Diffusion-weighted MRI, 11C-choline PET/CT, and 18F-FDG PET/CT for predicting the Gleason score in prostate cancer.

OBJECTIVE: To evaluate diffusion-weighted magnetic resonance imaging (DWI), 11C-choline positron emission tomography (PET), and fluorine-18-fluorodeoxyglucose (18F-FDG) PET for predicting Gleason score in prostate cancer patients. SUBJECTS AND METHODS: The study cohort included 11 patients with biopsy-proven prostate cancer who underwent DWI, 11C-choline PET, and 18F-FDG PET examinations before treatment. The correlations of Gleason score with those findings were determined using Spearman's test. Multi-technique imaging performance for separating higher Gleason score (≥8) cases was also examined. RESULTS: Both diffusion coefficient (ADC) map and 11C-choline PET/computed tomography (CT) findings showed prostate cancer in all 11 patients, while 18F-FDG PET/CT was only successful in 6 (54.5%) cases, thus no further evaluations of that modality were performed. A moderately negative correlation was observed between Gleason score and ADC value for the primary tumor shown by DWI, though the difference was not significant (r=-0.49, P=0.13). In contrast, a strongly significant positive correlation was observed between Gleason score and maximum standardized uptake value (SUVmax) for the primary tumor in 11C-choline PET findings (r=0.85, P=0.0010). Sensitivity, specificity, and accuracy for separating higher (≥8) from lower (≤7) Gleason score were 87.5%, 33.3%, and 72.7%, respectively, with a best cut-off value of 0.78 for ADC map, and 87.5%, 100%, and 90.9%, respectively, with a best cut-off value of 6.0 for 11C-choline PET. CONCLUSION: Carbon-11-choline PET was found have a greater correlation with Gleason score than DWI and is considered to be more useful to predict a higher score in patients with prostate cancer. Fluorine-18-FDG PET was limited because of low sensitivity.

Evaluation of Treatment Response in Prostate Cancer and Renal Cell Carcinoma Patients Using 11C-choline PET/CT Findings.

We investigated the effectiveness of 11C-choline-positron emission tomography/computed tomography (PET/CT) for evaluating treatment response in patients with prostate cancer or renal cell carcinoma. We performed 34 11C-choline PET/CT scans before/after a combined total of 17 courses of treatment in 6 patients with prostate cancer and 2 with renal cell carcinoma. The 17 treatments including hormonal therapy, radiotherapy, chemotherapy, radium-223, molecular target therapy, radiofrequency ablation, transcatheter arterial embolization, and cancer immunotherapy yielded 1 (5.9%) complete metabolic response (CMR), 3 (17.6%) partial metabolic responses (PMRs), 2 (11.8%) stable metabolic diseases (SMDs), and 11 (64.7%) progressive metabolic diseases (PMDs). Target lesions were observed in bone (n=14), lymph nodes (n=5), lung (n=2), prostate (n=2), and pleura (n=1), with CMR in 4, PMR in 10, SMD in 8 and PMD in 2 lesions. SUVmax values of the target lesions before and after treatment were 7.87±2.67 and 5.29±3.98, respectively, for a mean reduction of -35.4±43.6%. The response for the 8 prostate cancer-treatment courses was PMD, which correlated well with changes in serum prostatic specific antigen (PSA) (7 of 8 cases showed increased PSA). 11C-choline-PET/CT may be an effective tool for detecting viable residual tumors and evaluating treatment response in prostate cancer and renal cell carcinoma patients.

Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer.

We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men.

[The Usefulness of 11C-Choline PET/CT for Detecting Metastasis and Treatment Monitoring of Renal Cell Carcinoma : Report of Two Cases].

Although fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been widely used as a powerful tool in clinical oncologic imaging, its application in urological malignancies is limited. Recently, choline PET/CT has been successfully used for prostate cancer restaging. Here, we report the utility of choline PET/CT for the detection and monitoring of metastatic disease in two cases of renal cell carcinoma (RCC). A 53-year-old woman and a 45-year-old woman underwent FDG and choline PET/CT for evaluation of metastatic lesions in lymph nodes and bone following left and right RCC, respectively, and choline PET/CT demonstrated significantly higher uptake when compared with FDGPET/CT in both cases. Choline PET/CT accurately reflected the remission and progression of diseases in their clinical course, indicating that choline PET/CT could be a useful imaging modality in metastatic RCC.

Enhancement of death receptor 4-mediated apoptosis and cytotoxicity in renal cell carcinoma cells by anisomycin.

Renal cell carcinoma (RCC) is one of the most drug-resistant malignancies, and an effective therapy is lacking for metastatic RCC. Anisomycin is known to inhibit protein synthesis and induce ribotoxic stress. The aim of this study was to explore whether anisomycin enhances the cytotoxic effects of mapatumumab, a human agonistic monoclonal antibody specific for death receptor 4 (DR4), in human RCC cells. We examined the cytotoxicity of anisomycin alone and in combination with mapatumumab in human RCC cell lines and primary RCC cell cultures. RCC cells treated with anisomycin showed cytotoxicity in a dose-dependent manner. Anisomyin in combination with mapatumumab showed a synergistic effect not only in two human RCC cell lines but also in five primary RCC cell cultures. The synergy between anisomycin and mapatumumab for cytotoxicity was also observed for apoptosis. Interestingly, anisomycin significantly increased DR4 expression at both the mRNA and the protein level. Furthermore, the combination-induced cytotoxicity was significantly suppressed by a human recombinant DR4:Fc chimeric protein. The combination of anisomycin and mapatumumab also enhanced the activity of caspases 8 and 3, the downstream molecules of death receptors. These findings indicate that anisomycin sensitizes RCC cells to DR4-mediated apoptosis through the induction of DR4, suggesting that combinational treatment with anisomycin and mapatumumab might represent a novel therapeutic strategy for the treatment of RCC.

Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p < 0.0001, respectively). 11C-choline PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p < 0.0001). According to the CT morphological type, the visualization rates of 11C-choline-PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

11C-Choline positive but 18F-FDG negative pancreatic metastasis from renal cell carcinoma on PET.

Choline is a new PET tracer, which uptake may occur via a choline-specific transporter protein and be accelerated during the proliferation of tumor cells. We report a 61-year-old woman with a metastatic pancreatic tumor from renal cell carcinoma, measuring 35×40 mm. PET scans demonstrated accumulation of 11C-choline in the metastatic pancreatic tumor, but no accumulation of 18F-FDG. Choline PET/CT may play a useful and complementary imaging modality, especially when FDG-PET/CT does not show expected findings or when the evaluation of tumor viability is needed, in patients with renal cell carcinoma.

[An Adult Case of Transperineal Repair of Congenital Rectourethral Fistula Using Gracilis Muscle Flap Interposition].

A man in his 50s was referred to our hospital after recurrent severe urinary tract infection. He had undergone anoplasty for anorectal malformation during early infancy. He noticed urinary leakage from the anus for a long time. Under diagnosis of congenital rectourethral fistula, we performed fistula closure. The fistula was transsected via transperineal incision and each stump was closed. A gracilis muscle flap approximately 30 cm long was harvested from the left thigh, brought into the deepest part between the separated rectum and urethra through a subcutaneous tunnel and fixed there. The urinary leakage from the anus disappeared, and the infection resolved. Application of gracilis muscle flap for congenital diseases is rare, but was useful in the present case.

[Leiomyosarcoma of the inferior vena cava: a case report and review].

A 37-year-old woman with an incidentally found abdominal mass was referred to our hospital. A fixed, non-tender mass was palpated in the right upper quadrum of her abdomen. There was no elevation of tumor markers. Computed tomography revealed a mass extending from the hepatic vein level to renal hilar level. The tumor completely obstructed the inferior vena cava (IVC). T1-weighted magnetic resonance imaging (MRI) showed that the mass was isointense with muscles. T2-weighted MRI image with contrast medium demonstrated collateral circulation. Upon diagnosis of the IVC tumor, we removed the right kidney and the tumor en bloc without reconstructing IVC. The tumor diameter was 11.6 × 5.5 × 4.7 cm. Pathological examination established a diagnosis of IVC leiomyosarcoma. She is alive without sign of recurrence after operation for seven months. There were 143 reports of IVC leiomyosarcoma in Japan. In 31% of them, IVC was not reconstructed.

[The safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week off) for treatment of metastatic renal cell carcinoma].

We prospectively investigated the safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week off) in 24 patients (22 males, 2 females ; age range 39-86 years, median 64 years) with metastatic renal cell carcinoma (RCC). During the observation period (3-62 weeks, median 21 weeks), thrombocytopenia was seen in 13 (54.2%), leukopenia in 11 (45.8%), hand-foot syndrome in 5 (20.8%), hypertension in 4 (16.7%), and hypothyroidism in 3 (12.5%) patients, while grade 3 or higher adverse events were found in 4 (16.7%), 1 (4.2%), 1 (4.2%), 2 (8.3%), and 0 patients, respectively. Of the 21 patients evaluable for response, 5 (23. 8%) showed partial response, 8 (38.1%) stable disease, and 8 (38.1%) progressive disease. This new modified regimen may lead to a reduction in adverse events for treatment of patients with metastatic RCC as a substitute for the standard dosing regimen of sunitinib.

[Assessment of oral health using the general oral health assessment index in patients with overactive bladder].

Patients administered anti-cholinergic agents, as first-line therapy for an overactive bladder (OAB) are often unable to continue medical treatment because of dry mouth. We assessed oral health in patients with OAB using the General Oral Health Assessment Index (GOHAI), an oral health-related quality of life questionnaire. We investigated 75 patients with OAB who were receiving continuous administration of anti-cholinergic agents. The OAB symptom score, as well as GOHAI and our original dry mouse score were determined by self-administered questionnaires. The mean age of the subjects was 70.9±10.2 years, the median period of anti-cholinergic agent use was 20 (1-116) months and the mean OAB symptom score was 6.3±3.1. The GOHAI score for all patients was 51.9±8.4 and not significantly different from the national normal value (p＝0.22). On the other hand, the score in patients with a severely dry mouth was 49.2±8.6, which was worse than the national normal value (p＝0.04). The psychosocial functioning score in patients with a severely dry mouth was significantly lower than in those with a slightly dry mouth (p＝0.02). Our results indicate that dry mouth in patients with OAB is significantly associated with worsening of oral health. GOHAI is useful as a screening test to assess the quality of life in patients with OAB.

[Impacted ureteral stents with cystine encrustation in cystinuric patients : report of two cases].

A 23-year-old man and a 62-year-old man suffering from cystinuria underwent extracorporeal shock wave lithotripsy (ESWL) for right renal stone and left ureteral stone, respectively. They had double-J stents placed before ESWL, but since attempts to retrieve the stents were unsuccessful due to encrustation, they were referred to our clinic. Multimodal endourologic and open approaches including ESWL, transurethral ureterolithotripsy, and pyelolithotomy were required to render them stent- and stone-free. The guidelines do not recommend routine stenting before ESWL ; therefore, the indication and duration of indwelling stents should be minimized. Multimodal options including not only ESWL and endoscopic surgery but also open surgery, should be attempted for the management of encrusted stents. Close monitoring and follow up are important to the prevent complications of ureteral stents.

[Unclassified renal cell carcinoma accompanying pyonephrosis: a case report].

A 73-year-old male, admitted to a local hospital because of fever and consciousness disturbance, was referred to our institute. He had a history of long-term steroid administration and diabetes mellitus. Under diagnosis of severe right pyonephrosis associated with severe inflammatory response syndrome as well as disseminated intravascular coagulopathy, he was transferred to our hospital. Computed tomography and magnetic resonance imaging showed a mass 5 cm in diameter at the right ureteropelvic junction and lymph node swelling at the renal hilum, suggesting obstructive pyonephrosis by a malignant tumor such as renal pelvic cancer. Since the patient failed to respond to conservative medical treatment including polymyxin B hemoperfusion, hemodialysis, and antimicrobials, we performed right nephrectomy. Histopathological examination demonstrated that the tumor obstructing the pelvis arose from the parenchyme under the muscle layer, and was diagnosed as unclassified renal cell carcinoma while the renal pelvic epithelium was normal. Although his general condition and laboratory data transiently improved after nephrectomy, he died of carcinomatous peritonitis 30 days postoperatively. We advocate that, in the case of pyonephrosis with a lesion highly suspected to be an infiltrating neoplasm, nephrectomy is justified as first choice to control the septic condition.

Imaging of renal cell carcinoma in patients with acquired cystic disease of the kidney: comparison 11C-choline and FDG PET/CT with dynamic contrast-enhanced CT.

PURPOSE: To evaluate renal cell carcinoma (RCC) findings in acquired cystic disease of the kidney (ACDK) shown by 11C-choline and FDG PET/CT, and contrast-enhanced CT. MATERIALS AND METHODS: Six ACDK patients with 7 RCCs underwent 11C-choline and FDG PET/CT, and contrast-enhanced CT before nephrectomy. Findings obtained with 3 imagings were evaluated and sensitivity detecting RCC was compared using 3-point grading scale (negative, equivocal, positive). The equivocal scale used for SUVmax ranged from 2.0 to 3.0 for PET/CT and a peak enhancement value ranging from 20 to 30 HU was used for CT. RESULT: The histopathologic subtypes of 7 RCCs were clear-cell (n = 4) and ACD-associated RCC (n = 3). The negative/equivocal/positive grading results were 0/0/7 for 11C-choline-PET/CT, 0/3/4 for FDG-PET/CT, and 2/2/3 for CT. Three equivocal cases by FDG-PET/CT were 2 clear-cell RCCs and 1 ACD-associated RCC. CT of 3 ACD-associated RCCs showed negativity for 2 and equivocality for 1. Sensitivity defining equivocal interpretation as negative for 11C-choline-PET/CT, FDG-PET/CT, and CT was 100% (7/7), 57.1% (4/7), and 42.9% (3/7). CONCLUSION: 11C-choline-PET/CT was more sensitive to detect RCC in ACDK as compared to FDG-PET/CT and contrast-enhanced CT in our series. FDG-PET/CT may be limited for detecting clear-cell RCC, while CT may have difficulty with detection of ACD-associated RCC.

The Potential Use of 11C-Choline Positron Emission Tomography/Computed Tomography to Monitor the Treatment Effects of Radium-223 in a Patient with Prostate Cancer.

We report here about a 59-year-old man with bone metastatic castration-resistant prostate cancer and biochemical progression, who underwent radium-223 (Ra-223) therapy, following previous treatment failure. Treatment response of osseous metastases was assessed with three 11C-choline positron emission tomography/computed tomography (PET/CT) scans at baseline, after three cycles for early monitoring, as well as after six cycles of radium-223 therapy. Pretreatment 11C-choline PET/CT showed multiple areas of increased focal activity in multiple cervical, thoracic, and lumbar vertebrae as well as in both ribs, right ileum, and left ischium. Second 11C-choline PET/CT after three cycles showed increasing tumor activity in the existing lesions and the new uptake spots of thoracic spine, both ribs and left ileum. Third 11C-choline PET/CT at the end of the therapy showed further progression with new lesions of thoratic spine, sacrum, right rib, and right ileum. In this case, 11C-choline PET/CT after three cycles for early monitoring could predict the therapeutic response to Ra-223.

Comparison of 11C-choline Positron Emission Tomography/Computed Tomography (PET/CT) and Conventional Imaging for Detection of Recurrent Prostate Cancer.

We aimed to compare 11C-choline positron emission tomography/computed tomography (PET/CT) with conventional imaging, including pelvic magnetic resonance imaging (MRI), contrast-enhanced chest, abdomen, and pelvic computed tomography (CT), and bone scintigraphy, for prostate cancer restaging. Thirty patients (median prostate-specific antigen [PSA: 11.8 ng/mL]) with suspected recurrent prostate cancer following definitive treatment underwent 11C-choline PET/CT and conventional imaging, including pelvic MRI, contrast-enhanced chest, abdomen, and pelvic CT, and bone scintigraphy. The results were compared with regard to patient- and lesion-based diagnostic performance for local recurrence, and for lymph node and bony metastases using receiver operating characteristic (ROC) analysis and McNemar's test. Documented local recurrence and node and bony metastases were present in 11 (36.7%), 10 (33.3%), and 17 (56.7%) cases, respectively, of the enrolled patients. Patient-based sensitivity / specificity / accuracy / area under the ROC curve for 11C-choline-PET/CT for diagnosing local recurrence were 90.9% / 94.7% / 93.3% / 0.975 and for conventional imaging were 90.9% / 100% / 96.7% / 1.0. Those who underwent 11C-choline-PET/CT for node metastasis were 90.0% / 95.0% / 93.3% / 0.925 and for conventional imaging were 70.0% / 95.0% / 86.7% / 0.905. Those who underwent 11C-choline-PET/CT for bone metastasis were 94.1% / 92.3% / 93.3% / 0.991 and who underwent conventional imaging were 94.1% / 84.6% / 90.0% / 0.982. No significant differences were observed among them. The lesion-based detection rate of 11C-choline PET/CT for local recurrences and node and bone metastases as compared to conventional imaging was 92.9% (13/14) vs. 92.9% (13/14); 87.1% (27/31) vs. 54.8% (17/31); and 96.9% (219/226) vs. 90.3% (204/226) respectively, with significant differences noted for detection of node and bone lesions (p=0.0044 and p=0.00030, respectively). 11C-choline-PET/CT is more accurate in the detection of recurrent prostate cancer nodes and bony metastatic lesions compared to conventional imaging and has the advantage of restaging the disease in a single step.

Tiny Obturator Node Metastasis from Prostate Cancer Not Shown by FDG-PET/CT, CT, or MRI Detected by 11C-Choline PET/CT.

We report a 65-year-old male with histopathologically proven prostate cancer and multiple pelvic node metastases using a robotic-assisted radical prostatectomy procedure plus extended pelvic lymph node dissection. Positron emission tomography (PET) scan findings demonstrated a moderate accumulation of 11C-choline in a metastatic left obturator node sized 8 × 8 mm, though only a faint uptake of fluorodeoxyglucose (FDG) was noted. 11C-choline PET/computed tomography (CT) may be useful for the diagnosis of a tiny metastatic lymph node not demonstrated by CT, magnetic resonance imaging, or FDG-PET/CT and to determine the need for an extended pelvic lymph node dissection.

Diagnostic performance of 11C-choline PET/CT and FDG PET/CT for staging and restaging of renal cell cancer.

PURPOSE: To compare findings obtained with 11C-choline and FDG PET/CT scanning for renal cell carcinoma staging and restaging. MATERIALS AND METHODS: Twenty-eight renal cell carcinoma patients whose histological subtype was clear cell type in 26 and papillary type in 2, while Fuhrman nuclear grade was G1,2 in 16 and G3,4 in 12, underwent both 11C-choline and FDG PET/CT examinations before (n = 10) and/or after (n = 18) treatment, then those scanning modalities were compared in regard to patient- and lesion-based diagnostic performance using 5 grading scores. Final diagnosis in each case was obtained based on histopathology, conventional radiological imaging, and clinical follow-up findings. The differences between 11C-choline and FDG PET/CT findings were evaluated using receiver-operating-characteristic (ROC) analysis and a McNemar test. RESULTS: Patient-based sensitivity, specificity, positive predictive, negative predictive, accuracy, and area under the ROC curve (AUC) values for 11C-choline PET/CT for staging and restaging were 88.0% (22/25), 66.7% (2/3), 95.7% (22/23), 40.0% (2/5), 85.7% (24/28), and 0.887, respectively, while those for FDG-PET/CT were 56.0% (14/25), 66.7% (2/3), 93.3% (14/15), 15.4% (2/13), 57.1% (16/28), and 0.647, respectively. Sensitivity, accuracy, and AUC were significantly different (p = 0.013, p = 0.013, p = 0.012, respectively). Among the 120 lesions, those with kidney, lung, lymph node, bone, pancreas, venous tumor thrombosis, adrenal gland, liver, or skin localization numbered 15, 64, 16, 13, 4, 3, 2, 2, and 1, respectively. For all 120 lesions, 75 (62.5%) and 47 (39.2%) were detected by 11C-choline and FDG PET/CT, respectively (p < 0.0001). CONCLUSION: For staging and restaging of renal cell carcinoma patients, 11C-choline-PET/CT is significantly more useful than FDG-PET/CT.

11C-Choline-Avid but 18F-FDG-Nonavid Prostate Cancer with Lymph Node Metastases on Positron Emission Tomography.

Choline is a new positron emission tomography (PET) tracer useful for detection of prostate cancer and metastatic lesions. We report a 70-year-old man with prostate cancer and multiple abdominal, pelvic, and inguinal node metastases. PET scans demonstrated accumulation of 11C-choline in the primary tumor and lymph node metastases but no accumulation of 18F-FDG. Choline PET/computed tomography may be useful for diagnosis of advanced prostate cancer with suspected metastatic lesions and treatment planning.