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Journal of Peking University (Health Sciences) ›› 2026, Vol. 58 ›› Issue (3): 567-574. doi: 10.19723/j.issn.1671-167X.2026.03.017

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Perioperative hyperglycemia predicts poorer prognosis of esophageal squamous cell carcinoma patients treated with esophagectomy

Bo PENG1, Fangfang LIU1, Wei YANG2, Ruiping XU3, Lei CHEN2, Baozhong LI3, Xinjia WANG2, Ji KE1, Wenlei YANG1, Yu HE4, Zhen LIU1, Bolin HOU5, Liqun ZHANG2, Miaoping LIN2, Lixin ZHANG3, Fan ZHANG2, Fen CAI2, Huawen XU2, Mengfei LIU1, Ying LIU1, Yaqi PAN1, Zhonghu HE6,*(), Yang KE6,*()   

  1. 1. Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing 100142, China
    2. Cancer Hospital of Shantou University Medical College, Shantou 515031, Guangdong, China
    3. Anyang Cancer Hospital, Anyang 455000, Henan, China
    4. Chinese Preventive Medicine Association, Beijing 100062, China
    5. Linkdoc AI Research(LAIR), Beijing 100080, China
    6. State Key Laboratory of Molecular Oncology, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing 100142, China
  • Received:2026-02-24 Online:2026-06-18 Published:2026-04-10
  • Contact: Zhonghu HE, Yang KE
  • About author:

    * These authors contributed equally to this work

  • Supported by:
    the National Key R&D Program of China(2021YFC2500405)

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Abstract:

Objective: To systematically evaluate the association between perioperative hyperglycemia and postoperative prognosis in esophageal squamous cell carcinoma (ESCC) patients using large-scale, multicenter real-world data. Methods: A total of 5 952 patients with ESCC who underwent radical esophagectomy were consecutively included in this retrospective cohort study from the Anyang Cancer Hospital in Anyang, Henan Province (January 2012 to December 2017) and the Cancer Hospital of Shantou University Medical College in Shantou, Guangdong Province (August 2009 to December 2018). Perioperative fasting glucose data were obtained from the hospital information system. The perioperative period was divided into preoperative and postoperative phases: Preoperative hyperglycemia was defined as a mean fasting glucose level ≥7.0 mmol/L from day 14 to day 2 before surgery, and postoperative hyperglycemia was defined as a mean fasting glucose level ≥7.0 mmol/L from day 2 to day 14 after surgery. The primary outcome was overall survival (OS), and secondary outcomes included 30 d/90 d postoperative mortality and in-hospital complications. Multivariable Cox proportional hazards models were used to assess the association between perioperative hyperglycemia and OS, with adjusted hazard ratios (HR) and 95% confidence intervals (CI) calculated. Results: The maximum follow-up period was 12 years. The prevalence of preoperative and postoperative hyperglycemia was 6.7% and 18.3%, respectively. Patients with preoperative hyperglycemia had a lower 5-year OS rate than those without (57.3% vs. 65.0%), with an adjusted HR of 1.41 (95%CI: 1.19-1.68). The patients with postoperative hyperglycemia also had reduced 5-year survival (61.8% vs. 66.4%), with an adjusted HR of 1.39 (95%CI: 1.22-1.58). Joint analysis showed that compared with patients without hyperglycemia, those with hyperglycemia in either the preoperative or postoperative phase alone had an elevated mortality risk (HR=1.24, 95%CI: 1.07-1.43), while the patients with hyperglycemia in both phases had the highest mortality risk (HR=1.86, 95%CI: 1.49-2.32). Stratified analysis revealed that BMI significantly modified the association between hyperglycemia and adverse prognosis (Pinteraction=0.010), with the association being particularly pronounced in patients with BMI ≥24.0 kg/m2. Additionally, perioperative hyperglycemia was associated with poorer short-term postoperative outcomes. Conclusion: Perioperative hyperglycemia is an independent risk factor for long-term survival in ESCC patients undergoing curative esophagectomy. These findings suggest that enhanced routine glucose monitoring and control during perioperative management of ESCC may help improve long-term patient outcomes.

Key words: Perioperative hyperglycemia, Diabetes, Prognosis, Complications, Esophageal squamous cell carcinoma

CLC Number: 

  • R735.1

Table 1

Selected characteristics of ESCC patients who underwent radical esophagectomy, stratified by perioperative glucose status"

Characteristics Total(n=5 952) Preoperative hyperglycemiaa Postoperative hyperglycemiaa
No (n=5 341) Yes (n=381) P valueb No (n=3 796) Yes (n=848) P valueb
Age/years 63.0 (58.0, 68.0) 63.0 (58.0, 68.0) 64.0 (60.0, 68.0) 0.018 64.0 (59.0, 68.0) 65.0 (60.5, 70.0) < 0.001
Gender < 0.001 < 0.001
  Male 3 840 (64.5) 3 482 (94.6) 197 (5.4) 2 515 (85.3) 433 (14.7)
  Female 2 112 (35.5) 1 859 (91.0) 184 (9.0) 1 281 (75.5) 415 (24.5)
Smokingc < 0.001 < 0.001
  No 2 719 (46.8) 2 385 (91.4) 224 (8.6) 1 710 (77.3) 503 (22.7)
  Yes 3 086 (53.2) 2 827 (95.2) 144 (4.8) 1 978 (86.1) 320 (13.9)
Drinkingc 0.042 < 0.001
  No 3 762 (65.5) 3 349 (92.9) 257 (7.1) 2 386 (80.2) 589 (19.8)
  Yes 1 980 (34.5) 1 805 (94.3) 109 (5.7) 1 253 (84.8) 224 (15.2)
BMI/(kg/m2)c < 0.001 < 0.001
   < 24.0 3 337 (70.0) 3 068 (95.2) 153 (4.8) 2 050 (85.0) 361 (15.0)
  ≥ 24.0 1 431 (30.0) 1 224 (89.6) 142 (10.4) 900 (76.4) 278 (23.6)
pStageb 0.822 0.102
  0 andⅠ 1 356 (22.9) 1 206 (93.1) 89 (6.9) 910 (79.6) 233 (20.4)
  Ⅱ 2 401 (40.6) 2 162 (93.6) 149 (6.4) 1 592 (82.1) 347 (17.9)
  Ⅲ 2 157 (36.5) 1 939 (93.1) 143 (6.9) 1 267 (82.7) 265 (17.3)
Center 0.021 0.065
  Northern 4 001 (67.2) 3 562 (92.8) 276 (7.2) 2 891 (81.2) 671 (18.8)
  Southern 1 951 (32.8) 1 779 (94.4) 105 (5.6) 905 (83.6) 177 (16.4)

Figure 1

Kaplan-Meier survival curves for long-term OS by perioperative glucose status among ESCC patients who underwent radical esophagectomy OS, overall survival; ESCC, esophageal squamous cell carcinoma."

Figure 2

Association of high perioperative glucose levels, defined using different cutoffs, with long-term OS of ESCC patients who underwent radical esophagectomy Different cutoffs of glucose levels (from 5.0 to 11.0 mmol/L with an increment of 1.0 mmol/L) were used to divide patients into high and low-to-normal levels of blood glucose concentrations. HR and 95% CI representing the survival effect of high postoperative (red lines) and preoperative (blue lines) glucose levels as compared with low-to-normal glucose levels were obtained using multivariable Cox proportional-hazard models adjusting for age, gender, smoking, alcohol consumption, body mass index, presence of comorbidities, tumor location, tumor morphology, pathological tumor-lymph node-metastasis (pTNM) stage, tumor grade, tumor size, number of lymph nodes harvested, surgical margin status, calendar year of operation, and center. CI, confidence interval; ESCC, esophageal squamous cell carcinoma; HR, hazard ratio; OS, overall survival."

Table 2

Dose-response relationship of perioperative glucose levels with long-term OS among ESCC patients who underwent radical esophagectomy"

Glucose levels/(mmol/L) Total，n (%) Death，n (%) 5-year survival/% (95%CI) Adjusted HR (95%CI)a P valuea
Preoperative
   < 7.0 4 441 (93.3) 1 667 (37.5) 66.5 (64.8-68.1) Reference
  7.0- < 11.0 271 (5.7) 126 (46.5) 56.7 (51.0-63.2) 1.40 (1.17-1.69) < 0.001
  ≥ 11.0 50 (1.1) 21 (42.0) 60.6 (48.3-76.2) 1.47 (0.95-2.27) 0.081
  Ptrend < 0.001
Postoperative
   < 7.0 3 097 (81.3) 1 086 (35.1) 66.4 (64.7-68.2) Reference
  7.0- < 11.0 668 (17.5) 267 (40.0) 63.0 (59.3-66.9) 1.35 (1.18-1.55) < 0.001
  ≥ 11.0 44 (1.2) 26 (59.1) 43.4 (30.5-61.7) 1.98 (1.34-2.94) 0.001
  Ptrend < 0.001

Figure 3

Subgroup analysis of the associations between perioperative glucose levels and long-term OS among ESCC patients who underwent radical esophagectomy HR and 95% CI were obtained using multivariable Cox proportional-hazard models, adjusting for age, sex, smoking, alcohol consumption, body mass index (BMI), presence of comorbidities, tumor location, tumor morphology, pathological tumor-lymph node-metastasis (pTNM) stage, tumor grade, tumor size, margin status, postoperative treatment modality, calendar year of operation, and study center. The multiplicative interaction between hyperglycemia and each one of the stratified factors was evaluated by including an interaction term in the multivariable Cox proportional-hazard regression model. Both preoperative and postoperative hyperglycemia were defined as mean glucose levels ≥ 7.0 mmol/L (126 mg/dL). Perioperative glucose status was categorized as "Neither" (with no hyperglycemia), "Either" (with preoperative or postoperative hyperglycemia alone), and "Both" (with both preoperative and postoperative hyperglycemia). CI, confidence interval; ESCC, esophageal squamous cell carcinoma; HR, hazard ratio; OS, overall survival."

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