How does Surgical Apgar Score predict the short-term complications and long-term prognosis after esophagectomy?

The incidence of esophageal cancer is increasing steadily, which is now the eighth most common malignancy, and its annual amounts have reached nearly half a million (1). Surgical treatment is the cornerstone of curative therapy for esophageal cancer, while this procedure is associated with significant severe complications, whose mortality rate would be the highest among all gastrointestinal surgeries (2). To better the treatment outcomes of esophageal malignancy, Akio Nakagawa and his colleagues provided evidence that the Surgical Apgar Score (SAS) predicts short-term complications and long-term prognosis after an esophagectomy (3). In this study, the sum of the scores of estimated blood loss, lowest mean arterial pressure, and lowest heart rate defined the SAS. A total of 400 patients received surgical treatment were taken into account. Complications achieved the grade-3 level according to the Clavien-Dindo classification, which had occurred in 145 of the cases (36%), which contained 8 cases of surgical mortality, 2 cases of pneumonia, 1 case of an anastomotic leak and 1 case of bronchial fistula. The occurrences of complications were significantly associated with hypertension, thoracotomy, a SAS of less than 5, age (older than 65 years), diabetes, and reconstruction route. Multivariate analysis showed that a SAS of ≤5 was significantly associated with pulmonary and gastrointestinal complication.

Moreover, the survival of patients with cStage 2, 3, or 4 diseases was substantially lower when the SAS was lower than 5 (43.0% vs. 59.7%, P=0.027). As more significant blood loss tended to cause higher heart rates and lower blood pressure, blood loss might be the essential part of determining SAS. Thus, the reason why SAS could predict the incidence of complications and survival after esophagectomy might be attributed mainly to intraoperative blood loss.

It has been reported that postoperative complications lead to a worse prognosis in esophageal cancers (4,5). As Booka et al. said (6), pulmonary infections had a significant negative impact on overall survival (P=0.035), which also had been revealed by multivariate analysis [hazard ratio (HR) 1.456; 95% CI, 1.020–2.079, P=0.039], while anastomotic leakage and recurrent laryngeal nerve paralysis did not affect the survival of patients. Moreover, Baba et al. (7) also reported that patients with pneumonia had a worse long-term prognosis than those without pulmonary infections (HR 1.60, 95% CI, 1.05–2.38, P=0.029). However, surgical site infection, recurrent nerve paralysis, cardiovascular complications, and anastomotic leakage were not in close connections with the long-term prognosis. In the research of Nakagawa et al. (3), thoracotomy (P=0.018), and SAS ≤5 (P=0.01) were in close connection with respiratory complications in the multivariate analysis. Compared with a minimally invasive esophagectomy, thoracotomy tended to gain a higher pain score and result in a more significant blood loss (8). Moreover, the serum C-reactive protein (CRP) level was significantly correlated with intraoperative blood loss, and postoperative complications (9). The preoperative inflammatory response, evaluated by CRP, was reported to increase postoperative recurrence and lead to a reduced survival for various types of cancers (10,11). CRP as well as other serum cytokines or various growth factors, which were combined with systemic inflammation, could lead to proliferation, survival, and migration of cancer cells and even affect the long-term prognosis for the patients (12).

While it is more vulnerable when anastomotic leak might happen, a cervical anastomosis is often adopted for reconstruction after esophagectomy. Although several factors, such as preoperative nutritional status, reconstructed route, and technique of anastomosis, might lead to leakage, ischemia of gastric conduit could be the decisive one (13). Koyanagi et al. (14) used indocyanine green fluorescence to assess blood flow speed of the gastric tube, which showed that the blood flow speed was not associated with the connection of arterial arch but intraoperative blood loss. Once the intraoperative blood loss caused temporary lower blood pressure, ischemia or even leakage might occur. Nakagawa et al. (3) also reported that a SAS of ≤5 (P=0.035) was significantly correlated with gastrointestinal complication.

Improved perioperative management, skilled surgical techniques, and careful postoperative care have reduced the mortality and morbidity rates, especially in high volume centers (15). As treatment has evolved, the demand for proper meaningful prognostic tools is nonnegligible. A prognostic tool based on the accurate prediction of short-term complications and long-term prognosis in patients with esophageal carcinoma helps surgeon choose optimal treatment. However, the quality of a useful device should be examined by some model performance measures, including calibration, discrimination, and clinical usefulness (16). A calibration plot, which is summarized from the correspondence between outcomes and predictions, means calibration. And the ability how well a prediction model can distinguish those with the result from those without the result is defined as discrimination. Moreover, the usefulness of a prediction model is approved when better decisions are made with the model than without it. Although SAS has been proven to predict the complications and long-term survival rates after surgery, its calibration, discrimination, and clinical usefulness remain undefined.

The substantial benefit of this research revealed that SAS could predict short-term as well as long-term prognosis. However, if the calibration, discrimination, and clinical usefulness of the SAS could be further verified, this method could become more applicable.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

References

1. Jemal A, Murray T, Samuels A, et al. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5-26. [Crossref] [PubMed]
2. Markar SR, Karthikesalingam A, Thrumurthy S, et al. Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis 2000-2011. J Gastrointest Surg 2012;16:1055-63. [Crossref] [PubMed]
3. Nakagawa A, Nakamura T, Oshikiri T, et al. The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy. Ann Surg Oncol 2017;24:3934-46. [Crossref] [PubMed]
4. Ferri LE, Law S, Wong KH, et al. The influence of technical complications on postoperative outcome and survival after esophagectomy. Ann Surg Oncol 2006;13:557-64. [Crossref] [PubMed]
5. Carrott PW, Markar SR, Kuppusamy MK, et al. Accordion severity grading system: assessment of relationship between costs, length of hospital stay, and survival in patients with complications after esophagectomy for cancer. J Am Coll Surg 2012;215:331-6. [Crossref] [PubMed]
6. Booka E, Takeuchi H, Nishi T, et al. The Impact of Postoperative Complications on Survivals After Esophagectomy for Esophageal Cancer. Medicine (Baltimore) 2015;94:e1369. [Crossref] [PubMed]
7. Baba Y, Yoshida N, Shigaki H, et al. Prognostic Impact of Postoperative Complications in 502 Patients With Surgically Resected Esophageal Squamous Cell Carcinoma: A Retrospective Single-institution Study. Ann Surg 2016;264:305-11. [Crossref] [PubMed]
8. Biere SS, van Berge Henegouwen MI, Maas KW, et al. Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet 2012;379:1887-92. [Crossref] [PubMed]
9. Koyanagi K, Ozawa S, Tachimori Y. Minimally invasive esophagectomy in the prone position improves postoperative outcomes: role of C-reactive protein as an indicator of surgical invasiveness. Esophagus 2018;15:95-102. [Crossref] [PubMed]
10. Roxburgh CS, Salmond JM, Horgan PG, et al. Comparison of the prognostic value of inflammation-based pathologic and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer. Ann Surg 2009;249:788-93. [Crossref] [PubMed]
11. Forrest LM, McMillan DC, McArdle CS, et al. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer 2003;89:1028-30. [Crossref] [PubMed]
12. Germano G, Allavena P, Mantovani A. Cytokines as a key component of cancer-related inflammation. Cytokine 2008;43:374-9. [Crossref] [PubMed]
13. Walther B, Johansson J, Johnsson F, et al. Cervical or thoracic anastomosis after esophageal resection and gastric tube reconstruction: a prospective randomized trial comparing sutured neck anastomosis with stapled intrathoracic anastomosis. Ann Surg 2003;238:803-12; discussion 812-4. [Crossref] [PubMed]
14. Koyanagi K, Ozawa S, Oguma J, et al. Blood flow speed of the gastric conduit assessed by indocyanine green fluorescence: New predictive evaluation of anastomotic leakage after esophagectomy. Medicine (Baltimore) 2016;95:e4386. [Crossref] [PubMed]
15. Ruol A, Castoro C, Portale G, et al. Trends in management and prognosis for esophageal cancer surgery: twenty-five years of experience at a single institution. Arch Surg 2009;144:247-54; discussion 254. [Crossref] [PubMed]
16. Steyerberg EW, Vergouwe Y. Towards better clinical prediction models: seven steps for development and an ABCD for validation. Eur Heart J 2014;35:1925-31. [Crossref] [PubMed]