Esophagectomy using thoracoscopy and/or laparoscopy, the so-called minimally invasive esophagectomy (MIE), is increasingly performed worldwide. According to a recent review article, the incidence rates of postoperative complications after MIE, such as pneumonia, arrhythmia, anastomotic leakage, and recurrent laryngeal nerve palsy, are approximately 10% each . Salvage esophagectomy is performed in patients with remaining or recurrent ESCC after dCRT and is associated with high rates of morbidity and mortality. Watanabe et al. reported that postoperative complications occurred in 65.1% of patients; the mortality rate was 7.9% . In recent years, MIE as salvage surgery has also been performed; Takemura et al. performed salvage thoracoscopic esophagectomy following dCRT in 27 patients without serious perioperative complications . In general, thoracoscopic esophagectomy presents a number of advantages, such as magnification effect and good lightning, although it remains technically demanding and associated with a significant operator learning curve . In this case, thoracoscopic esophagectomy was carried out as a salvage treatment after CIRT without any perioperative complications. Salvage MIE after CIRT may be an option for esophageal resection.
Although several studies have demonstrated the treatment efficacy of CIRT for ESCC [5, 6], no case of salvage esophagectomy following CIRT has yet been published. Thus, the impact of CIRT on esophageal surgery remains unclear. In a mouse model, Cui et al. reported that irradiation using carbon ions induced more severe xenograft tumor fibrosis than did X-rays . Ohtaki et al. showed that CIRT resulted in strong fibrosis and adhesion inside the therapeutic dose irradiation field in patients with lung cancer . In their study, five of the six patients with lung cancer required a combined resection, which would not be necessary before CIRT given the presence of strong adhesions and the possibility of tumor extension. According to these previous reports, CIRT may induce more severe fibrosis of irradiated tissues than X-rays. However, it is difficult to declare whether X-rays or CIRT causes stronger fibrosis of esophageal cancer with only our one case. An accumulation of additional cases is needed to determine whether X-rays or CIRT induces more severe fibrosis in patients with esophageal cancer. In our study, we dissected the adhesion between the esophagus and the surrounding organs by thoracoscopic surgery. However, pathological examinations revealed severe fibrosis of the previously irradiated tissues compared to the normal esophagus located outside of the irradiation field (Fig. 4d, e). To minimize damage to other organs, it is necessary to identify which organs should or should not be preserved, and then separate them carefully.
There have been no randomized trials comparing clinical results of X-rays and CIRT. It is difficult to discuss the therapeutic results of CIRT when compared with those of X-rays because there have been few reports on their treatment outcomes and the number of cases treated is small. Enrollment for a phase I/II clinical trial of CIRT for patients with clinical stage I ESCC (UMIN000013552) has already been completed and the results of the analysis are awaited.
Prior to surgery, we found that the tumor had infiltrated the submucosal layer according to the endoscopic ultrasonography (EUS) findings. However, a pathological examination revealed that the tumor was located in the LPM. Typically, it remains difficult to accurately predict the depth of the tumor following irradiation due to tissue fibrosis. Griffin et al. showed that the accuracy rate of EUS for esophageal cancer following neoadjuvant chemoradiotherapy was 36% . Although it remains unknown whether EUS can diagnose the depth of the tumor after CIRT, we believe that EUS after CIRT is also less accurate after chemoradiotherapy. However, an endoscopic resection was difficult to perform because the tumor was located on the scar. We believe that radical esophagectomy as a salvage treatment was indispensable in this case.
In this case, 6 years after CIRT, a new esophageal cancer developed at the site of the primary tumor. It remains unknown whether a newly appearing cancer is a recurrent primary tumor or metachronous disease. Since we did not perform a genomic analysis, it was difficult to correctly answer this oncological question. However, Xi et al. reported that 88.3% of recurrences after chemoradiotherapy in patients with esophageal cancer occurred within 2 years . We speculate that a metachronous tumor freshly appeared 6 years after CIRT in our case. It remains unclear whether CIRT for esophageal cancer increases the risk of subsequent primary cancer. However, CIRT can show high local control rates and achieve long-term survival. Long-term follow-up is desirable after CIRT in patients with esophageal cancer.