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Salvage esophagectomy with pancreatectomy for local recurrence of thoracic esophageal cancer after definitive chemoradiotherapy: A case report

Highlights • Very little article in literature has been reported the outcome of esophageal cancer patients who underwent esophagectomy with pancreatectomy.• We describe a case of thoracic esophageal cancer in which a relapse occurred in the early postoperative phase, although R0 resection was accomplished by salvage esophagectomy with pancreatectomy.• Because the risk of postoperative complications and relapse is high in patients with advanced esophageal cancer undergoing esophagectomy with pancreatectomy, the applicability of surgery needs to be carefully considered.


Introduction
The effectiveness of salvage surgery for local recurrence after definitive chemoradiotherapy (CRT) for esophageal cancer remains unclear. However, surgical excision is the only curative modality and several studies have reported the effectiveness of salvage surgery for local recurrence after definitive CRT [1][2][3][4].
Here, we describe a case of thoracic esophageal cancer in which a complete response (CR) was achieved after chemoradiotherapy, but lymph node recurrence, with infiltration into the pancreas occurred. Although R0 resection was accomplished by salvage esophagectomy with pancreatectomy, a relapse occurred in the early postoperative phase.
This work has been reported in line with the SCARE criteria [5].

Presentation of case
A 64-year-old man presented with a chief complaint of difficulty with swallowing. He had a history of prostate cancer. The patient's lifestyle included approximately 360 mL sake and 350 mL beer consumption per day, and 20 cigarettes per day for the past 20 years. Upper gastrointestinal endoscopy showed geographic esophageal 0-IIc lesions at 25 cm and 30 cm from the incisors; moreover, a type-2 lesion was observed 35-40 cm from the incisors (Fig. 1a-c). A biopsy confirmed squamous cell carcinoma. On contrast-enhanced computed tomography (CT), the primary lesion in the lower thoracic part of the esophagus demonstrated thickening of the wall all around it. Metastasis was observed in lymph nodes along the right recurrent nerve, left gastric artery, lesser curvature, and around the abdominal aorta. There was a possibility of lymph node infiltration into the pancreas at the lesser curvature lymph node (Fig. 2a). Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed increased FDG uptake in the primary lesion and the lymph node along the left gastric artery (Fig. 2b). The patient was diagnosed with lower intrathoracic esophageal cancer T3N2M1 (LYM) Stage IV (seventh edition of the Union for International Cancer Control system).     Three courses of DCF therapy (intravenous docetaxel and cisplatin infusion with continuous 5-fluorouracil [5-FU]) were administered, and the patient achieved a partial response. Additionally, CRT (intravenous cisplatin infusion with continuous 5-FU, 50.4 Gy/28 Fr for the primary lesion, 29.68 Gy/28 Fr for abdominal lymph nodes) was administered and CR was achieved. At 206 days after completion of CRT, a relapse in the lymph nodes along the lesser curvature, with a possibility of infiltration into the gastric wall and pancreas, was observed on CT and PET images ( Fig. 2c and  d). Therefore, salvage surgery involving a two-stage procedure was selected for treatment. The results of endoscopy indicated that a CR had been maintained (Fig. 1d).
Total gastrectomy, distal pancreatectomy, splenectomy, and then subtotal esophageal resection were performed. Because this was salvage surgery, radical dissection was performed only on the lymph nodes near the esophagus and lymph node along the right recurrent nerve, where metastasis was suspected before preoperative treatment. The surgery was completed after creation of an esophageal fistula and jejunostomy. The second surgery was performed 28 days after the first surgery. Reconstruction of the pedunculated jejunum was performed using an approach through the anterior thoracic wall. The second jejunal artery and vein and right internal thoracic artery and vein were anastomosed to allow for supercharge and superdrainage.
Pathological examination revealed no remnant of the cancer in the primary lesion (therapeutic effect Grade 3). Metastasis was observed in the lesser curvature lymph node, which infiltrated into the gastric wall and pancreas. Therefore, a diagnosis of lower intrathoracic esophageal cancer ypT0N1 (1/7) M0 (Fig. 3) was made. No complication occurred after the first surgery. After the second surgery, however, an anastomotic leak occurred at the site of the esophagojejunostomy and re-anastomosis was performed under local anesthesia.
The patient was discharged from the hospital 62 days after the first surgery. At 195 days after surgery, relapse with hepatic metastasis occurred. Although systemic chemotherapy was administered, the patient died 559 days after surgery.

Discussion
In recent years, as one of the multidisciplinary treatments of esophageal cancer, trimodality therapy comprising surgery, chemotherapy, and radiotherapy has been attracting considerable attention [6]. When patients are administered radical CRT, the rate of CR is approximately 89% in patients with stage I and 63% in patients with stage II/III, respectively [7,8]. Even in patients with T4 tumors and/or M1 lymph node metastasis, 33% have been reported to achieve a CR [9]. Despite the high CR rates, salvage therapy is required in the remaining patients who do not achieve a CR. Moreover, another report suggests that relapse occurs in 40-60% of patients in whom CR is attained [7][8][9][10][11]. Thus, the number of patients who require salvage surgery after radical CRT is expected to increase in the future.
Although the surgical risk of salvage surgery is considered to be extremely high, with high mortality and morbidity rates [4,[12][13][14], selected patients may benefit from highly invasive procedures. Gardner-Thorpe et al. found that salvage esophagectomy for patients with a relapse who initially achieved a CR by CRT achieved long-term survival when R0 resection was performed [15]. Nakajima et al. reported that salvage surgery for recurrent abdominal lymph nodes preserving the esophagus was less invasive and achieved better outcomes when the primary tumor maintained a CR after CRT [3].
To our knowledge, this is the first report of a patient with esophageal cancer who underwent salvage esophagectomy with pancreatectomy. We identified 10 reported cases (Table 1) [16][17][18][19][20][21][22][23][24], including our case, that underwent esophagectomy with pancreatectomy in the Japanese literature. Infiltration of a metastatic lesion into the pancreas was observed in 9 of 10 cases, and the treatment outcome was not favorable. However, Saito et al. reported a long term survivor, therefore a limited number of patients might benefit from those highly invasive operations [20].
In our case, the tumor recurred after definitive CRT, therefore the only chance to achieve a cure was by salvage surgery. Several studies have reported the effectiveness of salvage surgery for recurrent cancer when R0 resection has been achieved [1][2][3][4]. By contrast, other studies have showed only a few patients who could achieve long term survival after esophagectomy with pancreatectomy [16][17][18][19][20][21][22][23][24], therefore careful judgement of the applicability of surgery is required. As for the present case, considering that the primary tumor maintained a CR, salvage surgery preserving the esophagus might be a therapeutic option.

Conclusion
We encountered a case of advanced thoracic esophageal cancer in which R0 resection was attainable by salvage esophagectomy with pancreatectomy after CRT; however, a relapse occurred in the early postoperative phase. Although the treatment outcome of esophagectomy with pancreatectomy has been reported as unfavorable, some patients could achieve long term survival by salvage surgery because of the improvement of trimodality therapy. However, we do not have sufficient evidence to establish indications for this high risk therapy, therefore, careful consideration and judgment on the applicability of surgery is required.

Conflict of interest
The authors have no conflict of interest.

Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval
Given that this is a case report with no identifiable information included in the manuscript, ethical approval has been exempted by our institution.