The sentinel node concept in prostate cancer: Present reality and future prospects.

A sentinel node (SN) is defined as the first site where cancer cells are carried by lymph flow from a tumor. If this definition (SN concept) correctly reflects the clinical reality, intraoperative SN biopsy would facilitate precise nodal staging. In malignant melanoma, a prolonged survival has been evidenced by a large-scale randomized controlled study. On the contrary, research on SN concept in deeply located cancers including prostate cancer, is still investigative, and no concrete data from clinical trials are yet available. Since 1993, several investigators have demonstrated that the SN concept could be applied in prostate cancer patients as well with high accuracy. Although promising and technically feasible in pre-clinical settings, many hurdles remain to be cleared before clinical application can be recommended. This review addresses the current status and related issues of the SN concept in prostate cancer, and discusses the future directions.

Esophageal hypomotility in systemic sclerosis: close relationship with pulmonary involvement.

PURPOSE: Esophageal motility was assessed in patients with systemic sclerosis (SSc) by scintigraphy and compared with (i) extent of scleroderma, (ii) duration of disease, (iii) index of anti-topoisomerase I antibody (topo I), and (iv) pulmonary involvement. METHODS: A multiple-swallow test was performed in 47 patients with SSc in the supine position with 99mTc-DTPA. A region of interest on the entire esophagus was defined and the retention ratio (RR) was calculated from a time-activity curve. RESULTS: Patients with diffuse scleroderma had higher RRs than those with limited scleroderma (48.8% vs. 30.0%; p < 0.05). There was no correlation between the RRs and the duration of disease. Patients with positive topo I had higher RRs than those who were negative (53.8% vs. 29.7%; p < 0.05). Patients with reduced % diffusion capacity for carbon monoxide (%DLCO) had higher RRs than those with normal %DLCO (40.5% vs. 19.6%; p = 0.03). Patients with reduced % vital capacity (%VC) had higher RRs than those with normal %VC (54.6% vs. 25.0%; p < 0.005). Patients with pulmonary fibrosis had higher RRs than those who were negative (58.5% vs. 20.3%; p < 0.00005). CONCLUSION: Esophageal dysfunction in patients with SSc showed a correlation with the extent of scleroderma, positive topo I, and pulmonary involvement. The RR can be an objective clinical marker for the severity of organ fibrosis.

Prevalence of deep venous thrombosis in the lower limbs and the pelvis and pulmonary embolism in patients with positive antiphospholipid antibodies.

BACKGROUND: Antiphospholipid antibodies (AA) are immunoglobulins that cross-react with phospholipid on cell membrane, and are therefore associated with a hypercoagulable state manifested by arterial/venous thromboses. We aimed to determine the prevalence of deep venous thrombosis in the lower limbs and the pelvic region (DVT) and pulmonary embolism (PE) in patients with positive AA. METHODS: Sixty-six patients (48 female, 18 male) with positive lupus anticoagulant (LA) and/or positive anticardiolipin antibody (aCL) underwent radionuclide (RN) venography with 370 MBq of 99mTc-MAA. Pulmonary perfusion scintigraphy was performed in 58 patients. Fifteen patients had positive LA and positive aCL (LA+/aCL+), 33 patients had positive LA only (LA+/ aCL-) and 18 patients had positive aCL only (LA-/aCL+). 43 patients were diagnosed with primary antiphospholipid syndrome (APS) and 19 were diagnosed with APS associated with SLE. RESULTS: DVT was detected in 21 of 66 patients (32%). Patients with LA+/aCL+ showed higher prevalence of DVT (53%) as compared to LA+/aCL- (27%) and LA-/aCL+ (22%). PE was found in 13 of 58 patients (22%). The prevalence of PE was higher in patients with positive aCL (33% in LA+/aCL+; 36% in LA-/aCL+) than in patients with negative aCL (10%). CONCLUSION: Because of the high prevalence of DVT and PE in patients with AA, RN scintigraphy must be recommended in screening for these clinical troubles. These results indicate that the prevalence of DVT and PE may vary in subgroups of AA.

Long-term postoperative functional evaluation of pylorus preservation in Imanaga pancreatoduodenectomy.

Our purpose was to determine whether pylorus-preservation in the Imanaga (PpPDI) method minimizes postoperative impairment of gastrointestinal function. Nine patients who had undergone PpPDI (postoperative years: 5.7 +/- 2.6) and nine patients who had undergone conventional Imanaga pancreatoduodenectomy (PDI) (postoperative years: 6.8 +/- 2.0) were evaluated for symptoms, nutritional parameters, and physiologic function of the biliary tract and residual stomach using gastric emptying and hepatobiliary scintigraphy. The body weight recovered to 99.3% +/- 3.8% of pre-illness body weight in PpPDI, showing a significantly better recovery than in patients after the PDI procedure (91.0% +/- 6.4%, P < 0.05). The mean gastric emptying half-time (GET1/2) in the upright position after PDI was significantly shorter (42.3 min) than after PpPDI (80.8 min, P < 0.05). Mixture of food with bile was conserved better in the PpPDI group than in the PDI group. In the long term, the pylorus-preserving Imanaga-type procedure minimizes disruption of gastric function and asynchrony between ingested food and bile.

A new examination for both biliary and gastrointestinal function after pancreatobiliary surgery--single-isotope two-day method.

BACKGROUND/AIMS: There are no established tests for both biliary and gastrointestinal function after pancreatobiliary surgery. In this study, mixing of ingested food with bile after long-term postoperative period was evaluated. METHODOLOGY: Sixteen patients having undergone Imanaga pancreatoduodenectomy (postoperative years = 6.2 +/- 2.0) were evaluated concerning physiologic function of biliary tract and residual stomach using gastric emptying and hepatobiliary scintigraphy. RESULTS: At least 24 months after Imanaga pancreatoduodenectomy, postoperative patients had reached 95.8 +/- 4.9% of the pre-illness bodyweight. Gastric emptying half-time (GET1/2) ranged from 9-147 min (mean: 60.6 +/- 35.0). The time of bile excretion from liver to jejunum ranged from 5-45 min (mean: 11.3 +/- 7.8). Asynchrony time ranged from -5-40 min (mean: 11.3 +/- 7.8). There was no significant correlation between GET1/2 and recovery of bodyweight (r = -0.042, P = 0.8809). Similarly, there was no significant correlation between the time of bile excretion and recovery of bodyweight (r = 0.042, P = 0.8791). On the other hand, asynchrony time had a significant inverse correlation with recovery of bodyweight (r = -0.590, P = 0.0146). CONCLUSIONS: Single-isotope two-day method is an original and useful technique to evaluate biliary and gastrointestinal physiologic function after long-term postoperative period.

Simple scintigraphic parameters with Tc-99m galactosyl human serum albumin for clinical staging of chronic hepatocellular dysfunction.

Technetium-99m labeled diethylenetriaminepentaacetic acid (DTPA)-galactosyl human serum albumin (GSA) has been used for hepatocellular functional evaluation. This study proposed new and simple parameters to overcome the limitations of conventional parameters, and they were applied to the clinical staging of chronic liver dysfunction. The study group consisted of 93 patients including 81 with liver dysfunction and 12 control patients. In addition to the two conventional parameters, namely, receptor index (LHL15 = liver count divided by the sum of liver and heart counts at 15 minutes) and clearance index (HH15 = heart count at 15 minutes divided by the heart count at 3 minutes), 6 new parameters for Tc-99m GSA uptake and clearance were generated. The conventional receptor index of LHL15 showed a large variation depending on the size of region of interest (ROI) over the heart. The LHL15 normalized by the ROI size (nLHL15) showed more stable data and a better separation of mild liver dysfunction. A hyperbolic relationship between the LHL15 and HH 15 changed to a linear relationship by using the nLHL15 index. The combination of the liver to heart average count ratio at 15 minutes (LH 15) and T-half (minute) of the heart count also could differentiate each stage well. In conclusion, the use of the ROI-area normalized nLHL is recommended instead of the conventional LHL15. The indices of LH15 and T-half could be alternatively used as practical parameters for clinical staging in liver function.

Discrepancy between blood flow and muscarinic receptor distribution in rat brain after middle cerebral artery occlusion.

To clarify whether muscarinic acetylcholine receptor (mAChR) binding can be a viable muscarinic neuronal marker which provides therapeutic information different from perfusional information in global brain, we evaluated the discrepancy between the distribution of cerebral blood flow (CBF), mAChR and its five subtypes of messenger ribonucleic acid (mRNA) in the acute (n=9) and chronic (n=8) phases of a middle cerebral artery (MCA) occlusion model and in sham-operated controls (n=6). In the acute phase, regional CBF was markedly reduced in the MCA territory, whereas mAChR was not reduced and the mRNA was reduced only slightly. In the chronic phase, mAChR was reduced markedly in the infarcted lesion and the mRNA was also reduced. The mAChR was slightly reduced in the ipsilateral substantia nigra and pontine nucleus because of remote effects; however, regional CBF in the substantia nigra was slightly increased and did not change in the pontine nucleus. The discrepancy between CBF and mAChR was clarified, and the tendency toward a reduction in mRNA in the acute ischaemic region without a reduction in mAChR suggested the presence of cholinergic neurons which were viable but hypometabolic. It is concluded that mAChR imaging may be of value for the assessment of the viable cholinergic neuron density in vivo.

Intense Ga-67 uptake in adenosquamous carcinoma of the pancreas.

Gallium-67 citrate (Ga-67) scintigraphy was performed in a patient with adenosquamous carcinoma of the pancreas. Intense and homogeneous uptake was observed in the tumor. Few reports have dealt with Ga-67 findings in pancreatic cancers. Ga-67 uptake in the tumor was assumed to be due to accumulation in the component of squamous cell carcinoma. This case suggested that Ga-67 citrate scintigraphy may be useful in detecting adenosquamous carcinoma of the pancreas. To our knowledge, no report has described findings of Ga-67 citrate scintigraphy of adenosquamous carcinoma of the pancreas. Radiologists should remember adenosquamous carcinoma of the pancreas when encountering such scintigraphic findings.

Inguinoscrotal lymphatic reflux detected by lymphoscintigraphy.

We performed lymphoscintigraphy with 99mTc-human serum albumin in a case of suspected lymphedema of the right leg after inguinal lymph node dissection. Dermal backflow of the leg and lymphocele at the inguinal chain were observed, and lymphatic reflux into the scrotum was also delineated. The scintigraphy could demonstrate a persistent lymphatic problem under conservative treatment, and could lead the physician to conduct surgical treatment. Scintigraphic demonstration of the inguinoscrotal lymphatic reflux has not been previously reported.

Synthesis of radioiodinated analogs of 2-(4-phenylpiperidino)cyclohexanol (vesamicol) as vesamicol-like agent.

Three iodovesamicol analogs, iodinated at the ortho, meta, and para positions of the 4-phenylpiperidine moiety, were synthesized and labeled with 125I by isotopic exchange reaction. Their potencies as a vesamicol-like drug were evaluated with competitive inhibition studies using (-)[3H]vesamicol. The radiochemical yields were 40-85%, the radiochemical purities exceeded 95% and their specific activities were 370-740 GBq/mmol. The descending order of binding affinity of the tested compounds against the vesamicol receptor was m-iodovesamicol > o-iodovesamicol > p-iodovesamicol. The receptor binding affinity of m-iodovesamicol (IC50 = 133 nM) was comparable with that of vesamicol (IC50 = 109 nM). Therefore, the meta position of the 4-phenylpiperidinyl fragment of vesamicol was the optimum site for iodination, and radioiodinated m-iodovesamicol may serve as a useful radiopharmaceutical for in vitro and in vivo studies of presynaptic cholinergic neurons in rats.

Comparative SPECT study of stroke using Tc-99m ECD, I-123 IMP, and Tc-99m HMPAO.

Brain perfusion SPECT imaging using Tc-99m ethyl cysteinate dimer (ECD) was carried out in 12 patients with chronic cerebrovascular disease. The sensitivity of lesion detection and lesion-to-normal tissue contrast was compared with those of I-123 IMP and Tc-99m HMPAO. Eight patients underwent all three studies and the remaining four patients had Tc-99m ECD and I-123 IMP scans. The sensitivity of lesion detection and lesion contrast was analyzed quantitatively using an asymmetric index determined by the equation: 100 x [right - left[/(right + left). In the cerebral cortex, cerebellum, and white matter, I-123 IMP showed higher lesion sensitivity than Tc-99m ECD and Tc-99m HMPAO. In the striatum and thalamus, Tc-99m ECD and I-123 IMP showed higher lesion sensitivity than Tc-99m HMPAO. I-123 IMP showed the highest lesion contrast in cerebral cortex and cerebellum, whereas Tc-99m ECD showed the highest contrast in thalamus and striatum. In all regions, Tc-99m ECD showed higher lesion contrast than Tc-99m HMPAO. These results suggest regional variation in the sensitivity of lesion detection and lesion contrast of Tc-99m ECD compared to I-123 IMP, and the superiority of Tc-99m ECD to Tc-99m HMPAO.

Acetazolamide effect on vascular response in areas with diaschisis as measured by Tc-99m HMPAO brain SPECT.

The effects of acetazolamide (Diamox) on vascular response were investigated in areas with intrahemispheric thalamic diaschisis and crossed cerebellar diaschisis using consecutive Tc-99m HMPAO brain SPECT studies before and after Diamox administration. All six patients with thalamic diaschisis and five of eight patients with crossed cerebellar diaschisis at baseline showed significantly augmented perfusion after Diamox administration in the affected thalamus and cerebellum compared with that in the contralateral unaffected areas. These results suggest more dilatation of the arterioles in areas with diaschisis after Diamox administration than in areas without diaschisis. Diamox may produce relative luxury perfusion in areas with diaschisis.

Tc-99m HMPAO SPECT analysis of neuroleptic effects on regional brain function.

This report describes a new approach to the evaluation of neuroleptic effects on regional brain function. Using Tc-99m HMPAO SPECT imaging, consecutive brain perfusion studies before and after acute haloperidol administration were performed on three schizophrenic patients and two normal volunteers. The antipsychotic drug ameliorated the hypoactivity in the frontal lobe and suppressed the hyperactivity in the temporo-occipito-parietal lobe selectively in the dominant hemisphere in the schizophrenic patients. It did not exert a significant influence on the brain perfusion pattern in normal volunteers. This nuclear medicine technique seems to be useful for the evaluation of drug effects in psychiatric diseases.

SPECT evaluation of brain perfusion reserve by the acetazolamide test using Tc-99m HMPAO.

This report describes a new approach to the evaluation of brain perfusion reserve using Tc-99m HMPAO SPECT. Consecutive brain Tc-99m HMPAO SPECT studies before and after acetazolamide (Diamox) administration were performed within 30 minutes on 19 patients with significant vascular occlusive lesions. Thirteen patients showed decreased perfusion reserve and four patients maintained perfusion reserve in the affected vascular territories after Diamox administration, providing additional information to baseline Tc-99m HMPAO SPECT in 17 (89%) patients. Although flow augmentation post-Diamox was underestimated, possibly due to the nonproportionality of Tc-99m HMPAO activity to true blood flow, significant changes in the brain perfusion pattern were both visually and quantitatively determined using an image subtraction technique. This consecutive Tc-99m HMPAO SPECT technique seems to be of practical use for the evaluation of brain perfusion reserve and for the improvement of the sensitivity of detecting pathologic areas.

[Evaluation of brain perfusion SPECT imaging using 99mTc-ECD].

Fundamental and clinical evaluation was performed on 99mTc-ECD, a new agent for brain perfusion SPECT. Radiochemical purity reaches a plateau of approximately 98% at 30 min after reconstitution and remains stable up to 24 hours later. A biodistribution study showed approximately 5% injected dose in the brain, very slow brain washout of 5.6% per hour on the average, and rapid washout from the other organ mainly through the urinary system. Brain ECD distribution was determined within 2 min postinjection and remained stable for up to 1 hour. Three hours later, slight but significant changes in brain distribution were observed, that were relative reduction of cerebral cortical activity and gray to white matter activity ratio, and relative elevation of white matter and thalamic activities. Comparative studies of ECD images with IMP and HMPAO images revealed that radioactivity contrast between affected and unaffected areas was less prominent in ECD than in IMP in cerebral and cerebellar cortical lesions, more prominent in ECD than in IMP in striatal and thalamic lesions, and somewhat more prominent in ECD than in HMPAO in both lesions. Imaging around 1 hour postinjection seems to be more appropriate than immediate postinjection imaging because of the clearance of the extracranial radioactivity and somewhat better radioactivity contrast between affected and unaffected areas.

[Fundamental study on nuclear medicine imaging of cholinergic innervation in the brain: changes of neurotransmitter and receptor in animal model of Alzheimer's disease].

A fundamental study was performed on the nuclear medicine imaging of cholinergic innervation in the brain. In a cholinergic denervation model prepared by producing an unilateral basal forebrain lesion in the rat, which is reported to be one of animal models of Alzheimer's disease, quantitative determination of acetylcholine in parietal cortices revealed statistically significant 31% decrease on an average in the ipsilateral side relative to the contralateral side to the lesion. In vitro receptor autoradiography showed no significant differences in total, M1 and M2 muscarinic acetylcholine receptors between the ipsilateral and contralateral cortices to the lesion. Simultaneous mapping of presynaptic cholinergic innervation using 3H-2-(4-phenylpiperidino) cyclohexanol (AH5183) demonstrated significant 14% decrease of AH5183 binding on an average in the ipsilateral relative to the contralateral fronto-parieto-temporal cortices to the lesion. These results suggest that AH5183 is a promising ligand for mapping cholinergic innervation in nuclear medicine imaging.

Tc-99m HMPAO brain perfusion tomography atlas using a high resolution SPECT system.

Excellent SPECT images of brain perfusion with Tc-99m HMPAO were obtained by the use of a three-head rotating gamma camera SPECT system with high resolution (FWHM 7mm) in a normal volunteer. These images should be clinically effective for evaluating various neurologic disorders. Transverse, coronal, and sagittal sectional HMPAO-SPECT images are correlated with corresponding brain MRI images of the same normal volunteer in this atlas.

[Brain perfusion SPECT imaging before and during the acetazolamide test using 99mTc-HMPAO].

A new method using brain perfusion 99mTc-HMPAO SPECT imaging was developed for evaluating cerebral perfusion reserve by the acetazolamide test with a short period. The first SPECT study was carried out for 13.5 min to obtain SPECT images at the resting state after 3 min postinjection of 555 MBq (15 mCi) of 99mTc-HMPAO. At the same time as the start of the first SPECT study, 1 g of acetazolamide was intravenously injected. Immediately after the stop of the 1st SPECT study, 925 MBq (25 mCi) of 99mTc-HMPAO from the same vial as in the first study was additionally injected. Three minutes later the second SPECT study was carried out for 10 min. After reconstruction the tomographic images in the first study were subtracted from the images in the second study to obtain those during the acetazolamide test after correction of the time differences in data acquisition between the two studies. This subtraction technique gives independent brain perfusion SPECT images before and during the acetazolamide test. Besides, the regional flow changes during the test were quantitatively analyzed. In conclusion this method seems to be practically useful for evaluating regional brain perfusion before and during drug treatments as a consecutive study with a short period of approximately 30 min.