4 DISCUSSION
In elderly individuals, rebound sensitivity decreases due to atrophy of
the abdominal muscles, along with increased pain threshold due to
conduction differences in the nervous system and certain changes in the
detection and limitation of pain. Hence, the clinical picture tends to
be atypical and obscure in the elderly [11]. The time from the onset
of symptoms to hospital admission and surgery also seems higher in the
elderly [12,13]. Delayed admission leads to perforation of the
appendix. Acute appendicitis perforation is observed in 18-34% of the
general population [6]. However, this rate increases up to 41-56.3%
in geriatric patients [2,3,9]. Male sex, anorexia, fever
≥38∘C, and duration of pain before admission are risk
factors for perforated appendicitis. The most important factor remains
delayed admission to hospital [3,6]. Male patients are observed to
be more reluctant for admission to hospital and therefore present later
[14]. In the current study, the rate of complicated appendicitis was
found as 34.27%, somewhat below the data in the literature. Time to
hospital admission remains the most important factor for perforation,
with a mean of 3.3 days for complicated appendicitis patient group.
Gender plays no role as a factor in the occurrence of complicated
appendicitis.
Comorbid diseases tend to increase morbidity and mortality, although
they have not been identified as a significant factor for perforation
[3]. For elderly patients, the rate of comorbid disease is observed
to be 43-60.7% [3,6]. The rate of comorbid disease in our sample
was higher than the reports in the literature (69.9%), with no
significant difference between the groups, suggesting that it is not a
risk factor for complicated appendicitis.
There is no clinical symptom, finding, laboratory test, or radiological
method to diagnose acute appendicitis alone. Despite all advancements,
it may still prove difficult to diagnose AA. This proves even more
complicated in geriatric patients [15]. Advanced radiological
imaging methods facilitate diagnosis. However, particularly in rural
regions, surgeons may not have easy access to such advanced imaging
methods [10]. Thus, studies have focused on easily accessible and
cost-efficient markers with a high diagnostic value [1,9]. Surgeons
have been interested in simple laboratory markers that can help diagnose
AA and determine perforation status [16]. Complete blood count (CBC)
is an ideal marker for these properties. It can be easily accessed and
quickly evaluated in many healthcare institutions, particularly in
emergency rooms [10].
White blood cell (WBC) count is the most commonly used laboratory
parameter for diagnosing AA. WBC count often increases in acute
appendicitis patients, but it is not a specific marker because it can
also increase in many other diseases [16]. One study reports that
WBC has a cut-off value of 10.6, AUC: 0.66, a sensitivity of 71.2%, and
a specificity of 68.2% for determining perforation in the elderly
[9]. Here, WBC count was found to be a marker with high sensitivity
and low specificity for diagnosing AA (Cut-off value:8.97, AUC:0.72,
sensitivity 85%, specificity 57%). However, it was not found to be a
biomarker with high diagnostic value for determining complicated
appendicitis.
As the degree of inflammation increases, the neutrophil level increases
and the relative lymphocyte count decreases. Hence, the neutrophil to
lymphocyte ratio (NLR) increases [17]. NLR has been used as a
biomarker for morbidity, mortality, and survival in many disorders,
including inflammatory and neoplastic diseases [16,18]. NLR has been
demonstrated to be superior to other traditional infection markers like
WBC, neutrophil, and CRP for determining AA severity [9,19]. Here,
neutrophil and NLR levels were determined to be biomarkers for
diagnosing AA with similar diagnostic values, while only NLR was a
significant biomarker for determining complicated appendicitis.
MPV is part of routine CBC tests. It is a marker for platelet size and
function. MPV has been examined for its diagnostic and prognostic values
in a number of inflammatory diseases and appendicitis [20]. However,
there are conflicting findings in the literature, some showing increased
MPV in AA patients [21], while others showing decreased MPV
[20,22]. Similar to the literature, we obtained conflicting results
on MPV. MPV was the highest in the complicated appendicitis group. While
MPV was expected to be the lowest in the negative appendectomy group, it
was the lowest in the uncomplicated appendicitis group. Despite the
conflicting findings, MPV was determined as a marker with the highest
diagnostic value for appendicitis.
PLR is another inflammatory marker that can easily be obtained during
simple hemogram tests. In many cancers and inflammatory events, the
release of proinflammatory cytokines causes proliferation of
megakaryocytes. Also, platelets are known to affect infections.
Therefore, PLR levels can be used for diagnosing appendicitis [23].
Yıldırım et al. found PLR to be a useful marker for differentiating
between complicated and uncomplicated appendicitis (cut-off value:
169.7, sensitivity: 74.4%, specificity: 73.5%) [24]. Our findings
revealed that PLR was an important marker for differentiating between
complicated and uncomplicated appendicitis. Although it was found to
have the lowest sensitivity, it had the highest specificity (Cut off
value:190.6, AUC:0.64, sensitivity 50%, specificity 82%).
RDW (red cell distribution width) is a subparameter that demonstrates
the distribution volume of circulating erythrocytes. Inflammation
disrupts blood cell maturation, damaging red cell membrane and leading
to increased RDW [22]. RDW has been shown to increase significantly
in complicated appendicitis, but its diagnostic values have not been
specified [25]. Comparing those with appendicitis and those without,
no significant difference has been found [22,25]. Similarly, in the
current study, RDW was found to be a marker for differentiating between
complicated and uncomplicated appendicitis with a high diagnostic value,
but not a significant marker for diagnosing AA. (Cut off value:13.15,
AUC:0.63, sensitivity 69%, specificity 60%).
In systemic infection cases, some bacteria, particularly E. coli, cause
hemolysis and endotoxemia. Endotoxemia and bacteria result in impaired
bilirubin excretion from the bile canaliculi. This leads to increased
bilirubin levels in the blood [26]. It is well known that bilirubin
levels increase in AA. Direct and total bilirubin levels increase in
acute and complex appendicitis and are used as a diagnostic marker
[27]. Despite limited in number, research has shown
hyperbilirubinemia to be a biomarker for predicting perforation in
geriatric patients [9]. Here, both direct bilirubin and total
bilirubin levels were found to be important biomarkers for diagnosing
acute appendicitis and predicting complications. Also, they were the
markers with the highest specificity for predicting AA status.
The most frequently used serological indicators for diagnosing acute
appendicitis are leukocyte counts and C-reactive protein (CRP) levels.
CRP is an acute-phase reactant that is synthesized in the liver in
response to infection or inflammation [28]. Jung et al. found CRP as
a marker for determining perforation in geriatric patients with a high
diagnostic value and a cut-off value of 2.09/mg/dl [9]. Another
research emphasized its high diagnostic value for determining
perforation in elderly patients (AUC: 0.811 with a cut-off value of
10.19 mg/dl) [29].
The most recent SIFIPAC/WSES/SICG/SIMEU guidelines recommend the use of
CRP and leukocyte levels together for diagnosing AA in the elderly
[30].
In determining perforation, CRP and TB are noted to be significant
markers with high diagnostic value when used together [31]. In the
present study, CRP was found to be an important marker for diagnosing
acute appendicitis and determining complication status. Again, similar
to the findings in the literature, TB and CRP were found to increase in
parallel to each other (complicated appendicitis: Cut off value:5.11,
AUC:0.83, sensitivity 72%, specificity 76%).
To the best of our knowledge, this is the first study in the literature
to demonstrate the diagnostic efficiency of MPV, PLR, and RDW for
determining acute appendicitis severity in the elderly. We can define
these biomarkers as new diagnostic markers for geriatric age patients.
USG and CT are some of the basic imaging modalities that are most
commonly used for diagnosing AA and determining complications. Yet,
these imaging methods can be difficult to access, leading to further
problems. CT has certain disadvantages, such as high costs, ionizing
radiation, and contrast agent reactions. USG, on the other hand, has
significant disadvantages such as being dependent on the person
performing it and that it cannot be retrospectively examined
[32,33]. Also, CT has a lower sensitivity in the elderly compared to
the general population [34]. CT has been reported to have a low
sensitivity for detecting perforated appendicitis without abscess or
phlegm [35]. In the current study, we found CT to have a sensitivity
of 77.7% and a specificity of 70%, while USG had a sensitivity of
74.2% and a specificity of 18.2%. USG has a particularly low
specificity.
It is worth mentioning that the length of hospital stay was higher in
the elderly compared to younger patients. Higher complication rates,
prolonged antibiotic treatments, and other comorbid diseases may be
associated with this finding [36]. Omari et al. found a mean length
of hospital stay of 4.2 days for uncomplicated appendicitis patients and
7.4 days for complicated appendicitis patients [3]. In our patients,
as expected, the longest length of stay was observed in the complicated
appendicitis group, while the shortest length of stay was observed in
the negative appendectomy group. With a descending order, length of
hospital stay was 6.59, 3.34, and 3.13 days in our groups.
Prognosis for uncomplicated appendicitis is almost similar between young
and elderly patients. However, in the case of perforation, morbidity and
mortality increase dramatically in the elderly [8,29]. Elderly
appendicitis patients have a postoperative complication rate of 21-60%
and a mortality rate of 0.97-3% [3,6,7]. In our study, the rate of
postoperative complications was 35.7%, with no mortality. The rate of
complications was found to be higher in the perforated patient group.
The low mortality and morbidity rates in our findings can be explained
by the low number of perforated appendicitis cases.
The major limitation of our study is that it is a retrospective study.
Another limitation is a lack of analysis of symptoms and physical
examination findings, which are crucial for diagnosing AA. Still, our
research had certain strengths, including the high number of patients
compared to most studies in the literature, the analyses of many
biomarkers and obtaining new data, and providing more information by
dividing the patients into three groups.