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Research Article | Volume 15 Issue 3 (March, 2025) | Pages 878 - 881
Pathological Assessment of Post-Surgical Inflammatory Responses: Implications for Wound Healing and Surgical Outcomes
 ,
 ,
1
Assistant Professor, Department of General Surgery, Government Medical College, Surat, Gujarat, India
2
MBBS DGO, Department Obstetrics and Gynaecology, Government Multi-Speciality Hospital, Chandigarh, India
Under a Creative Commons license
Open Access
Received
Feb. 17, 2025
Revised
Feb. 27, 2025
Accepted
March 7, 2025
Published
March 29, 2025
Abstract

Background:  Post-surgical inflammatory responses significantly influence wound healing and overall surgical outcomes. Understanding the pathological mechanisms underlying these inflammatory processes is crucial for optimizing patient recovery and minimizing complications. This study aims to assess the intensity and characteristics of post-surgical inflammatory responses and their implications for wound healing and surgical outcomes. Materials and Methods: A prospective study was conducted involving 60 patients undergoing elective surgeries across various surgical specialties. Blood samples and tissue biopsies were collected at baseline (pre-surgery), 24 hours, 72 hours, and 7 days post-surgery. Histopathological analysis, inflammatory biomarker assays (C-reactive protein, IL-6, TNF-α), and wound healing assessments were performed. Inflammatory response scores were calculated based on cellular infiltration, edema, and tissue necrosis. Statistical analysis was conducted using ANOVA and Pearson's correlation to determine associations between inflammatory markers and wound healing efficiency. Results: Patients exhibited a significant elevation in inflammatory biomarkers post-surgery, with peak levels recorded at 24 hours (CRP: 35.2 ± 6.1 mg/L, IL-6: 90.4 ± 12.5 pg/mL, TNF-α: 65.7 ± 8.9 pg/mL). Histopathological analysis revealed substantial neutrophil infiltration and tissue edema within the first 72 hours, gradually transitioning to macrophage-dominant infiltration by day 7. Patients exhibiting lower inflammatory marker levels (CRP < 25 mg/L, IL-6 < 70 pg/mL, TNF-α < 50 pg/mL) demonstrated superior wound healing scores (P < 0.05) compared to those with higher levels. A positive correlation was observed between elevated inflammatory markers and delayed wound healing. Conclusion: The intensity of post-surgical inflammatory responses plays a pivotal role in determining wound healing efficiency and surgical outcomes. Elevated levels of inflammatory biomarkers are associated with delayed healing and increased complication rates. Targeted interventions to modulate inflammation may improve surgical recovery and patient outcomes.

Keywords
INTRODUCTION

Post-surgical inflammation is a critical physiological response that plays a fundamental role in wound healing and tissue repair. The inflammatory phase, characterized by the activation and infiltration of leukocytes, primarily neutrophils and macrophages, aims to eliminate pathogens, clear necrotic tissue, and initiate tissue regeneration (1). While a certain level of inflammation is necessary for effective healing, excessive or prolonged inflammatory responses can adversely affect wound healing, leading to chronic inflammation, impaired tissue repair, and increased susceptibility to post-operative complications (2).

 

Various inflammatory biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been extensively studied for their roles in mediating the inflammatory response following surgery (3). Elevated levels of these biomarkers are often associated with poor wound healing outcomes and the development of complications such as infection, fibrosis, and delayed tissue regeneration (4).

 

Recent studies have highlighted the importance of modulating the inflammatory response to improve post-surgical recovery. Strategies such as anti-inflammatory therapies, enhanced surgical techniques, and optimizing perioperative care have been proposed to reduce excessive inflammation and improve healing outcomes (5). However, the complex interplay between inflammation and wound healing necessitates further investigation to establish targeted interventions that can effectively promote tissue repair and reduce complications.

 

The present study aims to assess the pathological characteristics of post-surgical inflammatory responses, focusing on their implications for wound healing and surgical outcomes. By evaluating histopathological changes and quantifying inflammatory biomarkers, this study seeks to elucidate the correlation between inflammatory responses and wound healing efficiency. Understanding these associations may contribute to the development of improved therapeutic strategies for enhancing post-surgical recovery.

MATERIALS AND METHODS

Study Design and Population:

This prospective study was conducted on 60 patients undergoing elective surgeries from various surgical specialties at a tertiary care hospital. Patients aged 18–65 years, with no history of autoimmune disorders, diabetes, or other chronic inflammatory conditions, were included. Informed consent was obtained from all participants.

 

Sample Collection:

Blood samples and tissue biopsies were collected from each patient at four time points: baseline (pre-surgery), 24 hours post-surgery, 72 hours post-surgery, and 7 days post-surgery. Blood samples were collected via venipuncture and immediately processed for serum extraction, while tissue biopsies were obtained from the surgical wound margins during routine dressing changes under aseptic conditions.

 

Inflammatory Biomarker Analysis:

Serum levels of inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were measured using enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer’s instructions. The sensitivity and specificity of each assay were validated before the commencement of the study.

 

Histopathological Analysis:

Tissue samples were fixed in 10% formalin, embedded in paraffin, sectioned at 5 μm thickness, and stained with hematoxylin and eosin (H&E). The stained sections were examined under a light microscope to evaluate inflammatory cell infiltration, tissue edema, and the presence of necrosis. A semi-quantitative scoring system (0–3) was used to assess the severity of inflammation.

 

Wound Healing Assessment:

Wound healing was evaluated based on clinical parameters, including wound size reduction, exudate levels, and tissue granulation, at each time point. Additionally, a scoring system was employed to categorize healing efficiency as excellent, moderate, or poor.

 

Statistical Analysis:

Statistical analysis was performed using SPSS software (version 26.0). Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables were presented as frequencies and percentages. Differences between groups were assessed using Analysis of Variance (ANOVA) followed by post-hoc analysis where applicable. Pearson’s correlation was used to determine the association between inflammatory marker levels and wound healing scores. A p-value of <0.05 was considered statistically significant.

RESULTS

The results of the study are presented in tables demonstrating the levels of inflammatory biomarkers, histopathological scoring, and wound healing assessment at various time points.

 

Inflammatory Biomarker Levels:

Serum levels of CRP, IL-6, and TNF-α were measured at baseline, 24 hours, 72 hours, and 7 days post-surgery. The values indicated a significant increase in all biomarkers at 24 hours, followed by a gradual decline over the subsequent days.

 

Table 1: Inflammatory Biomarker Levels at Different Time Points

Time Point

CRP (mg/L)

IL-6 (pg/mL)

TNF-α (pg/mL)

Baseline

4.2 ± 1.1

12.5 ± 2.3

10.7 ± 1.9

24 Hours

35.2 ± 6.1

90.4 ± 12.5

65.7 ± 8.9

72 Hours

22.7 ± 5.2

60.1 ± 9.7

40.5 ± 7.2

7 Days

10.3 ± 3.5

25.6 ± 6.3

18.9 ± 4.0

 

The peak values for all biomarkers were observed at 24 hours post-surgery, with CRP showing a significant decrease by 72 hours and nearing baseline by 7 days (Table 1).

 

Histopathological Scoring:

Histopathological analysis of tissue biopsies revealed varying levels of inflammation, tissue edema, and necrosis at different time points.

 

Table 2: Histopathological Scoring of Inflammatory Response

Time Point

Neutrophil Infiltration (0–3)

Edema (0–3)

Tissue Necrosis (0–3)

Baseline

0.5 ± 0.2

0.4 ± 0.1

0.2 ± 0.1

24 Hours

2.8 ± 0.4

2.7 ± 0.5

1.9 ± 0.3

72 Hours

2.0 ± 0.3

1.8 ± 0.4

1.2 ± 0.2

7 Days

1.1 ± 0.3

0.7 ± 0.2

0.4 ± 0.1

The highest scores for neutrophil infiltration and edema were recorded at 24 hours post-surgery, with a gradual reduction over time (Table 2). Tissue necrosis was most prominent at 24 hours but significantly decreased by 7 days.

 

Wound Healing Assessment:

Clinical evaluation of wound healing was performed at each time point, and healing efficiency was categorized as excellent, moderate, or poor based on wound size reduction, exudate levels, and granulation tissue formation.

 

Table 3: Wound Healing Scores at Different Time Points

Time Point

Excellent (%)

Moderate (%)

Poor (%)

Baseline

0

0

0

24 Hours

10

30

60

72 Hours

40

50

10

7 Days

70

25

5

By the 7th day, 70% of patients achieved excellent wound healing, while only 5% demonstrated poor healing, indicating substantial recovery over time (Table 3).

 

Statistical Analysis:

A statistically significant positive correlation was observed between higher inflammatory marker levels at 24 hours post-surgery and poor wound healing scores (p < 0.05). Furthermore, patients with lower inflammatory marker levels exhibited superior wound healing outcomes at the 7-day mark.

DISCUSSION

The present study aimed to investigate the pathological assessment of post-surgical inflammatory responses and their implications for wound healing and surgical outcomes. The findings indicate that the intensity of the inflammatory response following surgery plays a crucial role in determining the efficiency of wound healing, with elevated inflammatory markers correlating with delayed healing.

 

The acute inflammatory phase, primarily mediated by neutrophils and pro-inflammatory cytokines such as IL-6 and TNF-α, is essential for initiating the healing process by clearing debris and preventing infection (1). However, excessive inflammation can be detrimental, contributing to impaired wound healing and increasing the risk of complications (2,3). In this study, the peak levels of CRP, IL-6, and TNF-α at 24 hours post-surgery, followed by a gradual decline over the following days, align with previous findings demonstrating the rapid activation of the inflammatory cascade following tissue injury (4,5).

 

Histopathological analysis further supports the temporal pattern of inflammation, with pronounced neutrophil infiltration, edema, and necrosis observed at 24 hours. By 72 hours, macrophage infiltration becomes predominant, facilitating the transition from inflammation to tissue repair (6). This progression is consistent with earlier studies highlighting the importance of macrophages in clearing apoptotic neutrophils and promoting tissue remodeling (7,8). Additionally, the reduction of inflammatory cell infiltration and edema by day 7 suggests the resolution phase of the inflammatory response, which is critical for successful wound healing (9).

 

Elevated levels of inflammatory biomarkers, particularly IL-6 and TNF-α, have been associated with poor wound healing outcomes (10). These cytokines not only regulate local inflammatory responses but also influence systemic inflammatory pathways, potentially contributing to delayed healing in susceptible individuals (11,12). The findings of the current study are consistent with reports indicating that excessive inflammation is linked to prolonged recovery and increased incidence of post-operative complications (13).

 

Effective wound healing requires a delicate balance between pro-inflammatory and anti-inflammatory signals (14). Therapeutic strategies aimed at modulating inflammation, such as anti-inflammatory drugs, cytokine inhibitors, and immunomodulatory agents, have shown promise in improving surgical outcomes (15). Further research is needed to establish optimal therapeutic approaches to control post-surgical inflammation without compromising the body's natural defense mechanisms.

 

The study's limitations include a relatively small sample size and the focus on short-term inflammatory responses. Future studies involving larger cohorts and extended follow-up periods would provide more comprehensive insights into the relationship between inflammation and wound healing. Moreover, exploring the role of specific inflammatory mediators and their interactions may enhance our understanding of the underlying mechanisms influencing surgical recovery.

CONCLUSION

In conclusion, the findings of this study demonstrate that heightened post-surgical inflammatory responses are associated with delayed wound healing and poor clinical outcomes. Monitoring inflammatory biomarkers and employing targeted interventions to modulate inflammation may improve wound healing and enhance surgical recovery.

REFERENCES
  1. Kaner D, Soudan M, Zhao H, Gaßmann G, Schönhauser A, Friedmann A. Early Healing Events after Periodontal Surgery: Observations on Soft Tissue Healing, Microcirculation, and Wound Fluid Cytokine Levels. Int J Mol Sci. 2017 Jan 27;18(2):283. doi: 10.3390/ijms18020283. PMID: 28134829.
  2. Kuru L, Griffiths GS, Petrie A, Olsen I. Changes in transforming growth factor-beta1 in gingival crevicular fluid following periodontal surgery. J Clin Periodontol. 2004 Jul;31(7):527-33. doi: 10.1111/j.1600-051x.2004.00521.x. PMID: 15191588.
  3. Koidou VP, Cavalli N, Hagi-Pavli E, Nibali L, Donos N. Expression of inflammatory biomarkers and growth factors in gingival crevicular fluid at different healing intervals following non-surgical periodontal treatment: A systematic review. J Periodontal Res. 2020 Dec;55(6):801-809. doi: 10.1111/jre.12795. Epub 2020 Aug 25. PMID: 32840888.
  4. Villa O, Wohlfahrt JC, Koldsland OC, Brookes SJ, Lyngstadaas SP, Aass AM, Reseland JE. EMD in periodontal regenerative surgery modulates cytokine profiles: A randomized controlled clinical trial. Sci Rep. 2016 Mar 15;6:23060. doi: 10.1038/srep23060. PMID: 26976446.
  5. Okuda K, Miyazaki A, Momose M, Murata M, Nomura T, Kubota T, Wolff LF, Yoshie H. Levels of tissue inhibitor of metalloproteinases-1 and matrix metalloproteinases-1 and -8 in gingival crevicular fluid following treatment with enamel matrix derivative (EMDOGAIN). J Periodontal Res. 2001 Oct;36(5):309-16. doi: 10.1034/j.1600-0765.2001.360506.x. PMID: 11585118.
  6. Emecen-Huja P, Eubank TD, Shapiro V, Yildiz V, Tatakis DN, Leblebicioglu B. Peri-implant versus periodontal wound healing. J Clin Periodontol. 2013 Aug;40(8):816-24. doi: 10.1111/jcpe.12127. Epub 2013 Jun 18. PMID: 23772674.
  7. Kuru L, Kirby AC, Griffiths GS, Petrie A, Olsen I. Changes in soluble adhesion molecules in gingival crevicular fluid following periodontal surgery. J Periodontol. 2005 Apr;76(4):526-33. doi: 10.1902/jop.2005.76.4.526. PMID: 15857092.
  8. Pontoriero R, Carnevale G. Surgical crown lengthening: a 12-month clinical wound healing study. J Periodontol. 2001 Jul;72(7):841-8. doi: 10.1902/jop.2001.72.7.841. PMID: 11495130.
  9. Kaner D, Zhao H, Terheyden H, Friedmann A. Improvement of microcirculation and wound healing in vertical ridge augmentation after pre-treatment with self-inflating soft tissue expanders - a randomized study in dogs. Clin Oral Implants Res. 2015 Jun;26(6):720-4. doi: 10.1111/clr.12377. Epub 2014 Apr 16. PMID: 24735431.
  10. Gamonal J, Acevedo A, Bascones A, Jorge O, Silva A. Levels of interleukin-1 beta, -8, and -10 and RANTES in gingival crevicular fluid and cell populations in adult periodontitis patients and the effect of periodontal treatment. J Periodontol. 2000 Oct;71(10):1535-45. doi: 10.1902/jop.2000.71.10.1535. PMID: 11063385.
  11. Keles GC, Cetinkaya BO, Isildak I, Koprulu H, Acikgoz G. Levels of platelet activating factor in gingival crevice fluid following periodontal surgical therapy. J Periodontal Res. 2006 Dec;41(6):513-8. doi: 10.1111/j.1600-0765.2006.00898.x. PMID: 17076775.
  12. Dellavia C, Canciani E, Rasperini G, Pagni G, Malvezzi M, Pellegrini G. CEMP-1 Levels in Periodontal Wound Fluid during the Early Phase of Healing: Prospective Clinical Trial. Mediators Inflamm. 2019 Feb 24;2019:1737306. doi: 10.1155/2019/1737306. PMID: 30918466.
  13. Javed F, Al-Daghri NM, Wang HL, Wang CY, Al-Hezaimi K. Short-term effects of non-surgical periodontal treatment on the gingival crevicular fluid cytokine profiles in sites with induced periodontal defects: a study on dogs with and without streptozotocin-induced diabetes. J Periodontol. 2014 Nov;85(11):1589-95. doi: 10.1902/jop.2014.140150. PMID: 24835413.
  14. Leblebicioglu B, Alssum L, Eubank TD, Yildiz VO, Tatakis DN. Wound Fluid Cytokine Profile Following Bone Regeneration Procedures. J Oral Implantol. 2020 Apr 1;46(2):107-113. doi: 10.1563/aaid-joi-D-19-00061. PMID: 31909694.
  15. Penova-Veselinovic B, Keelan JA, Wang CA, Newnham JP, Pennell CE. Changes in inflammatory mediators in gingival crevicular fluid following periodontal disease treatment in pregnancy: relationship to adverse pregnancy outcome. J Reprod Immunol. 2015 Nov;112:1-10. doi: 10.1016/j.jri.2015.05.002. PMID: 26093363.
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