Elsevier

Surgery

Volume 170, Issue 2, August 2021, Pages 469-477
Surgery

Esophagus
Postoperative pneumonia in the acute phase is an important prognostic factor in patients with esophageal cancer

https://doi.org/10.1016/j.surg.2021.03.051Get rights and content

Abstract

Background

The impact of pneumonia on prognosis is controversial, and no report has focused on its onset. This study aimed to examine the impact of pneumonia according to its onset on prognosis and its associated risk factors after esophagectomy.

Methods

In total, 484 patients who underwent curative resection for esophageal squamous cell carcinoma were retrospectively reviewed. Patients with pneumonia were divided into two groups by the date of onset: pneumonia in the acute phase within 7 days after surgery (n = 59) and pneumonia in the subacute phase 8 days after surgery (n = 49).

Results

The disease-free survival of patients with acute pneumonia was significantly lower than that of those without pneumonia (P = .0002), whereas the disease-free survival of patients with subacute pneumonia was similar to that of patients without pneumonia (P = .5363). In multivariate analysis for disease-free survival, P-stage III to IV (hazard ratio [HR], 3.344; P < .0001), transfusion (HR, 1.4078; P = .0291), and acute pneumonia (HR, 1.8463; P = .0009) were independent prognostic factors. Multivariate analysis revealed that age >75 years (odds ratio [OR], 2.1746; P = .0232), respiratory disease comorbidity (OR, 4.3869; P = .0002), cT3-4 (OR, 2.0143; P = .0477), extended surgery duration (OR, 2.3406; P = .0152), and posterior mediastinal reconstruction (OR, 0.1432; P = .0439) were independent risk factors for acute pneumonia.

Conclusion

Post-esophagectomy pneumonia in the acute phase was an independent prognostic factor, whereas advanced age, respiratory disease comorbidity, and extended surgery duration were risk factors for acute pneumonia.

Introduction

Worldwide, esophageal cancer is the fifth most common cause of cancer-related deaths in men and the eighth in women.1 Despite the development of treatment strategies, the 5-year overall survival (OS) of esophageal cancer is 15% to 35%, and the prognosis remains dismal.2 Although the efficacy of chemotherapy and chemoradiotherapy for esophageal cancer is improving, esophagectomy is still considered the main axis in multimodal treatment. Esophagectomy with a two- to three-field lymph node dissection is a standard procedure for esophageal cancer in Japan and is one of the most invasive surgical treatments among gastrointestinal surgeries. Morbidity after esophagectomy for esophageal squamous cell carcinoma (ESCC) is still high at 50% to 60%, even in high-volume centers and in spite of recently refined operative techniques and improvements of perioperative management. Pneumonia is the most common adverse event in patients with esophageal cancer surgery and the main cause of postoperative hospital deaths.3, 4, 5 Previously, the correlation between postoperative complications and prognosis was investigated in various types of cancer. Some studies reported a correlation between postoperative pneumonia and prognosis in patients receiving esophagectomy, but the mechanism is still unknown. In patients with recurrence after curative resection, it is assumed that micro-metastasis had already occurred at surgery or the tumor spread during surgical manipulation. Some reports suggested that tumor shedding or spillage during surgical manipulation, which were evaluated by squamous cell carcinoma-related antigen and carcinoembryonic antigen mRNA, were associated with recurrence or poor prognosis in ESCC6,7 Fidler (1970) reported that cancer cells injected into the peripheral veins of mice rapidly decreased with time and that they disappeared 7 days after injection,8 which suggested that tumor cells that spread by surgical manipulation needed to survive >7 days. Moreover, inflammation was reported to induce cancer cell proliferation,9 promote the survival of minimal residual cancer cells,10 and lead to escape from immunologic host response,11 which may lead to tumor implantation and growth. Postoperative pneumonia, both in the acute and subacute phases, often occurs after surgery. However, the impact of pneumonia onset on prognosis remains unknown. Based on these findings, we hypothesized that acute phase inflammation owing to postoperative pneumonia can help cells escape apoptosis and promote the implantation and growth of tumor cells, leading to cancer recurrence. This study aimed to examine the impact of pneumonia according to its onset on prognosis, as well as its associated risk factors.

Section snippets

Patients

We retrospectively analyzed data of consecutive patients who were diagnosed with ESCC and underwent transthoracic esophagectomy at the Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, between 2010 and 2016 collected from the hospital database and electronic charts. We excluded patients who had noncurative resection and patients with cervical esophageal cancer who did not undergo transthoracic esophagectomy or who underwent esophagectomy combined with

Patient characteristics

Esophagectomy was performed in 637 ESCC patients between 2010 and 2016; of these, we excluded 45 patients in whom the tumor was located in the cervical esophagus, 51 patients with R1/2 resection, and 17 patients with incomplete follow-up information (mainly because of follow-up at other hospitals). Thus, a total of 484 patients were included from this study. Table 1 shows the baseline characteristics of all included patients in this study: 451 males and 53 females, with a median age of 67 years

Discussion

The present study showed that overall postoperative complications, anastomotic leakage, and wound infection were not associated with poor prognosis, but postoperative pneumonia was associated with poor prognosis. Furthermore, pneumonia in the acute phase after surgery had an impact on OS and recurrence, whereas pneumonia in the subacute phase after surgery had no influence on the prognosis. The impact of postoperative complications on the long-term survival of patients with esophageal cancer

Funding/Support

The authors received no funding.

Conflict of interest/Disclosure

None of the authors have any conflicts of interest ot disclose.

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