Lower maximum standardized uptake value of fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography imaging in pancreatic ductal adenocarcinoma patients with diabetes

The American Journal of Surgery (2015) 209, 709-716

Clinical Science

Lower maximum standardized uptake value of fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography imaging in pancreatic ductal adenocarcinoma patients with diabetes Kwang Hyun Chung, M.D.a, Joo Kyung Park, M.D.b, Sang Hyub Lee, M.D., Ph.D.c, Dae Wook Hwang, M.D., Ph.D.d, Jai Young Cho, M.D., Ph.D.d, Yoo-Seok Yoon, M.D., Ph.D.d, Ho-Seong Han, M.D., Ph.D.d, Jin-Hyeok Hwang, M.D., Ph.D.c,* a

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea; bDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Gangnam Finance Center, 152, Teheran-ro, Gangnam-gu, Seoul 135-984, Republic of Korea; cDepartment of Internal Medicine, dDepartment of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beongil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea

KEYWORDS: Carcinoma; Pancreatic ductal; Diabetes mellitus; Positron emission tomography and computed tomography; Standardized uptake value

Abstract BACKGROUND: The effects of diabetes mellitus (DM) on sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG PET/CT) for diagnosing pancreatic ductal adenocarcinomas (PDACs) is not well known. This study was aimed to evaluate the effects of DM on the validity of 18F-FDG PET/CT in PDAC. METHODS: A total of 173 patients with PDACs who underwent 18F-FDG PET/CT were enrolled (75 in the DM group and 98 in the non-DM group). The maximum standardized uptake values (SUVsmax) were compared. RESULTS: The mean SUVmax was significantly lower in the DM group than in the non-DM group (4.403 vs 5.998, P 5 .001). The sensitivity of SUVmax (cut-off value 4.0) was significantly lower in the DM group than in the non-DM group (49.3% vs 75.5%, P , .001) and also lower in normoglycemic DM patients (n 5 24) than in non-DM patients (54.2% vs 75.5%, P 5 .038).

The authors declare no conflicts of interest. * Corresponding author. Tel.: 182-31-787-7009; fax: 182-31-787-4051. E-mail address: [email protected] Manuscript received December 12, 2013; revised manuscript June 7, 2014 0002-9610/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2014.06.038

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The American Journal of Surgery, Vol 209, No 4, April 2015 CONCLUSION: DM contributes to a lower SUVmax of Ó 2015 Elsevier Inc. All rights reserved.

Pancreatic ductal adenocarcinoma (PDAC) accounts for 7% of cancer deaths worldwide and 8.2% in Korea, with nearly equal numbers of new cases and deaths reported annually.1,2 The location of the pancreas in the retroperitoneal space masks early symptoms, and pancreatic cancer is frequently undetected until prominent clinical signs seem to appear abruptly. The overall 5-year survival in all stages of pancreatic cancer has not improved and remains at approximately 6% in the United States. Over the past 20 years, improvements in surgical techniques and perioperative and postoperative management have decreased surgical mortality, and long-term survival rates after surgery at highvolume pancreas surgery medical centers have improved from 12% to 40% at some instances.3–5 Additionally, fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG PET/ CT) has become an important diagnostic modality in pancreatic cancer management, including differential diagnosis of pancreatic lesions, evaluation of cancer stage, evaluation of treatment response, and assessment of tumor recurrence.6–8 Furthermore, the maximum standardized uptake value (SUVmax) of 18F-FDG PET/CT is correlated with the overall survival of pancreatic cancer patients.9,10 18 F-FDG PET/CT is a noninvasive imaging technique that can scan the entire body in 1 session and is a wellaccepted imaging modality used for diagnosis, staging, and evaluation of treatment response in several different types of malignancy.11–13 18F-FDG imaging of cancer relies on a molecular shift in glucose transporters in malignant cells, resulting in increased uptake of glucose within the tumor. 18F-FDG is transported into cells in a manner similar to glucose; therefore, the relatively high metabolic activity and increased uptake of glucose in malignant cells enable differentiation of cancer tissue from normal tissue. 18FFDG PET/CT can be used to measure the amount of 18FFDG uptake in malignant tissue, and the maximum amount of 18F-FDG uptake is calculated as SUVmax.14 However, some issues have to be considered. The biodistribution of 18 F-FDG may be affected by various conditions that alter normal tissue metabolism, such as hyper/hypoglycemia, local inflammation or infection, diabetes mellitus (DM), and administration of insulin or oral hypoglycemic agents.15–17 Several in vitro and in vivo studies have reported that the uptake of 18F-FDG in cancer cells declines with increase in glucose level in the medium or blood and that insulin loading decreases the 18F-FDG uptake into the tumor cells in an animal model.18–21 Clinical studies have shown that compared with normoglycemia, hyperglycemia is associated with a higher false negative rate of 18F-FDG PET/CT in the evaluation of malignancy and decreased sensitivity in detecting pancreatic cancer.22 However, most of the human data need to be analyzed to determine

18

F-FDG PET/CT in patients with PDACs.

whether hyperglycemia or DM can influence the detection of malignancy, especially in pancreatic cancer, because up to 80% of pancreatic cancer patients have hyperglycemia or DM, even in the presymptomatic phase.23 The aim of this study was to investigate whether DM can affect the functional role of 18F-FDG PET/CT as a diagnostic tool in patients with PDACs.

Patients and Methods Patients Patients who had pathologically confirmed PDACs and underwent 18F-FDG PET/CT as a diagnostic work-up were enrolled as study subjects between September 2005 and March 2012 at Seoul National University Bundang Hospital. Patient demographics, serum biochemistry, radiologic results including 18F-FDG PET/CT and histologic findings were retrospectively reviewed. The exclusion criteria were as follows: subcentimeter-sized small cancer at CT scan, prior history of anticancer treatment (eg, surgical resection, systemic chemotherapy, or radiotherapy) before undergoing 18F-FDG PET/CT, or presence of pancreatic cystic tumors or pancreatic neuroendocrine tumors. DM was diagnosed from the patients’ clinical histories and laboratory test results (hemoglobin A1c [HbA1c] R 6.5%; fasting plasma glucose R 126 mg/day; or 2-hour plasma glucose R 200 mg/dL in repeated testing, following the Standards of Medical Care in Diabetes of the American Diabetes Association).24 The study was approved by the Institutional Review Board of Seoul National University Bundang Hospital and conformed to the ethical guidelines of the Declaration of Helsinki, 1964, as revised in 2004. The requirement for informed consent was waived.

Study design The patients were divided into 2 groups (DM vs nonDM group), and the SUVmax was compared between the 2 groups. Other confounding factors that may influence glucose uptake of cancer tissue, such as plasma glucose level or cancer stage, were identified. Demographic and clinical data, including sex, age, body mass index (BMI), hypertension, smoking and alcohol consumption history, serum levels of carbohydrate antigen 19-9 (CA 19-9), location of the tumor (head, body, and tail), and the longest diameter of the tumor measured with CT scan, were obtained. The 7th edition of the tumor-node-metastasis system from the American Joint Committee on Cancer was used to determine the clinical stage of the study patients.25

K.H. Chung et al.

PET/CT in pancreatic cancer with DM

Imaging protocol and data analysis of fluorine18 fluorodeoxyglucose positron emission tomography coupled with computed tomography All 18F-FDG PET/CT imaging was performed before the initiation of anticancer therapy (eg, surgery, chemotherapy, or radiotherapy). The preparation protocol was strictly followed by the study patients. Patients fasted at least 6 hours before intravenous administration of 18F-FDG (5.18 MBq/ kg of body weight), and the plasma glucose level of each patient was measured just before the injection of 18FFDG. Whole-body PET images were acquired with a conventional 18F-FDG PET three-dimensional protocol using a Discovery VCT scanner (General Electric Medical Systems, Milwaukee, WI) at 50 minutes after 18F-FDG administration. The resulting PET and CT images were coregistered on hardware. Low-dose CT was used to scan the region from the head to thigh (tube voltage 120 kV, tube-rotation time .5 seconds per rotation, pitch factor .5625:1, and helical thickness 3.75 mm, which matched the thickness of the PET image section). Low-dose CT was performed for attenuation correction and anatomic localization without using intravenous contrast material and with no breath holds. Immediately after CT, emission PET images were acquired for 2 minutes and 30 seconds per each bed in a three-dimensional acquisition mode. Table 1

711 Transaxial images of the patients were acquired for 17 minutes and 30 seconds and quantitatively analyzed. 18F-FDG PET/CT data were analyzed using the SUVmax, which was calculated as decay-corrected activity (kBq) per milliliter of tissue per volume injected 18F-FDG activity (kBq) per body mass (g). To analyze FDG accumulation, a circular region of interest was drawn by a board-certified nuclear medicine physician over the primary mass lesions in pancreas on transaxial images on a slice-by-slice basis, so as to cover whole lesion.

Statistical analysis Baseline characteristics of the 2 groups were compared with a chi-square test and Fisher’s exact test (when appropriate) to compare the frequencies of nominal variables and with an independent t test to compare the mean 6 standard deviation of the continuous quantitative variables. To determine the independent factors that affect SUVmax, patients were divided using an SUVmax of 4.0 as a cut-off value.26 Differences in clinical factors and laboratory factors between patients whose SUVmax was greater than or equal to 4.0 and the patients whose SUVmax was less than 4.0 were compared by univariate analysis. These variables included the following: sex, age, BMI, DM, hypertension, cigarette smoking history, binge alcohol consumption

Patient characteristics

Male (%) Age (year)* BMI (kg/m2)* Hypertension Smoking Never smoker Current smoker Ex-smoker Binge drinker Glucose (mg/dL)* CA 19-9 (mg/dL)* Location Head Body Tail Size (mm)* SUVmax* Stage IA or IIB II IV Resectability Resectable Borderline Unresectable R0 resection

DM (n 5 75)

Non-DM (n 5 98)

P value

43 (57.3%) 66.6 6 9.38 22.57 6 2.808 44 (58.7%)

58 (59.2%) 63.9 6 11.30 21.87 6 2.904 29 (29.6%)

.807 .105 .118 ,.001

49 (65.3%) 15 (20.0%) 11 (14.7%) 3 (4.0%) 148.5 6 41.65 2,505.5 6 5,158.37

64 (65.3%) 24 (24.5%) 10 (10.2%) 3 (3.1%) 105.5 6 13.94 2,287.1 6 4,858.27

43 (57.3%) 20 (26.7%) 26 (34.7%) 35.3 6 13.12 4.403 6 2.0206

46 (46.9%) 28 (28.6%) 39 (29.8%) 37.9 6 19.12 5.998 6 3.8769

.175 .782 .490 .305 .001

35 (46.7%) 14 (18.7%) 26 (34.7%)

39 (39.8%) 20 (20.4%) 39 (29.8%)

.660

23 14 38 28

32 7 59 33

.068

(30.7%) (18.7%) (50.7%) (37.3%)

(32.7%) (7.1%) (60.2%) (33.7%)

BMI 5 body mass index; CA 19-9 5 carbohydrate antigen 19-9; DM 5 diabetes mellitus; SUVmax 5 maximum standardized uptake value. *Values are expressed as mean 6 standard deviation.

.584

.738 ,.001 .776

.618

712 history (alcohol R 80 g/week), plasma glucose level, serum CA 19-9 level, tumor location (head, body, tail), the longest diameter of the tumor, cancer stage, resectability, and R0 resection rate. Variables found to be significant in univariate analysis were subsequently assessed by stepwise logistic regression to identify factors that were independently associated with the SUVmax of 18F-FDG PET/CT. To eliminate the effect of plasma glucose concentration on SUVmax, we compared non-DM group with DM patients with normoglycemia (plasma glucose level , 126 mg/dL) at the time of 18F-FDG PET/CT using a chi-square test. The breakpoint of 126 mg/dL was determined according to the American Diabetes Association criteria of fasting plasma glucose cut point. Statistical analysis was performed using the PASW Statistics program (version 18.0.0; IBM Corp., Armonk, NY). A P value less than .05 was considered statistically significant.

The American Journal of Surgery, Vol 209, No 4, April 2015

A 35.0%

30.0%

25.0%

20.0% Non DM

15.0%

DM

10.0%

5.0%

0.0% <2.0

2.0 ~ 2.9

3.0 ~3,9

4.0 ~ 4.9 SUVmax

5.0 ~ 5.9

6.0 ~ 6.9

7.0 ~

B SUVmax ≥ 4.0: 49.3% DM 2.7% 14.7%

33.3%

17.3%

16.0%

9.3% 6.7%

<2.0 2.0 ~ 2.9 3.0 ~3,9

SUVmax ≥ 4.0: 75.5%

Results

4.0 ~ 4.9 5.0 ~ 5.9

Non DM 3.1% % 9.2%

12.2%

18.4%

20.4%

11.2%

25.5%

6.0 ~ 6.9 7.0 ~

Patients The baseline clinical characteristics and tumor status of the patients were summarized in Table 1. Among the study population of 173 patients, 75 had been previously diagnosed with DM or fulfilled the diagnostic criteria of DM at the time of pancreatic cancer diagnosis, and 98 patients did not have DM. All the DM patients are of type II DM and 3 of them were using insulin for blood sugar control but discontinued 24 hours before the PET/CT scan. Sixtysix patients underwent operations: 58 patients with curative intention, 4 patients for palliative purposes, and 4 patients were found to have disseminated disease during the operation. The following demographic and clinical factors had no significant difference between the 2 groups (DM vs nonDM group): sex, age, BMI, hypertension, smoking history, alcohol consumption habits, CA 19-9 level, tumor locations, tumor stages, tumor size, and R0 resection rate. Plasma glucose levels and the prevalence of hypertension were significantly greater in the DM group than in the non-DM group.

Comparison of the distribution of maximum standardized uptake value between the diabetes mellitus and non-diabetes mellitus groups The mean SUVmax of the DM and non-DM groups was 4.403 and 5.998, respectively (P 5 .001), and the distributions of SUVmax were described in Fig. 1A. The peak frequency was observed at an SUVmax of 3.0 to 3.9 in pancreatic cancer patients with DM. However, an SUVmax of greater than or equal to 7.0 was most frequently observed in pancreatic cancer patients without DM. Seventy-four of the 98 (75.5%) non-DM patients had an SUVmax of greater than or equal to 4.0. In contrast, only 37 of the 76 (49.3%) patients in the DM group had an

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Figure 1 Distribution of SUVmax among pancreatic cancer patients with and without DM. (A). The peak frequency was observed at an SUVmax of 3.0 to 3.9 in pancreatic cancer patients with DM, and the frequency decreased gradually with the increase in SUVmax. However, an SUVmax of greater than or equal to 7.0 was most frequently observed in pancreatic cancer patients without DM. (B) Seventy-four of the 98 (77.5%) non-DM patients had an SUVmax of greater than or equal to 4.0, and 25 (25.5%) patients had an SUVmax greater than 7.0. In contrast, only 37 of the 75 (49.3%) patients in the DM group had an SUVmax greater than 4.0, and there was statistical significance between the 2 groups (P , .001).

SUVmax greater than 4.0, and there was statistical significance between the 2 groups (P , .001) (Fig. 1B).

Factors associated with the maximum standardized uptake value of fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography in pancreatic cancer The clinical and laboratory factors were assessed by univariate analysis for determining associations with the SUVmax of 18F-FDG PET/CT in pancreatic cancer (Table 2). A low SUVmax (,4.0) was significantly associated with the following variables: female sex (P 5 .046), DM (P , .001), hypertension (P 5 .061), elevated plasma glucose level (P 5 .012), smaller tumor size (P , .001), and lower cancer stage (P 5 .024). Other factors such as age, BMI, cigarette smoking history, alcohol consumption habits (alcohol .80 g/week), serum CA 19-9 level, and tumor location (head, body, tail) did not affect the SUVmax. Multivariate analysis revealed that the presence of DM was related to a low SUVmax (odds ratio 3.308; 95%

K.H. Chung et al. Table 2

PET/CT in pancreatic cancer with DM

713

Clinical and laboratory factors associated with SUVmax by univariate analysis

Male Age (year)* BMI (kg/m2)* DM Hypertension Smoking Current smoker Ex-smoker Never smoker Binge drinker Glucose (mg/dL)* CA 19-9 (mg/dL)* Location Head Body Tail Size (mm)* Stage IIA or IIB III IV Resectability Resectable Borderline Unresectable R0 resection

SUVmax R 4.0 (n 5 111)

SUVmax , 4.0 (n 5 62)

P value

71 (64.0%) 64.7 6 10.40 21.96 6 2.761 37 (33.3%) 41 (36.9%)

30 (48.4%) 65.7 6 10.90 22.56 6 3.053 38 (61.3%) 32 (51.6%)

.046 .546 .184 ,.001 .061

28 (25.2%) 15 (13.5%) 68 (61.3%) 4 (3.6%) 118.1 6 27.15 2,615.3 6 5,209.74

11 (17.7%) 6 (9.7%) 45 (72.6%) 2 (3.2%) 134.7 6 46.83 1,969.0 6 4,548.39

57 (51.4%) 29 (26.1%) 46 (41.4%) 39.8 6 18.50

32 (51.6%) 19 (30.6%) 19 (30.6%) 31.2 6 11.35

41 (36.9%) 20 (18.0%) 50 (45%)

33 (53.2%) 14 (22.6%) 15 (24.2%)

.024

29 12 70 33

26 9 27 28

.043

(26.1%) (10.8%) (63.1%) (29.7%)

(41.9%) (14.5%) (43.5%) (45.2%)

.325

.896 .012 .415 .974 .524 .160 ,.001

.042

BMI 5 body mass index; CA 19-9 5 carbohydrate antigen 19-9; DM 5 diabetes mellitus; SUVmax 5 maximum standardized uptake value. *Values are expressed as mean 6 standard deviation.

confidence interval 1.634 to 6.695). In addition, tumor size was also associated with a low SUVmax (odds ratio 1.040, 95% confidence interval 1.007 to 1.074) (Table 3). Female sex and hypertension showed a significant correlation with lower SUVmax; however, these statistical significances were eliminated by multivariate analysis. When performing further analysis of the relation between HbA1c and SUVmax of 18F-FDG-PET/CT in DM patients, patients with HbA1c ,7% showed higher 18F-FDG PET/CT sensitivity than in patients with HbA1c R7% (71.4% vs 45.1%, P 5 .081), although these difference in sensitivity did not reach statistical significance.

Table 3

Comparison of non-diabetes mellitus group and diabetes mellitus group with normoglycemia (plasma glucose level , 126 mg/dL) at the time of fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography study At the time of 18F-FDG PET/CT study, 24 of the 74 patients in the DM group were normoglycemic (plasma glucose level , 126 mg/dL) and 50 of the 74 patients were hyperglycemic (plasma glucose level R 126 mg/

Clinical and laboratory factors associated with SUVmax by multivariate analysis

Sex Age BMI DM Tumor size Stage IIA or IIB Stage III Stage IV

Coefficient

Standard error

Odds ratio (95% CI)

P value

2.558 .002 2.059 21.196 .039

.428 .017 .065 .360 .017

.572 1.002 .943 .302 1.040

2.053 .481

.463 .511

.948 (.383–2.349) 1.617 (.594–4.400)

.192 .899 .365 .001 .018 .561 .909 .347

(.247–1.324) (.969–1.037) (.830–1.071) (.149–.612) (1.007–1.074)

BMI 5 body mass index; CI 5 confidence interval; DM 5 diabetes mellitus; SUVmax 5 maximum standardized uptake value.

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Table 4

Comparison of SUVmax between non-DM and DM patients with a plasma glucose level less than 126 mg/dL

Non-DM (n 5 98) DM (n 5 24)

SUVmax , 4

SUVmax R 4

P value

24 (24.5%) 11 (45.8%)

74 (75.5%) 13 (54.2%)

.038

DM 5 diabetes mellitus; SUVmax 5 maximum standardized uptake value.

dL). About 54.2% of the DM patients with normoglycemia (13 of 24) and 75.5% of the non-DM patients (74 of 98) had an SUVmax greater than 4.0 (P 5 .038) (Table 4).

Comments 18

F-FDG PET/CT has become one of the most important tools in the work-up processes and management of PDACs, such as differential diagnosis, evaluation of cancer stage, treatment response, or tumor recurrence.6–8 However, it is unclear whether DM can influence the SUVmax or the sensitivity of 18F-FDG PET/CT in the diagnosis of pancreatic

cancer. This study showed a significantly lower SUVmax of 18F-FDG PET/CT in the DM group than in the nonDM group for the diagnosis of PDAC. With an SUVmax cut-off value of 4.0, lower 18F-FDG PET/CT sensitivity was observed in the DM patients than in non-DM patients for diagnosis of PDAC. In addition, these results showed consistently in patients who did not have elevated plasma glucose levels at the time of the 18F-FDG PET/CT. Therefore, we suggest that DM might be a significant factor that lowers the SUVmax and sensitivity of 18F-FDG PET/CT in the diagnosis of PDACs. Many studies have attempted to differentiate malignant lesions from benign lesions such as inflammation or

Figure 2 (A) A 55-year-old male patient without diabetes mellitus. A hypodense pancreatic head mass (black arrow) was seen on arterial helical CT and increased 18F-FDG uptake in the pancreatic head mass (white arrow) on 18F-FDG PET/CT (SUVmax 7.4; TNM stage T4N0M0). (B) A 66-year-old male patient with diabetes mellitus. A hypodense pancreatic head mass (black arrow head) was seen on arterial helical CT; however, there was no hypermetabolic lesion on 18F-FDG PET/CT (TNM stage T4N0M0).

K.H. Chung et al.

PET/CT in pancreatic cancer with DM

infection using the SUVmax of 18F-FDG PET/CT.26–31 In one study, mean SUVmax was higher for pancreatic cancer than for chronic pancreatitis, and sensitivity and specificity for pancreatic cancer were 89% and 53% with an SUVmax cut-off value of 2.9.27 Another group reported that an SUVmax of 3.5 was the best cut-off value for differentiation between benign and malignant lesions.29 Another study reported 96% and 100% for the sensitivity and specificity for differentiation between benign and malignant lesions, with an SUVmax cut-off value of 4.0, which was the same cut-off value used in our study.26 Despite all these findings, there are many obstacles in distinguishing PDACs from other benign lesions using the SUVmax alone, and 18F-FDG uptake may be overlapped between inflammatory and malignant lesions in many cases.32,33 One of the most valid explanations is that 80% of patients with PDACs have DM or impaired glucose tolerance at the time of diagnosis, which can influence 18F-FDG uptake into the target lesions. In this study, we set the cut-off value of SUVmax as 4.0 for the diagnosis of PDACs, and the sensitivity of SUVmax was significantly lower in the DM group than in the nonDM group (49.3% vs 75.5%, respectively, P , .001). This implies that an SUVmax of 4.0 may not be the best cutoff value for PDACs combined with DM, due to false negative results. Furthermore, 18F-FDG PET/CT would be less sensitive for diabetic pancreatic cancer patients whose glucose levels have not been well controlled rather than all DM patients. On the other hand, our data suggest that an SUVmax of 4.0 is very valuable as a cut-off value in the diagnosis of PDACs in the absence of DM (Fig. 2). By lowering the cut-off value to 3.196, the sensitivity of SUVmax of DM group raises up to similar to that of nonDM group (75.5%). However, it should be considered that concomitant increase of false positivity could not be avoidable. Glucose uptake by malignant cells is largely mediated by the GLUT-1 transporters.34–37 Interestingly, a recent study showed that chronic hyperglycemia downregulates GLUT-1 expression at both messenger RNA and protein levels in the rat brain and therefore causes low uptake of glucose in both cancer cells and normal cells.38 Eventually, this low uptake would result in a lower SUVmax, as seen in our study results. In this study, besides the presence of DM, smaller tumor size was associated with a low SUVmax. This finding of our study corresponds with the results of earlier studies, which reported that the tendency of SUVmax positively correlates with tumor size or tumor staging before treatment.39,40 Our study showed the influence of DM on the diagnostic capability of 18F-FDG PET/CT for PDACs in a large study population. So we may expect our results to be useful for practice although there are several limitations in our study such as analyses of these data in a retrospective fashion and no comparable negative control (chronic pancreatitis or autoimmune pancreatitis).

715 In conclusion, DM contributes to a lower SUVmax of F-FDG PET/CT in patients with PDACs; this finding suggests that 18F-FDG PET/CT results would be carefully interpreted when used for diagnosing PDACs in DM patients. 18

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31.

32. 33.

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