Ağustos 2024

23-28

Mehmet Önder EKMEN¹, Serdar KARAKAYA², Evrim KAHRAMANOĞLU AKSOY¹

Departments of ¹Gastroenterology and ²Medical Oncology, Ankara
SBU Atatürk Sanatorium Training and Research Hospital, Ankara, Turkey

Giriş ve Amaç: Bu çalışmada, tümör görüntüleme sırasında tesadüfen 18-floro-2-deoksiglukoz tutulumu tespit edilebildiğinden, kolon tutulumu nedeniyle kolonoskopi yapılan hastaların pozitron emisyon tomografi/bilgisayarlı tomografideki bulgularının değerlendirilmesi amaçlandı. Gereç ve Yöntem: Bu prospektif çalışmaya toplam 84 hasta dahil edildi. Kolonoskopi yapılan hastalarda hematolojik parametreler ve bunların maligniteye etkileri incelendi. Demografik özellikler ve pozitron emisyon tomografi/bilgisayarlı tomografi tutulum bölgeleri laboratuvar parametreleriyle karşılaştırıldı. Bulgular: Endoskopi öncesi kanseri öngörmede gastrointestinal sistem maksimum standardize tutulum değeri önemliydi (eğri altında kalan alan: 0.738, p = 0.001), Nötrofil/lenfosit oranı (eğri altında kalan alan: 0.659, p = 0.033), trombosit/lenfosit oranı (eğri altında kalan alan: 0.657, p = 0.035) aynı zamanda endoskopi öncesi kanseri öngördü. Her üç tanısal test de klinik öngörücülüğü gösterdi; gastrointestinal sistem maksimum standardize tutulum değeri en yüksek ayırt etme gücüne sahipti. Lojistik regresyon analizi, gastrointestinal sistem maksimum standardize tutulum değerindeki artışın kanser olasılığını 1.179 kat (p = 0.004), nötrofıl lenfosit oranı değerindeki artışın ise kanser olasılığını 1.108 kat (p = 0.007) artırdığını ortaya koydu. Sonuç: Bu araştırma, premalign/malign kolon patolojilerinde gastrointestinal sistem maksimum standardize tutulum değeri, nötrofıl lenfosit oranı ve trombosit/lenfosit oranı ‘nin öngörü potansiyelini ortaya koymuştur.

PET/BT, kolon kanseri, SUVmax, NLR (nötrofıl lenfosit oranı), PLR (Trombosit lenfosit oranı)

Colorectal cancers are the third most common cancer among newly diagnosed cancer patients, after prostate and lung cancers in men and breast and lung cancers in women (1). Metastases are detected in approximately half of colorectal cancer patients within the first five years after diagnosis. In addition to anatomical methods such as ultrasonography (USG), computerized tomography (CT), magnetic resonance imaging, and positron emission tomography/computerized tomography (PET/CT) have been widely used in the detection of these metastases in recent years (2,3). Based on the increased use of glucose in malignant tissues, 18-fluoro-2-deoxyglucose (FDG) PET/CT is used as a non-invasive method in the follow-up of treatment response, as well as diagnosis and staging (4). However, since FDG is not a tumor-specific agent, it is known that it can also be involved in benign conditions, and this situation may cause diagnostic confusion (5). Positron emission tomography (PET) is a non-invasive functional imaging technique that investigates the presence of malignant tumors. Fluorodeoxyglucose and PET play an active role in determining the diagnosis, staging, and response to treatment, revealing tumor aggressiveness, and detecting the radiotherapy area. FDG is retained in higher concentrations in tumors than in normal tissue and is easily detected as high-count foci in FDG-PET images (5,6). Although it varies from person to person, there may be physiologically diffuse or segmental colon involvement in the intestines. Due to the high sensitivity of PET examination performed for a different purpose, focal or nodular hypermetabolic lesions detected in the gastrointestinal system (GIS) have been reported to have a high probability of premalignant/malignant lesions such as a hyperplastic polyp, villous adenoma, or carcinoma. Therefore, colonoscopic evaluation of incidentally detected focal or nodular lesions is recommended (7). As 18-fluorodeoxyglucose PET/CT scans the whole body apart from becoming a frequently used method for tumor imaging, staging, and follow-up, it can incidentally detect malignities. Incidental FDG uptake was detected in 3.6% of the patients in PET/CT to evaluate non-gastrointestinal system diseases. False positive involvements were detected in approximately 9.3% to 63% of patients. Rigault et al. detected at least one lesion on colonoscopy in 46 of 70 patients with incidental focal colorectal FDG uptake (8). Kunawudhi et al. reported the positive predictive value of PET/CT as 48% for colon neoplasms (9). Putora et al. detected colonoscopic lesions in 44 of 51 patients with colonic involvement (10). Within the scope of this research, we aimed to evaluate the findings of patients who underwent colonoscopy due to colon involvement in PET/CT.

<p>In this study, hematological parameters were monitored inpatients who underwent colonoscopy due to colon involvement in PET/CT, and their effects on malignancy were examined. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Ethics committee approval has been granted from our institution with protocol number 14/465-18, and informed consent has been obtained from all participants.</p><p>Hematological laboratory parameters of the patients were collected. Demographic characteristics of the patients (age,gender, comorbid disease) and involvement sites in PET/CT were compared with laboratory parameters.</p><p><br></p><p><b>Statistical Analysis </b></p><p>The SPSS (Statistical Package for Social Sciences) program was used to evaluate the data. Descriptive statistical methods(mean, standard deviation) and the quantitative data of normal distribution were compared with the Student’s t-test-the Mann-Whitney U-test was utilized for non-normally distributed parameters. Pearson correlation analysis was conducted for parametric measures and Spear man correlation analysis for non parametric values to determine the relationship.</p><p>Student T Test, Mann Whitney U Test, and Spear man Correlation Analysis were used during univariate analysis of patients with and without cancer in order to predict malign ancybefore colonoscopy. In multivariate analysis, the independent variables in predicting cancer using possible factors were analyzed using logistic regression analysis. The Hosmer-Lemeshow test was performed for model fit. A p-value < 0.05 was considered statistically significant</p>

A total of 84 patients have been enrolled in this prospective study. The patients were analyzed according to the presence of cancer; 23.8% (n = 20) were cancer patients, and 76.2% (n = 64) did not have cancer. The mean age of 84 patients was 67.8 ± 9.5 years (43 – 92 years), with no statistically significant difference (Table 1). <br><br> The mean maximum standardized uptake (SUVmax) value of the patients (pleural mass) was 10.42 ± 6.63 (0 - 27.2), with no significance between cancer patients and other individuals. The median gastrointestinal system (GIS) SUVmax value of cancer patients was 10.85 [interquartile range (IQR) = 6.92], while the median GIS SUVmax value of the other subjects was 7.65 (IQR = 4.65), and there was a statistically significant difference (p = 0.001). <br><br> The white blood cell (WBC) of the cancer patient group was 8.08 ± 2.95 x 1000/µl (4.4 - 13.9), and the mean WBC of the other group was 7.67 ± 2.88 x 1000/µl (3.7 - 15.20). There was no statistically significant difference between the mean of the two groups. The neutrophil count of the cancer patients was 5.85 x 1000/µl (IQR = 4.67) and 5.97 x 1000/µl (IQR = 3.52), with no difference between the two groups. The lymphocyte count of the cancer patient group was 0.44 x 1000/µl (IQR = 0.43), and the lymphocyte count of the other group was 0.91 x 1000/µl (IQR = 0.76), and the difference was statistically significant (p < 0.05). The neutrophil to lymphocyte ratio (NLR) of the cancer patient group was 11.55 (IQR = 25.07), and the median of the other individuals was 7.11 (IQR = 9.81), with a statistical significance. The platelet to lymphocyte ratio (PLR) of cancer patients was 461.66 (IQR = 437.2), and the PLR of the other group was 283.59 (IQR = 285.73) (p = 0.035). <br><br> There was no significant difference between the two patient groups regarding endoscopy findings by gender. On the other hand, endoscopy findings were clinically different according to the type of involvement (p < 0.001). The cancer rate of those with diffuse involvement was higher than those with focal involvement (52.4% and 14.3%, respectively). The presence of adenomatous polyps or hyper polyps was similar between the groups (Table 2). <br><br> As a result of the receiver operating characteristic (ROC) analysis, it has been observed that the GIS SUVmax value is important in predicting cancer before endoscopy [area under curve (AUC): 0.738, 95: 0.626 - 850, p = 0.001]. NLR predicted cancer before endoscopy (AUC: 0.659, 95: 0.523 - 0.795, p = 0.033). The PLR was important in predicting cancer before endoscopy (AUC: 0.657, 95: 0.523 - 0.791, p = 0.035). All three diagnostic tests were important in terms of clinical predictivity. However, since the area of the GIS SUVmax value was bigger than the others, its distinctiveness power was higher. However, it is used as a diagnostic with high specificity and sensitivity to rule out other situations (Table 3) (Figure 1) <br><br> A total of 84 patients (20 cancer, 64 control) were included in the study. In the logistic regression analysis, the p-value of the GIS SUVmax value was significant (p = 0.004), and one unit increase in the GIS SUVmax value increased the probability of cancer by 1.179 times. The p-value of the NLR (p = 0.007) was significant, and one unit increase in the NLR value increased the probability of cancer 1.108 times. In the logistics regression analysis (LRA), the model created with only constant predicted 76.2% of the observed values correctly; hence, our model provided significant coefficients and the correct estimation of 78.6% of the observed values (Table 4)

The accuracy of preoperative staging in colorectal cancer (CRC) is very important in guiding the treatment. Therefore, imaging methods are expected to fully evaluate the localization, borders, and local and distant metastasis (11). Patients with CRC present with 20% metastases at the time of diagnosis, and these patients should be evaluated for distant metastases covering the whole body. However, imaging methods currently can only meet some of these expectations among the anatomical imaging methods. FDG-PET allows wholebody imaging in a single session. There is an increase in glucose consumption due to anaerobic glycolysis in malignant cells. This increase can be transferred to radiolabeled glucose imaging methods (12). Especially in patients with CRC who are followed up for recurrence, the tumor size can be detected with FDG-PET before it reaches the dimensions that conventional imaging methods can detect, and the patient’s chance of curative resection increases (13). <br><br><br>However, it should be kept in mind that images with high metabolic properties detected in PET/CT, especially in metabolic terms, are not always specific to malignancy, and similar images can be obtained in the presence of inflammation and infection. It is also known that PET/CT may give false negative results, especially in malignancies with lower grades and low proliferation rates. For this reason, PET/CT results should be evaluated together with the patient’s tumor type and clinical presentation by the clinician (14). In our study, the median GIS SUVmax value of cancer patients was 10.85 (IQR = 6.92), while the median GIS SUVmax value of the other subjects was 7.65 (IQR = 4.65), and there was a statistically significant difference. As a result of the ROC analysis, it has been observed that the GIS SUVmax value is important in predicting cancer before endoscopy. In the logistic regression analysis, the p-value of the GIS SUVmax value was significant, and one unit increase in the GIS SUVmax value increased the probability of cancer by 1.179 times. However, since the area of the GIS SUVmax value was bigger than NLR and PLR, its distinctiveness power was higher. <br> <br>Changes in peripheral blood, such as neutrophilia, lymphopenia, and thrombocytosis, were evaluated in response to systemic inflammation. Since the physiological response of leukocytes to stress causes an increase in the number of neutrophils and a decrease in the number of lymphocytes, the ratio of these two subgroups to each other is used as an inflammatory marker. Thrombocytosis occurs as a result of proinflammatory cytokines stimulating megakaryocytes (15). In this context, studies on new parameters obtained from routine complete blood count, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) have been frequently conducted in various cancer types recently. These parameters depend on the complex relationship between the tumor’s local environment and the host’s inflammatory response and may predict early tumor relapse and mortality (16). Some studies have focused on the neutrophil/ lymphocyte ratio and platelet/lymphocyte ratio, which are considered among the markers of the systemic inflammatory response, and it has been shown that there is a relationship between these markers and the progression of the disease in patients with operated colorectal cancer. In other studies, a preoperative neutrophil/lymphocyte ratio of more than 4 or 5 in ovarian and lung cancers other than colorectal cancer has been found to be associated with an unfavorable prognosis, and an increase in the platelet/lymphocyte ratio is shown as a negative prognostic factor (17). <br> <br>Other studies on CRC have reported that low NLR is associated with better disease-free survival (DFS) outcomes compared with patients with higher rates. In contrast, high NLR is associated with an independent prognostic factor and poor prognosis (18-20). <br> <br>Kwon et al. reported that in preoperative NLR and PLR in colorectal cancers, preoperative elevated PLR reflected increased inflammatory response in response to more aggressive tumor biology (21). Smith et al. showed that high preoperative serum carbohydrate antigen (CA) 19-9 level and increased PLR in cases with pancreatic adenocarcinoma indicate a poor prognosis at one-year survival (22). <br> <br>Systemic inflammation triggers lymphopenia and causes an increase in NLR levels. NLR levels may be a prognostic determinant factor for cancer, and the use of anti-inflammatory drugs in the perioperative period may yield good results in terms of prognosis (16). In a previous study, NLR values in CRC patients were significantly higher than in the control group. These findings were consistent with the literature. The cut-off value for the NLR value was 5 (23). Halazun et al. stated that the cut-off value was accepted as 5 for the NLR value in 440 patients with liver metastasis of colorectal cancer (24). Chiang et al. found a cut-off value of 3 for the NLR value in 3857 colorectal cancer patients. It is thought that this difference may be due to factors such as geography, nutrition, environment, and genetics, which are thought to play a role in the development of CRC, and the data that each patient’s immune response to cancer cells is different (25). In our study, NLR and PLR predicted cancer before endoscopy. One unit increase in the NLR value increased the probability of cancer 1.108 times. <br><br>This research elaborated on the predictivity potential of GIS SUVmax, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio in premalignant/malignant colon pathologies. All three diagnostic tests, GIS SUVmax, NLR, and PLR, were important in clinical predictivity. However, since the area of the GIS SUVmax value was bigger than NLR and PLR, its distinctiveness power was higher. <br><br>Ethics: This study protocol was approved by Ethics Committee of Ankara Keçiören Keçiören Training and Research Hospital (Date: 22.06.2021, and number KAEK –14/465-18.). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all participants. <br><br>Conflicts of interest: The authors declare that they have no conflicts of interest. <br><br>Funding: There is no specific funding related to this research.

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