Preoperative Neutrophil Lymphocyte Ratio in Prediction of Adnexal Mass Torsion

Aims Adnexal torsion commonly affects reproductive age group females. Prompt diagnosis and early management help in the preservation of fertility. However, its diagnosis is challenging. Preoperative diagnosis can be suspected in only 23–66% of the cases and half of the patients operated for adnexal torsion have different diagnosis. This article thus aims to identify the diagnostic value of preoperative neutrophil lymphocyte ratio in adnexal torsion in comparison with other untwisted unruptured ovarian cysts. Methods This was a retrospective study conducted in the duration of five years from 1st January 2016 to 1st January 2020. The data about demographic parameters, hematological parameters, operative approach, operative technique, and histopathological reports were derived from an electronic database and documented on proforma. SPSS was used for statistical analysis. Logistic regression analysis and influence of each factor on preoperative diagnosis of Adnexal torsion was evaluated. Results A total of 125 patients were included in the article (adnexal torsion group n = 25, untwisted unruptured ovarian cyst group n = 100). There was no statistically significant difference in comparison to age, parity, and abortion between both groups. Most patients had undergone laparoscopic surgery which was based on surgeon's skill and preference. Nineteen (78%) patients in the adnexal torsion group underwent oophorectomy while infarcted ovary was seen in only 4 cases. Among the blood parameters, only neutrophil-lymphocyte ratio (NLR) >3 was found to be statistically significant under logistic regression analysis. Most common adnexal pathology to undergo torsion was serous cyst. Conclusion Preoperative neutrophil-lymphocyte ratio can be a predictive marker for diagnosis of adnexal torsion and can differentiate it from untwisted unruptured ovarian cysts.


Introduction
Adnexal torsion is the twisting of the vascular pedicle of an ovary, an ovary with cyst, a fallopian tube, or a paratubal cyst. It results in ischemia of the structure distal to twisting with an acute onset of pain [1]. It accounts for 2.7% to 7.4% gynecological emergencies [2]. Te most common age group afected is reproductive age group [3]. Early diagnosis and management of adnexal torsion helps in preservation of fertility; however, its diagnosis is challenging. With detailed history, clinical examination and pelvic ultrasound preoperative diagnosis can be suspected in only 23-66% of the cases and half of the patients operated for adnexal torsion have diferent diagnosis [4].
In adnexal torsion, ischemia followed by reperfusion causes accumulation of activated neutrophils. Tis in turn releases reactive oxygen species (ROS) which leads to an increase in infammatory parameters such as white blood cell (WBC) count, neutrophils, and neutrophil-lymphocyte ratio (NLR) [5]. Adnexal torsion is associated with high infammatory burden [6]. Elevated NLR is a characteristic of infammatory conditions shown in various studies. For thyroid disorders, NLR of the subjects with increased uptake in thyroid uptake scintigraphy was signifcantly higher than those with normal uptake [7]. In the irritable bowel syndrome (IBS) group, NLR > 2.2 was found to be predictive of disease than normal population [8]. Patients with NLR ≥ 2.4 were 20.5 times more likely to have COVID-19 compared to patients whose NLR was ≤2.4 [9]. Similarly, the median NLRs of patients with infammatory bowel disease presenting with abscesses were signifcantly higher than in patients without the disease. Moreover, higher ratio suggested acute indication for surgery [10]. For those with uncontrolled diabetes, median NLR of the type 2 DM group >2.4 was found to be signifcant [11]. Also, patients who had atrial fbrillation with the history of diabetes had higher NLR ratio than patients with atrial fbrillation without diabetes [12]. Tyroiditis patients when assessed also had high NLR of more than 2.1 compared to normal population [13]. Tese fndings of various infammatory conditions over the decades have showed the importance of elevated NLR in supporting the diagnosis. Same mechanism could be correlated with adnexal torsion. Along with clinical and radiological fndings, if hematological parameters can provide additive beneft in the diagnosis of adnexal torsion, then we can be more accurate and plan the management accordingly. However, there is a dearth of published literature exploring the predictive value of neutrophil/lymphocyte ratio in the preoperative diagnosis of adnexal/ovarian torsion.
Tis article, therefore, aimed to identify if the diagnostic value of neutrophil/lymphocyte ratio in adnexal torsion in comparison with other untwisted unruptured ovarian cyst.

Methods
Tis was a retrospective study conducted in Grande International Hospital, Kathmandu, Nepal, after obtaining approval from the institutional review committee of the same institute (approval no. 12/2021). Data of all the gynecological surgeries done over a period of fve years from January 1 st 2016 to January 1 st 2020 were retrieved from the record section/department/database of the institute. All the patients who had undergone surgery for adnexal torsion and ovarian cyst confrmed postoperatively were selected. A total of 213 patients were found who had undergone surgery for adnexal torsion and ovarian cyst in that duration. Patients with a suspicion of malignancy [14], ruptured ovarian cyst [15], tubal ovarian abscess [10], comorbidities such as atherosclerotic heart disease, diabetes mellitus, heart disease (30), and recent surgical procedures [13] were excluded from the study because these may have an efect on blood count parameters. Excluding all these cases, a total of 125 cases were included in the study.
Two groups were formed (adnexal torsion (AT, n � 25) and untwisted unruptured ovarian cyst (UOC, n � 100)) and investigated. All the data about the demographic parameters (age, parity, and abortion), hematological parameters (WBC count and diferential counts), operative approach and technique, and the histopathological reports were obtained from the electronic database and documented in a preformed proforma. SPSS was used for data entry and statistical analysis. Normality of data was assessed by Shapiro-Wilk test. In the study, descriptive and categorical data were evaluated as number (n) and percentage (%), and continuous data were studied as interquartile range and medians. Logistic regression analysis and the infuence of each factor on the preoperative diagnosis of AT were evaluated. Receiver operating curve (ROC) analysis was used to evaluate the diagnostic value of neutrophil-lymphocyte ratio in predicting AT. Area under the curve (AUC) was used to determine sensitivity and specifcity of each marker. P value <0.05 was considered as statistically signifcant. Most important factor in determining adnexal torsion was identifed as odds ratio. In the present study, the cut-of value for ROC curve analysis was 3, while it was determined as 8.8 K/L for WBC [16].

Results
Tere were a total of 125 patients included in the study (adnexal torsion n � 25 and untwisted unruptured ovarian cyst n � 100).

Demographic Parameters.
Te median age group of the patient in study group was 30 years. However, in the AT group, it was 32 years and in UOC group 30 years. Most of the cases were nulliparous in both the groups (44% in AT and 45% in UOC). Most cases had no history of abortion in both groups (Table 1). No statistically signifcant diference was seen in both groups in comparison to age, parity, and abortion ( Table 2).

Blood Parameters.
Te median WBC count in the study group was 8070 cells/mm 3 . In the AT group, it was 9950 cells/mm 3 , and in the UOC group, it was 7475 cells/ mm 3 . Neutrophil and lymphocyte levels were 74.40% and 21.20%, respectively, in the AT group and 56.70% and 31.15%, respectively, in UOC group. NLR was 3.47 in AT group and 1.82 in UOC group (Table 3). Tough the median

Discussion
Adnexal torsion, a gynecological emergency, when inaccurately diagnosed could lead to damage of ovaries ultimately afecting the fertility. Complete blood count is the informative proinfammatory marker which is a cheap test and usually performed before every surgery. However, its importance in adnexal torsion has not been studied in detail. Current evidence shows that these blood parameters are useful in diagnosing and prognosticating in case of ischemic diseases such as acute coronary syndrome, acute ischemic stroke, and acute mesenteric ischemia [14,17,18]. Normal Doppler fow can be observed in up to 60% of adnexal torsion cases confusing the diagnosis [19]. Out of the total 125 participants, median age group in the AT group was found to be 30 years supporting the fact that adnexal torsion occurs mostly in the reproductive age group [3]. However, there was no signifcant diference in comparison to UOC group where median age group was 32 years. Tis is in contrast to the study conducted by Soysal and Baki [20] where the median age group in UOC group was 24 years (19-31). Te diference could be because of diferent inclusion and exclusion criteria. Regarding the parity and abortion, there was no statistical diference between the AT and UOC groups. Tis was similar to a study conducted by Ercan et al. [16].
White blood cell count in AT group was not statistically signifcant in comparison to UOC group. Tis fnding is dissimilar to studies conducted by Lee et al., Ercan et al, and Soysal and Baki [5,16,20]. In the present article, unadjusted odds ratio (UOR) of neutrophil count and lymphocyte count showed signifcant diference in both studied groups but adjusted odds ratio (AOR) was not statistically signifcant. Tis is also in contrast to other studies [5,16,20].Tis could be because the logistic regression model was used to evaluate the data where many confounders were excluded. However, confounders could be a hindering factor in their study. A study by Tas et al. [15] had used the similar statistical test which supported our fndings. Discrepancies between the diferent study groups could be because of the  methodological diference, diferent hematological analyzers, variation in inclusion and exclusion criteria, and interval between diagnosis and blood parameter assessment.
Comparing the NLR between two groups, there was a statistically signifcant diference. NLR > 3 was found to be predictive of ATgroup with a moderate sensitivity (76%) and high specifcity (91%) with AUC value (0.835) of good signifcance. If NLR ratio is ≥3, there are 26 times high possibility of adnexal mass being an adnexal torsion. USG and color Doppler have sensitivity of 22%-66%, which is found to be lesser than that of NLR supported by various studies including the present study [5].
NLR has been a popular infammatory marker and is important these days. NLR is superior to WBC in the estimation of undesired outcomes within the infammatory process and surgical conditions [21]. Diferent studies used   Obstetrics and Gynecology International the cut-of value of NLR > 3 as a marker for adnexal torsion [5,16,20]. Te primary pathophysiology in ovarian torsion is ischemia. Following ischemia, reperfusion occurs which may result in the accumulation of the activated neutrophils. Activated neutrophils then release reactive oxygen species [5].
In the torsion of adnexa, ischemia damage to adnexal tissue occurs which produces reactive oxygen species and nitrogen species. Tis leads to leukocyte activation, resulting in further damage and cell death similar to mechanisms which occur in ischemia of the brain and kidney [22].
Operative technique was as per surgeon's preference. Surgeons in our center preferred laparoscopy. Regarding the surgical procedure, most cases underwent cystectomy. In the AT group, 19 cases (76%) underwent oophorectomy, however, infarcted ovary was seen in only 4 cases, suggesting the fact that not all cases need oophorectomy. Tese fndings were similar to a study conducted by Lee et al. [5]. Depending upon the intraoperative fndings and viability of ovarian tissue, conservative surgery can be helpful. Analyzing the HPE reports of the AT group, the commonest fnding was mature cystic teatime followed by serous and mucinous tumor, respectively. Tis was contrary to the study done by Vijayalakshmi et al. where mucinous was seen commonly followed by serous and mature cystic teatime [23]. Mature cystic teatime was found to have undergone more torsion in other studies [24]. Te diferences could be because of lower number of cases in all the studies.
Tus, the strength of the present article is that it included cases of chronic infection and endometriosis cases which could have afected the level of blood parameters. On logistic regression analysis, AOR showed statistically signifcant NLR for adnexal torsion. Te sensitivity and specifcity of NLR showed fairly good supportive results. Tis supported the fact that in emergency settings for proper diagnosis, NLR can be helpful. Moreover, it is much more helpful in low resource settings where facilities of ultrasonography and color Doppler are unavailable and diagnosis is solely based on clinical and hematological parameters.
Te limiting factor of the study is its retrospective nature and small sample size; single center data and symptoms were not included. Moreover, the time interval between symptoms, presentation, blood parameters assessment, and surgery could not be traced. It has been found that the time duration between symptoms and assessment of blood parameters has an efect on the blood parameters. Greater the duration, more the tissue damage and higher the level of blood parameters [5].
Preoperative neutrophil-lymphocyte ratio (NLR) can be a predictive marker for diagnosis of adnexal torsion and can diferentiate adnexal torsion from ovarian cysts.

Data Availability
Te data used to support the fndings of this study are available from the authors.

Conflicts of Interest
Te authors declare that they have no conficts of interest.