Esophageal cancer is an aggressive disease because it widely metastasizes from neck to abdomen even in its early stage. Neoadjuvant treatment followed by surgery has been a standard worldwide for improving treatment outcome, and we are currently running a three‐arm phase III trial to evaluate the superiority of neoadjuvant triplet chemotherapy using docetaxel, cisplatin, and fluorouracil over cisplatin and fluorouracil (CF) as well as the superiority of neoadjuvant CF radiation over CF. Despite advances in multidisciplinary treatment, transthoracic esophagectomy (TTE) has been the mainstay in curative treatment. TTE was recognized as a highly invasive treatment procedure with high mortality rate. Takeuchi et al reviewed the Japanese National Clinical Database (NCD) and reported a 30‐day mortality of 1.2% in 2011. 1 More recently, Yoshida et al conducted an updated analysis based on NCD data from 2012 to 2016, and showed that 30‐day mortality was 0.8% and 2.1% upon discharge, respectively. 2 Although further improvement is needed, the current update analysis indicated the remarkable decrease in mortality.
One of the leading causes of postoperative mortality has been pulmonary complication, which was reported to have an incidence of 16.9% in recent NCD data. In the present issue of Annals of Gastroenterological Surgery, Yoshida et al reviewed the risk factors and proposed several approaches for preventing the onset of pulmonary complications. 3 As promising tactics, they suggested preoperative smoking cessation, respiratory rehabilitation, maintaining oral hygiene, perioperative nutritional intervention, enforcement of less invasive surgery, perioperative administration of steroids, and comprehensive management by a multidisciplinary team. As described in the manuscript, accumulation of the latest information on risk assessment and multidisciplinary approaches for the prevention of pulmonary morbidity is required for further improvement of surgical outcomes post esophagectomy.
In addition to the short‐term unfavorable outcomes, pulmonary complications were reported to lead to cancer recurrence and affect long‐term outcomes after TTE. Severe infectious pulmonary complications could lead to immunosuppression, and prolonged hospitalization is associated with sarcopenia and nutritional deficiency, which could result in cancer recurrence. Furthermore, postoperative systemic inflammatory response proved to be a negative prognostic factor due to the direct proliferation of cancer cells caused by inflammatory signaling and immunosuppression in the tumor microenvironment. More recently, Shimada et al conducted a comprehensive meta‐analysis to evaluate the correlation between postoperative complications and prognosis in various types of cancer surgery. 4 They concluded that postoperative complications after radical surgery for esophageal, gastric, and colorectal cancers were associated with patient prognosis and avoiding such complications might improve the outcomes. These results were supported by a French randomized control trial in which hybrid minimally invasive esophagectomy (MIE, laparoscopic gastric mobilization, and open thoracotomy) with open esophagectomy (open gastric mobilization and thoracotomy) was conducted and proved the short‐term benefit of minimally invasive esophagectomy with lower incidence of pulmonary complications. They demonstrated that overall survival and disease‐free survival tended to be longer in the MIE group than in the open group but the difference was not significant. 5
Overall, we need to strive to avoid postoperative complications. Although still immature, direct intervention in postoperative inflammatory response and coagulopathy has been tested to improve long‐term outcomes. Development of minimally invasive surgery with less pulmonary complications along with direct intervention in postoperative inflammatory response and coagulopathy could be a new approach to improving long‐term outcome in esophageal cancer patients.
DISCLOSURE
Conflict of Interest: Yuko Kitagawa received lecture fees from Asahi KASEI Co., Ltd., TAIHO PHARMACEUTICAL CO., LTD, CHUGAI PHARMACEUTICAL CO., LTD., EA Pharma Co., Ltd., Yakult Honsha Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Factory Inc, SHIONOGI & CO., LTD., Astellas Pharma Inc, DAINIPPON SUMITOMO PHARMA Co., Ltd., Taisho Toyama Pharmaceutical Co., ONO PHARMACEUTICAL CO., NIHON PHARMACEUTICAL CO., LTD., Sanofi KK, Eisai Co., Ltd., KAKEN PHARMACEUTICAL CO.,LTD.. Yuko Kitagawa received research expenses, scholarship donations (grants) from Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Yakult Honsha Co. Ltd., Daiichi Sankyo Co., Ltd., Merck Serono Co., Ltd., Asahi Kasei Co., Ltd., EA Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Factory Inc, Shionogi Co., Ltd., Kaken Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co., Ltd., Astellas Pharma Inc, Medicon Inc, Dainippon Sumitomo Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Kyouwa Hakkou Kirin Co., Ltd., Pfizer Japan Inc, Ono Pharmaceutical Co., Ltd., Nihon Pharmaceutical Co., Ltd., Japan Blood Products Organization Medtronic Japan Co., Ltd., Sanofi KK, Eisai Co., Ltd., Tsumura & Co., Ltd., KCI Licensing, Inc, Abbott Japan Co., Ltd., FUJIFILM, Toyama Chemical Co., Ltd. Yuko Kitagawa worked as a director of endowed chair supported from TAIHO PHARMACEUTICAL CO., LTD, CHUGAI PHARMACEUTICAL CO., LTD..
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