DISCUSSION
Our study is the first study evaluating the role of serum markers in the
early detection of AL after gyne-oncological operations. There have been
many studies showing the possible role of serum PCT and CRP in the
diagnosis of AL after elective colorectal surgeries6.
In the study of Alvara Garcia-Granero et al., in case of major AL, PCT
and CRP were proved as reliable predictors on POD 3 to 5 with the best
value for PCT on POD 5 was 0.31 ng/ml (AUC = 0.86) (Sensitivity = 100%,
specifity = 72%, positive predictive value = 17%, negative predictive
value = 100%) 7. Also, in a recent meta-analysis, it
was concluded that PCT is a useful negative test for AL after elective
colorectal surgery with negative predictive values ranging from 95% to
100% (highest AUROC was 0.88 on POD 5). But, as an isolated test, poor
positive predictive values of up to 34%, limit its use in predicting
AL8. Different from elective colorectal surgeries, in
the surgical concept of gynecological malignancies (especially in
advanced ovarian cancer), debulking procedures including both upper and
lower abdomen and peritonectomy were needed to reach zero macroscopic
residual disease to get overall survival
advantage9,10. So, we wanted to analyze these markers
whether they were also beneficial in the early diagnosis of AL after
gyne-oncological surgeries. And, a statistically significant difference
was found between the albumin values on POD 3 (p=0.028), on POD 4
(p=0.045) and the platelet values on POD 1 (p<0.001).
Pre-operative hypoalbuminemia is a well-known risk factor for AL, but
few studies evaluated the role of peri-operative albumin on AL after
intestinal surgeries11,12. In the study of Shimura et
al., it was shown that lower average levels of serum albumin on POD 1
and POD 3 (HR = 4.49, 95% CI = 0.77–29.58; p = 0.0955) and
higher average levels of serum leukocytes on POD 1 and POD 3 (HR = 5.62,
95% CI = 0.76–115.34; p = 0.0952) were independent risk factors
for AL11. Similarly, in our study, lower levels of
albumin on POD 3 and 4 were associated with AL. In the study of
Margarson et al., after giving intravenous hypertonic albumin solution,
serum albumin concentrations decrease significantly faster in septic
patients than in healthy controls and that was explained by increased
vascular leak of the albumin13. But, it is unclear
whether hypoalbuminemia is the cause or result of the AL.
Interestingly, in our study, it was shown for the first time in the
literature that platelet count was associated with AL as the mean
platelet values were lower on POD 1 in the AL group. In the study of
Dewitte et al, possible mechanisms of blood platelets in sepsis
pathophysiology were reviewed14. According to this,
beyond their roles in haemostasis, platelets are now accepted as active
actors of immune respone playing role in host defence and tissue
integrity. This interesting relation of low platelets with AL found in
our study should be further evaluated in prospective trials.
Although it was not statistically significant (p>0.05), in
our study, median PCT values on POD 8 to 10 were higher in the AL group.
And, PCT values increased later compared to other studies in the
literature7,15. Intraabdominal sepsis may have delayed
in patients with AL due to our local peroperative guideline which was
different from ERAS protocol16. Most likely reason for
this late increase of PCT in patients with AL may be antibiotic
supression during our hospitalization period. In accord to this, Charles
et al. showed that empirical antibiotic therapy was associated with a
greater decline in PCT following the onset of sepsis between day 2 and
317.
In contrast to previous studies, we could not find a statistically
significance between AL and postoperative CRP
levels7,18. In a systematic review made by Singh et
al., it was shown that serum CRP level on POD 3, 4, and 5 had comparable
diagnostic accuracy for the prediction of AL with a AUROC of 0.81, 0.80,
and 0.80, respectively18. The derived CRP cut-off
values were 172 mg/L on POD 3, 124 mg/L on POD 4 and 144 mg/L on POD 5.
And these corresponded to a negative predictive value of 97% and a
positive predictive value of 21-23% 18. In the study
of Smith et al., for the first time in the literature, an association of
biomarker trajectory was assessed, instead of isolated daily values. And
the trend of CRP for the first 5 days following surgery, appeared to be
highly accurate for diagnosing AL, with a daily rise of 50 units had a
sensitivity of 91% and a negative predictive value of
99.3%19. Our results showed that PCT and CRP did not
work to predict AL before clinical onset of sepsis in patients operated
for gyne-oncological surgeries. After ROC analysis, the best cutt-off
point for PCT was determined to be 0.11 ng/mL on POD 9. Although this
statistical value was not useful for the early clinical management, it
could be used in patients who had vague symptoms and indeterminate
radiologic imaging. Our low number of positive cases (5 cases of AL) may
have prevented us from observing possible effect of PCT and CRP on the
early days of leakage.
Our study had some limitations. First, the study had retrospective
nature comprising consecutive patients managed on the basis of local
clinical guideline. Second, patient cohort included heteregoneus type of
malignancies and surgeries. On the other hand, PCT, previously shown to
predict AL in colorectal surgery, has been shown for the first time to
be useless in gynecological oncology. Also, different from literature,
the increase of PCT seen in AL appeared very soon that should be
supported with further studies.
In conclusion, serum PCT and CRP concentrations were not found to be
helpfull for the early diagnosis of AL in patients operated for
gyne-oncological malignancies. Low levels of albumin and platelets in
the first days after the operation may be clue for a possible AL.