Author: Laurence Weinberg, et al.
Cureus, July 5, 2026
Postoperative complications are traditionally viewed as short-term events that increase hospital length of stay, cost, and early mortality. This narrative review argues that complications may also trigger biological changes that continue long after the patient appears to have recovered and may contribute to reduced long-term survival.
The authors reviewed 84 clinical, translational, and experimental studies involving oncological and non-oncological surgery. Four recurring pathways were identified: persistent systemic inflammation, exaggerated neuroendocrine stress, perioperative immune dysfunction, and disruption of adjuvant cancer treatment.
Persistent systemic inflammation
Surgery normally produces a temporary inflammatory response involving tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and C-reactive protein.
When complications such as pneumonia, sepsis, wound infection, or anastomotic leakage occur, this inflammatory response may become more intense and prolonged.
Sustained inflammation may contribute to:
• Endothelial dysfunction
• Myocardial and vascular injury
• Accelerated atherosclerosis
• Mitochondrial dysfunction
• Impaired tissue repair
• Progressive organ dysfunction
• Persistent disability and reduced long-term survival
The review emphasizes that postoperative complications may not merely identify patients who were already sicker. They may actively amplify inflammatory processes that influence later cardiovascular events and mortality.
Neuroendocrine stress response
Surgery activates the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, increasing circulating catecholamines and glucocorticoids.
Complicated postoperative recovery may prolong this stress response. Experimental evidence suggests that beta-adrenergic stimulation can promote:
• Tumor-cell proliferation
• Angiogenesis
• Cellular migration and invasion
• Lymphatic remodeling
• Formation of metastatic niches
• Increased susceptibility to tumor dissemination
These findings raise the possibility that prolonged sympathetic activation following postoperative complications may contribute to cancer recurrence, although much of the evidence remains preclinical.
Perioperative immune dysfunction
Major surgery temporarily suppresses cell-mediated immunity. Reported changes include:
• Reduced natural killer-cell activity
• Reduced cytotoxic CD8-positive T-cell function
• Expansion of regulatory T cells
• Shifting from antitumor T-helper-1 responses toward T-helper-2 responses
• Macrophage polarization toward tumor-promoting phenotypes
Postoperative complications may extend this period of immune vulnerability. In cancer patients, impaired immune surveillance could reduce the body’s ability to eliminate residual malignant cells or early metastatic deposits.
In non-cancer patients, immune dysfunction may increase susceptibility to infection, delay recovery, and contribute to persistent organ injury.
Postoperative complications and cancer progression
Infectious complications after cancer surgery have been associated with increased recurrence and reduced survival in several malignancies, including colorectal, gastric, lung, breast, and head and neck cancers.
Potential mechanisms include increased production of:
• Interleukin-6
• Vascular endothelial growth factor
• Matrix metalloproteinases
• Prostaglandin E2
• Cyclooxygenase-2-related signaling molecules
These mediators may support angiogenesis, tumor-cell adhesion, cancer stem-cell expansion, invasion, and metastatic spread.
The review also discusses evidence that beta-blockers, cyclooxygenase-2 inhibitors, and anti-inflammatory medications may modify some of these pathways. However, current clinical evidence is insufficient to recommend their routine use specifically to prevent postoperative cancer recurrence.
Disruption of adjuvant cancer treatment
Major postoperative complications may delay or prevent chemotherapy or radiation therapy by causing:
• Prolonged hospitalization
• Reoperation
• Readmission
• Functional decline
• Malnutrition
• Reduced ability to tolerate treatment
The importance of this pathway varies according to cancer type, stage, treatment regimen, and severity of the complication.
Anastomotic leakage following colon cancer surgery, for example, has been associated with a reduced likelihood of receiving adjuvant chemotherapy and a longer delay before treatment begins.
However, the relationship is not consistent across all cancers, so treatment disruption should be viewed as a context-dependent mechanism rather than a universal explanation.
Clinical implications
The review reframes postoperative complications as biologically important events rather than isolated short-term outcomes.
Preventing complications may potentially improve more than hospital efficiency and 30-day outcomes. It may also reduce persistent inflammation, immune suppression, cardiovascular injury, cancer progression, and long-term mortality.
Patients who develop major complications may benefit from:
• More intensive recovery surveillance
• Early treatment of infection and organ dysfunction
• Attention to persistent inflammatory abnormalities
• Cardiovascular risk assessment
• Nutritional and functional rehabilitation
• Timely coordination of oncology treatment
• Longer-term follow-up after discharge
Important limitations
This was a narrative review rather than a formal systematic review or meta-analysis.
No formal risk-of-bias assessment or evidence grading was performed.
The included studies were highly heterogeneous and involved different operations, complication definitions, patient populations, follow-up periods, and long-term outcomes.
Many proposed mechanisms are supported primarily by laboratory, animal, translational, or observational evidence. Therefore, the review establishes biological plausibility but does not prove that postoperative complications directly cause reduced long-term survival.
Bottom line
Postoperative complications are consistently associated with reduced long-term survival after both cancer and non-cancer surgery.
Persistent inflammation, prolonged neuroendocrine stress, impaired immune surveillance, and delays in adjuvant treatment provide plausible explanations for this relationship.
The findings suggest that the perioperative period may represent an important therapeutic opportunity. Preventing complications and rapidly limiting their biological consequences could potentially improve not only immediate recovery but also long-term cardiovascular, oncological, and survival outcomes.
Thank you to Cureus for allowing us to summarize this narrative review.