Squamous cell carcinomas (SCCs) and adenocarcinomas are two types of esophageal cancer. In Japan and the East, many SCCs are reported in the upper and middle thoracic esophagus, while in the West, there are many adenocarcinomas reported in the lower thoracic esophagus, up to the esophagogastric junction (EGJ) . BE is risk factor for esophageal adenocarcinoma and this histological type of lower thoracic esophagus and EGJ has increased worldwide [6, 7]. However, adenocarcinoma of the cervical and upper thoracic esophagus is very rare. Moreover, it is often found in advanced cancer, and its prognosis is poor . Previously, we reported a patient with adenocarcinoma in the upper thoracic esophagus who underwent surgery . In our department, among all patients who underwent esophageal cancer surgery in the last 10 years, two patients (0.6%) including this case had adenocarcinoma of the cervical to upper thoracic esophagus, which is also rare.
Since cervical or upper thoracic esophageal adenocarcinoma is rare, it is important to diagnose primary esophageal adenocarcinoma. In Japan, there is a definition of primary esophageal adenocarcinoma by Komei Nakayama, (a) tumors derived from the esophageal mucosa or mucous glands, (b) a healthy squamous epithelium on the anal side or a tumor located entirely on the oral side of the cardia ring, (c) no cancerous changes have occurred in other organs . Most primary adenocarcinomas of the esophagus are derived from BE, ectopic gastric mucosa (EGM), or the esophageal glands [10–12]. In our case, ectopic gastric mucosa was found in the background mucosa of the tumor in the histopathological findings of biopsy before chemotherapy and in the resected specimen, and no abnormal findings were found between the tumor and EGJ. Furthermore, no neoplastic lesions were found in other organs, and the diagnosis was primary cervical to upper thoracic esophageal adenocarcinoma originating from EGM. The relationship between EGM and adenocarcinoma is still unclear, and further studies are needed to investigate their relationship in a larger number of patients . Nomura et al. reviewed the literature on adenocarcinoma arising from ectopic gastric mucosa in the cervical or upper thoracic esophagus . According to their review, majority of the cases were well- or moderately differentiated adenocarcinomas, and only 24.0% of cases were poorly differentiated. Our patient had poorly differentiated adenocarcinoma.
The treatment of cervical esophageal adenocarcinoma is varied. Nomura et al. also reported that treatment strategies depended on the tumor stage: open chest surgery with or without pre/post adjuvant therapy in 37 patients, endoscopic therapy in 8, chemoradiotherapy in 2, and radiation alone in 2 . Moreover, the prognosis for advanced cancer was poor because there was only one survivor of T3-4 . In our department, we usually perform chemoradiotherapy (DF + RT) for unresectable, locally advanced esophageal SCC and achieve good results . However, we usually do not actively administer CRT to esophageal adenocarcinoma, including EGJ. Esophageal adenocarcinomas are less radiosensitive than esophageal squamous cell carcinomas, and all patients who are operable for esophageal adenocarcinoma that is potentially curable should be considered for neoadjuvant chemotherapy or chemoradiotherapy followed by surgery . Since our case was esophageal AC, we considered it important to bring it to radical resection by induction treatment when aiming for a good prognosis. Patients who received induction chemotherapy experienced a trend toward superior survival for not only surgery but also chemoradiotherapy . It was thought that tumor shrinkage due to induction chemotherapy reduces the amount of radiation therapy, and controls micrometastasis. Definitive chemoradiation (DCRT) has been adopted in the treatment of upper esophageal cancers and has become the standard modality recommended by most experts [5, 16]. However, it is controversial, especially for cervical esophageal adenocarcinoma, and local recurrence rates after definitive chemoradiotherapy are high (40–75%) . Moreover, a higher mortality and morbidity rate, including anastomotic leak and pulmonary complications, was reported after salvage surgery [3, 17]. Therefore, we considered that salvage surgery and surgery for recurrent cases after DCRT were technically extremely difficult. From the perspective of prolonging survival, we prioritize surgery for patients who can undergo radical resection.
According to randomized trials, including the OE02 and MAGIC trial, standard chemotherapy is platinum-fluoropyrimidine-based . We usually perform biweekly-DCF (Bi-DCF) chemotherapy for esophageal SCC and EGJ adenocarcinoma with esophageal infiltration, whether it is induction chemotherapy for unresectable or NAC for resectable tumors .We have experienced and reported EGJ adenocarcinoma with pathological CR obtained by radical resection after Bi-DCF chemotherapy . Therefore, we selected Bi-DCF chemotherapy because the regimen was considered effective for rare cases of cervical esophageal adenocarcinoma. As a result, as we aimed, the tumor shrank by induction chemotherapy, the pathological effect of chemotherapy-grade 2 was obtained, and radical resection was possible. Historically, most patients with upper thoracic esophageal cancer were treated by surgery, including pharyngo-laryngo-esophagectomy (PLE) and gastric pull-up. In Japan, we have “Esophageal Cancer Practice Guidelines” for esophageal cancer treatment . In the treatment of cervical esophageal carcinoma, this guideline recommended that we should select chemoradiotherapy or surgery, including laryngectomy, with due consideration given to quality of life. Of course, we chose PLE with the most favorable prognosis after fully explaining that radical resection would cause loss of voice and reduced QOL for this patient.
There are some reports but no clear evidence of success of postoperative adjuvant therapy after radical resection after NAC, as in our case [21–23]. For esophageal SCC, we usually recommend postoperative adjuvant chemotherapy for pathological lymph node metastasis-positive cases because the prognosis of pathological node-positive cases was much worse than that of negative cases. Naoki reported that surgery with pre/postoperative radiation is advisable for the local control of advanced tumors, and surgery with pre/postoperative chemoradiotherapy can prevent both local recurrence and distant metastasis . In our case, the patient was positive for pathological lymph node metastases, but we had undergone maximum surgery followed by NAC, and since the tumor was a rare adenocarcinoma, we decided to follow up closely without adjuvant therapy.
Our patient was a case of highly locally advanced cervical esophageal adenocarcinoma with tracheal infiltration, but induction chemotherapy was effective and radical resection was possible. Cervical esophageal adenocarcinoma was rare, but technically reliable and safe oncologic surgery was possible after induction chemotherapy.