Chikako Tsumoto

Distinguishing benign from malignant gallbladder wall thickening using FDG-PET.

ObjectiveBecause thickening of the gallbladder wall is observed not only in patients with gallbladder cancer but also in those with benign diseases such as chronic cholecystitis and gallbladder adenomyosis, it is difficult to distinguish between benign and malignant gallbladder wall thickening by conventional techniques of diagnostic imaging such as computed tomography (CT), magnetic resonance imaging (MRI), and abdominal ultrasonography (US). In the present study, we attempted to distinguish between benign and malignant gallbladder wall thickening by means of fluorine- 18-fluorodeoxyglucose (FDG)- Positron emission tomography (PET).MethodsFDG-PET was performed in 12 patients with gallbladder wall thickening detected by CT or US, to determine whether it was benign or malignant. Emission scans were taken, beginning 45 minutes after intravenous administration of FDG, and SUV was calculated as an indicator of glucose metabolism.ResultsOf the 12 patients, 4 showed positive uptake of FDG in the gallbladder wall. Of these 4 patients, 3 had gallbladder cancer. The remaining one, who had chronic cholecystitis, had false-positive findings. The other 8 patients had negative uptake of FDG in the gallbladder wall. Two of these 8 underwent surgical resection, which yielded a diagnosis of chronic cholecystitis. The other 6 patients exhibited no sign of gallbladder malignancy and have been followed without active treatment.ConclusionsFDG-PET appears able to distinguish between benign and malignant gallbladder wall thickening.

Disorder of autonomic nervous system and its vulnerability to external stimulation in functional dyspepsia

To elucidate the role of autonomic nervous system in functional dyspepsia patients, we examined 24-h heart rate variability: the basal levels, responses after lunch, cold pressor and mental arithmetic tests, and the efficacy of an autonomic drug (tofisopam). The high-frequency component (HF: 0.15–0.40 Hz) and the ratio of HF to the low-frequency component (LF: 0.04–0.15 Hz; LF/HF ratio) were used as indicators of parasympathetic and sympathetic autonomic nervous system function. The HF component in the 24-h, daytime, and nighttime was low in 86.7%, 97.8%, and 66.7% of patients (n = 45) and the LF/HF ratio was high in 51.1%, 73.3%, and 26.6% of patients. Gastrointestinal symptom tended to be severe in patients with autonomic nervous system disorder (p = 0.085). The abnormal response in HF component after lunch occurred in 38.2% (13/34) of patients who revealed a greater tendency towards in indigestion score (p = 0.061). Delays in recovery to the basal autonomic nervous system level after stimulus of the cold pressor and the mental arithmetic tests occurred in parts of patients. Tofisopam partially improved autonomic nervous system dysfunction and abdominal pain/indigestion. Imbalanced autonomic nervous system function and vulnerability for recovery from external stimuli were observed in functional dyspepsia patients, which was associated with dyspeptic symptoms.

Regional brain disorders of serotonin neurotransmission are associated with functional dyspepsia.

AIMS To elucidate the role of cerebral serotonin neurotransmission in visceral perception in functional dyspepsia (FD), we observationally examined the regional expression level of the serotonin transporter (SERT) and its correlation with clinical symptoms. MAIN METHODS FD patients (Rome III criteria; N=9, age range: 36-76years) and healthy controls (N=8, age range: 25-61years) participated in this study. Positron emission tomography scanning with [(11)C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([(11)C]DASB), which binds specifically to SERT, was used to quantify the binding potential (BPND) of [(11)C]DASB in the midbrain, thalamus, caudate, putamen, amygdala, and hippocampus with reference to co-registered magnetic resonance images. Clinical symptoms were assessed using the Gastrointestinal Symptoms Rating Scale (GSRS). Self-Rating Depression Scale (SDS), and State-Trait Anxiety Inventory (STAI). KEY FINDINGS BPND of the midbrain (P=0.041) and thalamus (P=0.031) was higher in FD patients than in controls. The BPND values in the midbrain correlated with total GSRS (r=0.663, P=0.004) and abdominal pain (r=0.419, P=0.047) scores. Its values in the thalamus correlated with total GSRS (r=0.423, P=0.044), abdominal pain (r=0.502, P=0.022), and indigestion (r=0.476, P=0.028) scores. Its value in the hippocampus correlated with abdominal pain and state-STAI scores (r=0.528, P=0.017; r=0.428, P=0.043). SIGNIFICANCE Up-regulation of the SERT level in the midbrain and thalamus may underlie the pathogenesis of FD such as abdominal and psychological symptoms via a brain-gut interaction.

Evaluation of diagnostic abilities of Ga-SPECT for head and neck lesions.

ObjectiveSingle-photon emission computed tomography (SPECT) using gallium (Ga) has been frequently used for diagnosing head and neck tumors in patients. Although the usefulness of Ga-SPECT is well known, the degree of the increase in diagnostic ability with Ga-SPECT for head and neck tumors has not been reported. We compared the ability of the planar images of Ga scintigraphy, SPECT images of Ga scintigraphy, and CT images to diagnose head and neck primary tumors and neck metastases.MethodsThe subjects of this study were 167 patients with malignant head/neck lesions. For Ga scintigraphy, Ga-67-citrate (74 MBq) was injected via a cubital vein. Planar and SPECT images were taken 72 h after the Ga-67-citrate injection. The rate of detection of the primary lesions was compared first between SPECT and planar images then between SPECT and CT images. The rate of detection for each stage of disease according to the TNM classification was also analyzed.ResultsThe rate of detection of primary lesions was 50% with planar imaging and 69% with SPECT. And similarly, regarding the rate of detection of lymph node metastases, there was a significant difference between planar imaging and SPECT. The rate of detection of primary lesions was 70% for both CT and SPECT. At T stage, the rates of detection of primary lesions with each imaging technique were 11% with planar imaging and 39% with SPECT, and 22% with CT for stage T1.ConclusionsThis study revealed the marked superiority of SPECT images over planar images in terms of the ability to detect primary tumors and tumor metastasis to cervical lymph nodes. Furthermore, the primary T1 tumor detection rate of SPECT images was higher than that of CT images. On the basis of these results, the concomitant use of SPECT is highly recommended when Ga scintigraphy is performed to check for malignant head/neck tumors.

Detection of local residual tumor after laryngeal cancer treatment using FDG-PET

Objective: Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is sometimes used as a means of follow-up after diagnosis and treatment of cancers of the head and neck region. The present study was undertaken to evaluate the ability of FDG-PET to detect local residual tumor after treatment of laryngeal cancer.Methods: Thirty-six patients with laryngeal cancer underwent FDG-PET before and after initial treatment. Of these patients, 20 received FDG-PET before treatment and 28 received it after treatment. The relationship between standardized uptake values (SUV) and the presence or absence of local residual tumor was investigated by setting the cut-off value of the SUV using the receiver operating characteristics (ROC) curve.Results: When the pre-treatment SUV threshold for laryngeal cancer was set at 7.20, the detection of local residual tumor after treatment using FDG-PET had a sensitivity of 77.78%, specificity of 81.82%, false positive rate of 18.18%, false negative rate of 22.22%, accuracy of 80% and a p value of 0.02. When the post-treatment SUV threshold for the larynx was set at 3.35, the test had a sensitivity of 93.75%, specificity of 91.67%, false positive rate of 8.33%, false negative rate of 6.25%, accuracy of 92.86% and a p value of 0.0001.Conclusions: FDG-PET was found to be useful for determining the presence of local residual tumor after treatment of laryngeal cancer.

Examination of pattern of RI accumulation in thyroid cartilage on bone scintigraphy

ObjectiveIn bone scintigraphy, abnormal RI accumulation in ossified thyroid cartilage is often noted. However, because similar accumulation is also seen in tumor-involved cartilage, distinction between these two lesions is sometimes difficult. We examined the differences in RI accumulation by ossification of the thyroid cartilage and cartilage invasion with anterior, posterior, and oblique views of bone scintigraphy in this study.MethodsThis study included 120 patients (104 men, 16 women; mean age 67.8 ± 9.6 years; range 48–90 years) with laryngeal or lower pharyngeal carcinoma. The patients had exhibited abnormal accumulation of RI on thyroid cartilage on bone scintigraphy between February 1999 and March 2007. We evaluated accumulation of thyroid cartilage in the anterior, posterior, and oblique views on bone scintigraphy. The presence/absence of tumor invasion of the thyroid cartilage was checked by comparing the findings of enhanced computed tomography and magnetic resonance imaging (MRI) as well as evaluating operative records. RI accumulation in thyroid cartilage was divided into four types (diffuse accumulation, intense diffuse accumulation, slight inhomogeneous accumulation, and intense inhomogeneous accumulation).ResultsTumor invasion of thyroid cartilage was noted in 2 of the 42 patients with diffuse accumulation, 1 of the 18 patients with intense diffuse accumulation, 1 of the 38 patients with slight inhomogeneous accumulation, and 17 of 22 patients with intense inhomogeneous accumulation. Because the degree of tumor invasion was highest in cases in which bone scintigraphy revealed intense inhomogeneous accumulation of RI in the thyroid cartilage, we judged this pattern of RI accumulation to be an indicator of tumor invasion. When diagnosis was based on this criterion, positive predictive value, negative predictive value, and accuracy were 77%, 96%, and 93%, respectively (P < 0.0001, Chi-square test).ConclusionsThe findings of this study suggest that ossification of thyroid cartilage can be distinguished from tumor-involved thyroid cartilage on the basis of the pattern of abnormal RI accumulation in the thyroid cartilage in patients with head/neck cancer.

M1279 Overlapped Heartburn/Regurgitation Amplifies Abdominal Pain and Indigestion via Common Central Serotonin Neurotransmission Disorders in Patients With Functional Dyspepsia

Background: Patients with functional dyspepsia (FD) tend to be more depressed and anxious than healthy controls but what comes first is not clear. We hypothesized that psychological morbidity can be secondary to abnormal gastrointestinal afferent signaling. We therefore evaluated depression-like and anxiety-like behaviors and the sensitivity to stress in a previously described rat model of FD. Methods: 10 days old male Sprague-Dawley rats received 0.2 ml of 0.1% iodoacetamide (IA) in 2% sucrose daily by oral gavages for 6 days. Control group received 2% sucrose. At 8-10 weeks of age, sucrose preference test (SPT) and forcedswim test (FST) were used for testing depression-like behavior and elevated plus maze (EPM) and open field test (OFT) were used to test anxiety-like behaviors. Subsequently plasma ACTH, corticosterone and oxytocin levels in response to a minor stressor (subcutaneous saline injection) were measured. RNA was extracted from various brain regions. Results: Rats with neonatal gastric irritation (NGI) showed several abnormalities on the FST as compared with control (Immobility: 32.4± 3.95 vs. 12.95±2.80, climbing: 7.05± 1.18 vs. 18.65 ±1.9 and swimming: 20.6± 3.02 vs. 28.35± 2.1, P 75% of total intake) was decreased in NGI rats (45% versus 80%; p <0.05). No significant change between NGI and control animals was observed in EPM test. On the other hand, OFT showed that the time at center and total distance moved were significantly decreased in NGI rats compared to control rats (16± 4. vs 30±5 and 9182±655 vs 11548± 332, P <0.05). The basal level of plasma corticosterone in NGI rats was significantly higher than that in control rats (3.05±0.74 vs. 1.41±0.25, P<0.05) although stress did not induce a further elevation. Further, while stress did not alter the plasma ACTH and oxytocin concentration in control rats, the hormone levels were significantly increased in stressed NGI rats compared to non-stressed FD rats (49.45±11.42 vs 22.76±2.05 and 14.87±1.50 vs 7.07±0.62, P<0.05). Gene array data showed significant changes in key molecules that modulate stress and depression including 5-HT1A, 5-HT2A, TrkB, NPYr1 and oxytocin. Conclusions: These results suggest that transient gastric irritation in the neonatal period can induce long lasting depressive behavior as well as sensitivity to stress, associated with specific molecular correlates. These findings have major implications for the pathogenesis and treatment of psychological co-morbidity in patients with FD. Thus, gastric hypersensitivity could be a cause rather than an effect of depression.

1098 Central Serotonin Neurotransmission Disorders Correlate with Visceral Perception and Psychological Characteristics in Patients with Functional Dyspepsia

Background& Aims: Visceral perception of functional dyspepsia (FD) is based on the braingut interaction via various neurotransmission pathways. Peripheral or central serotonergic abnormalities are associated with the pathophysiology of functional gastrointestinal disorders or psychiatric depression and anxiety. To examine the roles of the cerebral serotonin (5HT) neurotransmission systems in visceral perception of FD patients, we examined both 5HT transporter (5-HTT) binding potential in the brain and the correlation between differences between patients and controls in 5-HTT binding potential and abdominal symptoms. Methods: Patients with FD diagnosed according to the Rome III criteria (N=9, female: 6, age range 25-61 yrs) were recruited for this study. There were 9 healthy controls (female: 3, age range 36-76 yrs). To measure 5-HTT binding potential with region-of-interest data in areas of the thalamus, putamen, caudate, amygdala, midbrain, and cerebellum (as a reference region), positron emission tomography (PET) with [11C]N,N-dimethyl-2-(2-amino4-cyanophenylthio) benzylamine ([11C]DASB), which binds specifically to 5-HTT, was performed. We used the Multi-linear Reference Tissue Mode method within the standard software package of PMOD Technologies for analysis of [11C]DASB with reference to the co-registered MRI images. Clinical symptoms were evaluated on the Gastrointestinal Symptoms Rating Scale (GSRS) including subscales for abdominal pain and indigestion. Depression and anxiety were evaluated on the Self-Rating Depression Scale and the State-Trait Anxiety Inventory. Results: All scores for abdominal pain, indigestion, depression, and anxiety were higher for FD patients than for controls (p<0.01). In FD patients, the binding potential of [11C]DASB in the midbrain (p=0.001) and amygdala (p=0.065) was higher than in the corresponding areas in controls, while there were no differences between the groups in the thalamus, putamen, or caudate. Binding potential of [11C]DASB in the midbrain was correlated with total GSRS (p=0.018, r=0.572), indigestion (p=0.021, r=0.565), and abdominal pain (p=0.091, r=0.420) scores, while in the amygdala it was correlated with total GSRS (p=0.080, r=0.426), indigestion (p=0.057, r=0.469), depression (p=0.091, r=0.413), and anxiety (p=0.096, r=0.406) scores. Conclusion: These findings suggest that in FD patients there are disorders of central 5-HT neurotransmission, especially in the midbrain and amygdala, which are correlated with their visceral symptoms and psychological characteristics.