Delayed 18F-FDG PET/CT Appearance of Urachal Adenocarcinomas

Background Urachal carcinoma is a rare urological malignancy. Use of 18F-FDG PET/CT in urological oncology has developed slowly because of the urinary elimination of 18F-FDG. We investigated whether delayed postdiuretic 18F-FDG PET/CT could be used for diagnosing urachal carcinoma. Methods This retrospective study included 6 patients who underwent delayed postdiuretic 18F-FDG PET/CT for the evaluation of urachal carcinoma. The delayed postdiuretic PET/CT parameters and clinical characteristics of urachal carcinoma were investigated. Results There was no significant difference in the SUVmax between the primary tumors and the urine in the bladder before delayed diuresis (25.4 ± 19.5 vs. 42.9 ± 31.1, P=0.18). However, the SUVmax of the primary tumors was significantly higher than the SUVmax of urine after delayed diuresis (25.4 ± 19.5 vs. 3.5 ± 1.6, P=0.002). Diuretic 18F-FDG PET/CT was positive in all patients when compared with normal liver tissues or urine after delayed diuresis. The SUVmax, TLR, and TUR of the primary tumors were 25.4 (range: 7.2–58.9), 7.0 (range: 1.8–14.7), and 6.8 (range: 3.8–11.3), respectively. Delayed postdiuretic 18F-FDG PET/CT had a negative predictive value of 100% (5/5) for predicting lymph node metastasis. One patient received chemotherapy after radical resection of urachal carcinoma because 18F-FDG PET/CT found lung metastases, and one patient only received chemotherapy because PET/CT found peritoneal and skeletal metastases. Conclusions Delayed postdiuretic 18F-FDG PET/CT is a useful tool for the preoperative evaluation of urachal carcinoma. 18F-FDG PET/CT may improve clinical decision making and management of urachal carcinomas.


Introduction
Urachal carcinoma is a rare urological malignancy accounting for only 0.34% of all bladder neoplasms, which extends from the bladder dome to the umbilicus [1,2]. e most common histologic type of urachal carcinoma is adenocarcinomas. Computed tomography and magnetic resonance imaging are the commonly used imaging modalities for the diagnosis of urachal carcinoma [2,3]. 18 Ffluorodeoxyglucose (FDG) positron emission tomography (PET) has become a useful modality in cancer evaluation based on hypermetabolism observed in malignant cells [4]. However, use of 18 F-FDG PET/CT, specifically in urological oncology, has developed relatively slowly because the radiotracer is excreted into the urine and bladder, making structures and original tumors difficult to see against the tracer background [5,6]. It is encouraging to note that 18 F-FDG PET/CT has been used in the diagnosis of bladder cancer through delayed postdiuretic imaging and has exhibited high sensitivity and accuracy in our recent studies [7,8]. However, because of the rarity of urachal carcinoma, the 18 F-FDG PET/CT literature consists only of case reports [9].
In this study, we describe the delayed 18 F-FDG PET/CT findings in urachal adenocarcinomas, which, to our knowledge, is the first series to assess the diagnostic value of delayed 18 F-FDG PET/CT for urachal carcinomas.

Patients.
We retrospectively reviewed all available clinicopathological data for 6 patients with urachal carcinoma who were examined by delayed postdiuretic 18 F-FDG PET/CT and, subsequently, histologically diagnosed by radical resection of urachal carcinoma (n � 5) or biopsy (n � 1) at the Shanghai Jiaotong University-affiliated Ren Ji Hospital from January 2017 to July 2019. Among the 6 patients, 5 patients were treated with radical resection of urachal carcinoma; the remaining one patient was treated with chemotherapy. e study was approved by the institutional review board of the Shanghai Jiaotong Universityaffiliated Ren Ji Hospital and was in accordance with the 2013 revision of the Declaration of Helsinki. e need for informed consent was waived in this study.

Delayed Postdiuretic 18 F-FDG PET/CT Imaging.
Blood glucose levels were measured and found to be less than 140 mg/dL at the time the 18 F-FDG was administered. All patients received an intravenous 3.7 MBq/kg injection of 18 F-FDG after fasting for at least 6 h and resting for 1 h. 18 F-FDG PET/CT scanning from the groin to the skull base was performed using a whole-body scanner (Biograph mCT; Siemens, Erlangen, Germany) (early PET/CT imaging). After early PET/CT imaging, delayed postdiuretic PET/CT imaging was performed after 120 min of early PET/CT imaging. Patients received 20 mg of furosemide by the oral route and an extra oral intake of at least 500 mL water.
Patients were asked to void frequently to reduce the urine physiological uptake of the radiotracer 18 F-FDG. Delayed imaging covered a range of one or two bed positions centered at the location of the bladder. PET images were attenuation-corrected and anatomically correlated with lowdose CT images.
For quantitative analysis, irregular regions of interest were placed over the most intense area of 18 F-FDG uptake on delayed postdiuretic PET/CT imaging.
e SUVmax was calculated as (maximum pixel value with the decaycorrected region-of-interest activity [MBq/mL])/(injected dose [MBq]/body weight [kg]). e PET/CT images were evaluated by two experienced nuclear medicine physicians. e TLR was calculated as the SUVmax of primary tumors/ SUVmax of the liver. e TUR was calculated as the SUVmax of primary tumors/SUVmax of urine (delay).

Statistical Analysis.
e data are presented as mean ± SD. Statistically significant differences between groups were compared using the Mann-Whitney U-test. P < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS, version 13.0 (SPSS Inc.).

Patient Characteristics.
e patient characteristics and delayed 18 F-FDG PET/CT finding are listed in Table 1. ere were 3 males and 3 females with an average age of 48.7 (range 35-71 years). e tumor size averaged 4.3 cm in the largest cross-sectional diameter (range 2.8-7.8 cm). Five cases appeared as solid lesions and one case appeared as mixed cystic-solid lesion. Four cases appeared as a round-like nodule or mass and two cases appeared as irregular lumps. All were adenocarcinomas. Calcifications were radiologically visible in one case. One case (Case 2) had distant metastasis in the peritoneal and bone. In our series, 5 patients (83.3%) presented with hematuria as the first clinical sign, and 1 patient (16.7%) presented with painful pelvic mass as the first clinical sign.

PET Appearance.
e mean SUVmax of urine in the bladder of the early image was 42.9 (range 13.5-91.6), so the SUVmax of lesion cannot be easily detected due to urine interference, especially for the intraluminal portion. On the image of 18F-FDG PET/CT in the delayed phase, the bladder is distended and the SUVmax of urine was very low (mean, 3.5; range 1.8-5.2). So, the lesion can be easily visualized by axial CT and PET, particularly the intraluminal portion of the mass. Diuretic 18F-FDG PET/CT was positive in all patients when compared with normal liver tissues or urine after delayed diuresis.
Of the 6 patients, 2 patients underwent ultrasound examination, 1 patient underwent computed tomography, and 3 patients underwent MRI. ough they all found the primary tumors, they did not find any metastatic lesion. Of the 6 patients, 4 patients underwent radical resection of urachal carcinoma because PET/CT found no lymph node and distant metastasis. Postoperative pathology further confirmed the 18 F-FDG PET/CT results. One patient (Case 1) received chemotherapy after radical resection of urachal carcinoma because 18 F-FDG PET/CT found lung metastases, though 18 F-FDG PET/CT and postoperative pathology both found no lymph node metastasis.
us, 18F-FDG PET/CT had a negative predictive value of 100% (5/5) for predicting lymph node metastasis. One patient (Case 2) only received chemotherapy because PET/CT found peritoneal and skeletal metastases.

Discussion
18 F-FDG PET/CT has been widely used for diagnosis of various malignant tumors [10][11][12]. Unfortunately, 18 F-FDG is not an ideal radiotracer for use in urology because of its urinary elimination [13]. In this study, the potential of delayed postdiuretic 18 F-FDG PET/CT for diagnosing urachal carcinoma was analyzed. To the best of our knowledge, this was the first study to assess the diagnostic value of delayed 18 F-FDG PET/CT in urachal carcinomas.
ough Yang et al. reported a case of urachal carcinoma detected by 18 F-FDG PET/CT, it consists of only one case and delayed postdiuretic 18 F-FDG PET/CT was untaken [9]. So, the SUVmax of urachal carcinoma cannot be easily detected due to urine interference in this case. Several investigators have considered 18 F-FDG PET/CT of no utility in the detection of localized urological malignancies and lymph nodes [14]. e limitation of 18 F-FDG PET/CT has been attributed to the urinary excretion of 18 F-FDG. e pooled activity in the urinary system makes the evaluation of urinary lesions difficult. Catheterization has been proposed to reduce bladder spillover for the evaluation of the pelvic region in several studies. In addition to catheterization, our previous studies showed that washing out the excreted 18 F-FDG could also overcome this limitation in bladder cancer [7,8]. Delayed postdiuretic 18 F-FDG PET/ CT exhibited high sensitivity and accuracy for diagnosing bladder cancer in these studies [7,8]. In this study, we showed that the lesion of urachal carcinomas can be easily visualized by delayed postdiuretic 18 F-FDG PET/CT and the lesion was positive in all patients when compared with normal liver tissues or urine after delayed diuresis. CT and MRI have been used to assess the local extent of urachal carcinomas and the presence of pelvic and visceral metastases [15]. However, they have limitations because they can detect only lymph nodes and distant metastasis that are quite enlarged. CT fails to detect lymph node involvement in up to 40-70% of patients with lymph node metastases [16]. 18 F-FDG PET/CT was, however, more sensitive than conventional CT scan in detecting lymph node metastases based on hypermetabolism of lymph node involvement [17]. In this study, 2 patients underwent ultrasound examination, 1 patient underwent computed tomography, and 3 patients underwent MRI. ough they all found the primary tumors, they did not find any metastatic lesion. 18 F-FDG PET/CT found no lymph node metastasis in 5 cases, and postoperative pathology further confirmed the accuracy.
us, delayed postdiuretic 18F-FDG PET/CT had a negative predictive value of 100% (5/5) for predicting lymph node metastasis in our study. In one patient, radical resection of urachal carcinoma was not performed because PET/CT found peritoneal and skeletal metastases. us, delayed postdiuretic 18 F-FDG PET/CT have the potential to improve clinical decision making and management of urachal carcinomas.
Our study was, in part, limited by its retrospective design and small sample size. Although delayed postdiuretic 18 F-FDG PET/CT may have a good diagnostic performance for urachal carcinoma, further large and prospective studies were needed to confirm our results.

Conclusions
Our results were the first to show the diagnostic value of delayed postdiuretic 18 F-FDG PET/CT in the urachal carcinomas.
ese results may advance the development of noninvasive strategies to improve clinical decision making and management of urachal carcinomas. Further larger and prospective studies that include more clinical samples are needed to confirm the value and efficacy of delayed postdiuretic 18 F-FDG PET/CT in urachal carcinomas.

Data Availability
e data used to support the findings of this study are available from the corresponding author upon request.  Figure 1: (a) Images of a 44-year-old man with urachal carcinoma (Case 3). On the 18 F-FDG PET/CT images, axial CT shows that the spaceoccupying lesion was located in the bladder dome. However, the 18 F-FDG uptake of the lesion cannot be easily detected because of urine interference in the early image (early). (b) On the image of 18 F-FDG PET/CT in the delayed phase, the ureter is distended and the lesion can be easily visualized by axial CT and PET (SUVmax, 58.9) (delay) as the 18 F-FDG uptake of urine in the bladder was very low (SUVmax, 5.2). e patient underwent radical resection of urachal carcinoma, and moderately differentiated adenocarcinoma was confirmed by histopathology.