An Evaluated Preoperative C-Reactive Protein Level as a Predictor of Difficult Laparoscopic Appendectomy

By Sana Shahid¹, Erum Kazim², Bushra Kiran Naeem², Lamia Batool Rizvi³, Raheel Ahmed², Syed Muhammad Hamza⁴

Affiliations

1. Department of Surgery, Kutiyana Memon Hospital, Karachi, Pakistan
2. Department of General Surgery, Dr. Ruth, K. M. Pfau Civil Hospital, Dow University of Health Sciences, Karachi, Pakistan
3. Department of Surgery, Ziauddin Hospital, Karachi, Pakistan
4. Department of Surgery, Combined Military Hospital, Karachi, Pakistan

doi: 10.29271/jcpsp.2025.12.1526

ABSTRACT
Objective: To determine the diagnostic accuracy of elevated preoperative C-reactive protein (CRP) level in predicting a difficult laparo- scopic appendectomy (LA).
Study Design: A descriptive study.
Place and Duration of the Study: Department of General Surgery, Dr Ruth, K. M. Pfau Civil Hospital, Dow University of Health Sciences, Karachi, Pakistan, from June to November 2021.
Methodology: Patients operated for LA underwent baseline investigations and preliminary anaesthesia fitness. Intraoperative findings, including difficult dissection due to dense adhesions, were recorded by a primary surgeon on postoperative notes. Serum CRP level, specificity, sensitivity, diagnostic accuracy, positive predictive value (PPV), and negative predictive value (NPV) were measured. ROC curve was plotted, and the area under the curve (AUC) was utilised. An independent-sample t-test was used to compare mean CRP in patients who underwent laparoscopy-corrected-to-open appendectomy with those who underwent LA. The Chi-square test was used to compare the differences in the proportion of conversion to open surgery from LA and between CRP levels (<220 vs. ≥220 mg/L).
Results: The mean age of the 181 patients was 39.21 ± 10.90 years. There were 87 (48.07%) males and 94 (51.93%) females. The cut-off CRP levels were 220 mg/L for predicting conversion to open appendectomy from LA. The percentages of PPV, NPV, accuracy, sensitivity, and specificity of CRP ≥220 mg/L were 86.96%, 93.26%, 93.02%, 87.37%, and 90.01%, respectively. The area under the receiver operating characteristic curve (AUROC) for the said study model was 0.941, with 95% confidence interval of 0.91 to 0.97.
Conclusion: Elevated preoperative CRP level is a significant predictor of difficult LA. The CRP level aids in selecting patients for early discharge and reducing unnecessary investigations.

Key Words: Appendicitis, Laparoscopic appendectomy, C-reactive protein level.

INTRODUCTION

Acute  appendicitis  is  one  of  the  most  frequent  emergency admissions in surgical departments. Its incidence has been reported as 8.6% in adult males and 6.7% in females, with an increased incidence in younger age groups.¹ Diagnostic laparo- scopy with appendicectomy (LA) has become an accepted method for both the investigation and treatment of appendicitis.²

To streamline the diagnosis, several clinical scoring systems and imaging modalities have been utilised, assigning numerical values  based  o n underlying   pathological findings.³      

This is followed by the categorisation of the disease into two distinct stages—simple and complex—based on clinical assessment and the analysis of certain laboratory parameters. This distinction, although often difficult, is important in determining the timing of surgical intervention, the type of procedure, the subsequent length of hospital stay, and the overall outcome. The interpretation of certain laboratory red flags can be utilised to differentiate early from advanced complicated stages of acute appendicitis. Later, this can be followed by laparoscopy, provided the availability of skilled surgeons. This approach allows clinicians to confirm and treat the patients simultaneously when the diagnosis has been established based on  laboratory  evaluation  or  imaging.³

Being a prevalent surgical emergency, the frequency of acute appendicitis is 7% in the population, and it often develops between the ages of 10 and 30 years. Minimally invasive laparo- scopic appendectomy (LA), along with diagnostic laparoscopy, is the accepted procedure for both investigation and treatment. However, concerns remain in cases of difficult or compli-cated appendicitis, where an experienced surgeon must know the limitations of the surgery and determine when to convert to laparoscopic converted-to-open appendectomy (LCOA) to prevent further complications. When contamination, unexpected complications, or technically demanding situations occur (e.g., a difficult retrocaecal appendix or an appendicular abscess), conversion becomes necessary. Therefore, the conversion rate largely depends on these surgical findings.³

C-reactive protein (CRP) is an acute phase reactant protein produced by the liver after the release of pro-inflammatory cytokines, importantly interleukin-6, during tissue infarction, trauma, inflammation, infection, and malignancy.⁴ It serves as an excellent indicator of the intensity of inflammation, as its blood concentration is determined by its production, contemplating the severity of its pathological course. The specificity and sensitivity of CRP are 70.27% and 88.21%, respectively.³

Goel et al. reported a conversion rate of 13% from LA to LCOA.⁵ They identified predictors of difficult LA, including age of >60 years, a history of previous exploratory laparotomy with a lower midline incision, delayed presentation (>24 hours), and the presence of peri-appendicular collection in acute appendicitis. Furthermore, Hellberg et al. reported a conversion rate of 12%.⁶ A study from 2017 has concluded that there is an increased likelihood of conversion from LA to LCOA with a higher value of CRP. They also have reported that a preoperative CRP level of >100 mg/L is a statistically major predictor of LCOA.⁷ Shelton et al. reported a CRP level of >150 mg/L as a sovereign predictor of difficult outcome.² Along with Shelton, many other authors have also reported that there is established inflammation with a CRP level higher than 150 mg/L, which indicates superior complication rates, making the surgery technically demanding.^2,8-11 This study aimed to investigate the relationship between a preoperative CRP level and the difficulty of LA. Specifically, it sought to determine whether an elevated CRP level can predict a difficult procedure.

METHODOLOGY

This analytical study was conducted at the Department of General Surgery, Dr Ruth K. M. Pfau Civil Hospital, Dow University of Health Sciences, Karachi, Pakistan, from June to November 2021. The sample size was calculated using the SS calculator for sensitivity and specificity. Statistical assumptions included a 5% alpha error and a 95% confidence interval. The estimated prevalence of difficult laparoscopic surgery was 22.2%, with a sensitivity of 88.21% and a specificity of 70.27%. The sample size contained 181 patients for this study. The sampling technique was a non-probability consecutive sampling. Inclusion criteria included patients aged >18 years, with an upper range of 60 years, to undergo LA. Exclusion criteria included BMI >35 kg/m², previous abdominal surgery, American Society of Anesthesiologists (ASA) class 4 or 5, and refusal  to  provide  informed  consent.

After obtaining approval from the Institutional Review Board of Dow University of Health Sciences, Karachi, Pakistan (Approval No: IRB-1895/DUHS/Approval/2021/320; dated: January 30, 2021), 181 consecutive patients of acute appendicitis visiting the Hospital Surgical Emergency Department and meeting the inclusion and exclusion criteria were included. Informed consent was obtained from all patients, and the study details were fully explained to each patient. All subjects underwent baseline investigations and preliminary anaesthesia assessment prior to LA. In addition, serum CRP levels were measured preoperatively for each patient in the surgical assessment bay. Only final-year surgical residents performed the operations under the direct supervision of the senior registrar and on-call fellow, while the junior residents were not involved in the procedures.

Demographic details, such as age and gender, were recorded for all patients. Intraoperative findings were recorded in the postoperative notes by the primary surgeon, with particular emphasis on difficult dissection (such as adhesions between the appendix, momentum, small bowel and caecum, amalgamated with surrounding structures, or the presence of a perforated and gangrenous appendix) in case of dense adhesions. Other variables, such as duration of symptoms, BMI (kg/m²), baseline investigations, preoperative CRP levels, difficult dissection (yes/no), time of the surgery (measured from incision to closure), and conversion to open appendectomy, were documented in an already designed proforma.

The data were statistically analysed using SPSS version 19 and Stata/SE 14.2 for Windows. Continuous data such as age, duration of symptoms, and preoperative CRP were presented as mean ± standard deviations (SD), while qualitative data such as gender, comorbidities (hypertension (HTN), diabetes mellitus (DM), known duration of at least 1 year or on medications), elevated CRP, and difficult laparoscopies, were presented as frequencies and percentages. Two-by-two tables were used to calculate sensitivity, specificity, diagnostic accuracy, positive predictive value (PPV), and negative predictive value (NPV). The ROC curve was plotted, and the area under the curve (AUC) was used to determine the diagnostic accuracy of CRP levels. The cut-off was determined based on high sensitivity (86.96%) and low 1-specificity (93.26%) obtained from the ROC curve. An independent-sample t-test was used to compare mean CRP values between patients who underwent LCOA and those who underwent LA. The Chi-square test was used to compare the differences in the proportion of conversion to open surgery from LA to LCOA, and between CRP levels (< 220 vs. ≥220 mg/L).

Table   I:   Descriptive   statistics   of  the   patients.

Variables	Mean	SD	Minimum	Maximum
Age (years)	39.21	10.90	18	59
Duration of symptoms (days)	4.69	2.25	1	10
Serum CRP (mg/L)	165.07	99.43	7	357
Duration of procedure (hours)	1.60	0.66	1	3
CRP: C-reactive protein.

Table II: Sensitivity, specificity, PPV, and NPV for different cut-off points for CRP in predicting conversion from LA to open surgery.

Frequencies
Cut-off points for CRP mg/L	True positive	True negative	False positive	False negative	Total
150	80	71	18	12	181
180	80	74	15	12	181
220	80	83	6	12	181**
225	63	86	3	29	181
Percentages
Cut-off points for CRP mg/L	Sensitivities	Specificities	PPV	NPV	Accuracies
150	86.96%	79.79%	81.63%	85.54%	83.42
180	86.96%	83.15%	84.21%	86.05%	85.08
220*	86.96%	93.26%	93.02%	87.37%	90.01
225	68.48%	96.63%	95.45%	74.78%	82.32
CRP: C-reactive protein; PPV: Positive predictive value; NPV: Negative predictive value; LA: Laparoscopic appendectomy. *CRP equal to and above 220 mg/L is the best cut-off value, in which high sensitivity and specificity, as well as diagnostic accuracy, were high; **A p-value was obtained by the Chi-square test (p <0.001).

Figure 1: Receiver operating characteristic (ROC) curve for the CRP, with 95% confidence interval.
 

RESULTS

A total of 181 patients who underwent LA were included in the present study. The mean age of the patients was 39.21 ± 10.90 years. There were 87 (48.07%) males and 94 (51.93%) females. Age, mean serum CRP, duration of symptoms, and duration of the procedure are presented in Table I. Out of the 181 cases, 31 (17.7%) were diabetic and 48 (26.5%) were hypertensive. The conversion rate from LA to LCOA was 50.83% (92/181). The mean CRP level was considerably higher in patients who required conversion compared to those who did not (238.315 ± 57.45 vs. 89.34 ± 7.79 mg/L; p = 0.0001).

The fluctuating levels of CRP and their association with conversion from LA to LCOA are shown in Table II. Among the 95 patients, 12 (12.63%) underwent conversion, who were labelled as CRP level <220 mg/L. In contrast, out of 86 patients, 80 (93.02%) were converted to open surgery, labelled as having a CRP level ≥220 mg/L (p <0.001). The PPV, NPV, diagnostic accuracy, specificity, and sensitivity for CRP ≥220 mg/L were 86.96%, 93.26%, 93.02%, 87.37%, and 90.01%, respectively.

The area under the receiver operating characteristic curve (AUROC) for the study model was 0.941, with a 95% confidence interval of 0.91 to 0.97, as shown in Figure 1. Stratification analysis was performed, and the most accurate cut-off point for CRP was found to be 220 mg/L for all stratified groups. There was no significant difference in AUROC between the stratified groups, and the diagnostic accuracy and AUC values were >85%.

DISCUSSION

Minimally invasive laparoscopic procedure is the ideal approach for most abdominal surgeries because it offers less pain, better surgical outcomes, and shorter hospital stay compared with conventional open surgery. Earlier studies have reported LCOA rates ranging from 0–17%, while some papers have identified independent risk factors for LCOA, including male gender, age, decreased white blood cell (WBC) count, obesity, raised CRP, diabetes, base necrosis, and appendicitis complicated by peritonitis and abscess.^12-16 Additional operative time and increased medical costs are associated with LCOA. Moreover, as clearly illustrated in this study, LCOA negates the advantages of minimally invasive procedures, including reduced wound infections, less pain, and lower hospital stay costs. Therefore, there should be pre-surgical criteria for evaluating risk factors, based on which the operating surgeon can decide the most suitable surgical approach for each individual, ensuring maximum benefit in all reports.

The present study showed 39.21 ± 10.90 years as the mean age. Out of 181 patients, 48.07% were males and 51.93% were females. The rate of conversion from LA to LCOA was 50.83%. In Ebied et al.’s study, 60 (60%) patients were males and 40 (40%) were females, and the mean age was 20–55 years.¹⁷ In Shelton et al.’s study, the mean age was 32 years, 57% of patients were males, and 83% patients underwent LA and 17% LCOA.²

C-reactive protein is an inexpensive, easily available, and regular routine investigation. Numerous studies highlighted its usefulness and accuracy as a diagnostic tool for acute appendicitis.¹⁸ In the present study, ninety-five patients had a low CRP level of <220 mg/L; of which, 12.63% underwent LCOA. In contrast, 86 patients had a high CRP level of ≥220 mg/L; of which, 93.02% underwent LCOA (p <0.001). Shimoda et al. also reported a considerably high CRP of >99 mg/L, which is also considered a sovereign indicator in the conversion rates,¹⁹ consistent with the findings of Shelton et al.² These studies indicate that preoperative CRP levels of >100 and >150 mg/L were statistically considerable predictors of conversion from LA to LCOA. C-reactive protein (CRP) increases in response to inflammatory conditions, and its increased values indicate more intense acute appendicitis, associated with complications and severe local inflammation. Shelton et al. identified a CRP level of >150 mg/L as a high and self-sufficient factor for predicting severe complications in acute appendicitis.² Geol et al. provided strong evidence that CRP levels of >150 mg/L indicate established inflammation, a higher complication rate, and increased technical difficulty during surgery.⁵

Several studies reported that the sensitivity of CRP was higher than WBC count in the diagnosis of simple acute appendicitis.²⁰ In the present study, the diagnostic accuracy, specificity, and sensitivity of CRP ≥220 mg/L are 90.01%, 93.26%, and 86.96%, respectively. In the study by Ebied et al., sensitivity was 93.3% and specificity was 86.6%,¹⁷ consistent with the findings of Sammalkorpi et al. and Erkasap et al.,^21,22 Asfar et al. showed a higher specificity and a lower sensitivity of the CRP level.²³ It is an excellent indicator of the intensity of inflammation, as its concentration in blood is determined by its production, contemplating the severity of its pathological course. The specificity and sensitivity of CRP are 70.27% and 88.21%, respectively.² It has been noted that both WBC count and CRP level in cases of simple acute appendicitis demonstrate increased PPV, indicating their high diagnostic utility. This study is showing results similar to another study, which shows that these biomarkers are effective indicators of both acute and perforated appendicitis.²⁴ Beltran et al. confirmed the elevated specificity of both in cases of perforated appendix.²⁵

Raised CRP indicates a severe inflammatory process, leading to even intense acute appendicitis. It is believed that these higher levels are secondary to the infective or inflammatory mechanism, as well as complications such as appendicular abscess or perforated appendix. Patients with high CRP levels should undergo abdominal CT in order to rule out perforated and gangrenous appendices. Elevated CRP levels is associated with increased postoperative complications and morbidity in various surgical populations.² However, the relationship between CRP levels and surgical difficulty is more complex, and further research is needed to fully understand its implications.³ This study shows that high CRP levels not only make the surgery technically more difficult but also escalate the possibility of complications in the LA patients.

There were certain limitations. First, the study was conducted at a single institution. Second, as surgeries were performed by multiple surgeons, the conversion threshold depended on individual judgement and laparoscopic skills, introducing a potential bias. Third, the sample size was small, limiting the generalisability of the findings.

CONCLUSION

Elevated preoperative CRP levels (>220 mg/L) is a significant predictor of difficult LA. The level of CRP can identify high-risk patients, aiding surgical planning, and reducing complications. These findings highlight the value of biomarkers in improving preoperative assessment and outcomes.

ETHICAL APPROVAL:
Ethical approval was obtained from the Institutional Review Board of Dow University of Health Sciences, Karachi, Pakistan. (Approval No: IRB-1895/DUHS/Approval/2021/320; dated: January 30, 2021).

PATIENTS’ CONSENT:
Written informed consent was taken from all the patients, and the details regarding the study were explained to each one of them.

COMPETING INTEREST:
The authors declared no conflict of interest.

AUTHORS’ CONTRIBUTION:
SS: Conception and design of the study.
EK: Data analysis, drafting, and proofreading.
BKN: Manuscript writing, data analysis, and data interpretation.
LB, SMH: Data collection.
RA: Writing introduction and literature search.
All authors approved the final version of the manuscript to be published.
 

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