indicating statistical significance.