Accumulation of [<Superscript>11</Superscript>C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer

Carbon-11 acetate positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of prostate cancer. However, no detailed analysis has yet been carried out on the physiological accumulation of [(11)C]acetate in the prostate. The purpose of this study was to elucidate the physiological accumulation of [(11)C]acetate in the prostate using dynamic PET. The study included 30 subjects without prostate cancer [21 with normal prostate and nine with benign prostatic hyperplasia (BPH)] and six patients with prostate cancer. A dynamic PET study was performed for 20 min after intravenous administration of 555 MBq of [(11)C]acetate. The standardised uptake value (SUV) at 16-20 min post tracer administration and the early-to-late-activity ratio of the SUV (E/L ratio), which was determined by dividing the SUV(6-10 min) by the SUV(16-20min), were calculated to evaluate the accumulation of [(11)C]acetate. The prostate was clearly visualised and distinguished from adjacent organs in PET images in most of the cases. The SUV of the prostate (2.6+/-0.8) was significantly higher than that of the rectum (1.7+/-0.4) or bone marrow (1.3+/-0.3) ( P<0.0001 in each case). The SUV of the normal prostate of subjects aged <50 years (3.4+/-0.7) was significantly higher than both the SUV for the normal prostate of subjects aged > or =50 years (2.3+/-0.7) and that of subjects with BPH (2.1+/-0.6) ( P<0.01 in each case). The primary prostate cancer in six cases was visualised by [(11)C]acetate PET. However, the difference in the SUV between subjects aged > or =50 with normal prostate or with BPH and the patients with prostate cancer (1.9+/-0.6) was not statistically significant. There was also no significant difference in the E/L ratio between subjects aged > or =50 with normal prostate (0.98+/-0.04) or BPH (0.96+/-0.08) and patients with prostate cancer (1.02+/-0.12). In conclusion, a normal prostate exhibits age-related physiological accumulation of [(11)C]acetate. Careful interpretation of [(11)C]acetate PET images of prostate cancer is necessary because the SUV and the E/L ratio for the normal prostate and for BPH overlap significantly with those for prostate cancer.     

Clinical role of (18)F-FDG PET for initial staging of patients with extrahepatic bile duct cancer

In extrahepatic bile duct cancer, preoperative evaluation is important because only surgical excision of all detectable tumours is associated with improvement in 5-year survival. However, morphological imaging techniques, including computed tomography (CT), are still insufficient for accurate staging. The purpose of this study was to assess the additional value, in relation to CT, of 2-[(18)F]fluoro-2-deoxy- D-glucose positron emission tomography ((18)F-FDG PET) for the evaluation of extrahepatic bile duct cancer. Thirty patients with extrahepatic bile duct cancer underwent both (18)F-FDG PET and CT for initial staging. The results of the two modalities for evaluation of primary tumours and regional lymph nodes were compared with the final diagnoses based on pathological or clinical findings. The primary tumours were interpreted as malignant on the basis of CT in 24 (80%) of the patients, while (18)F-FDG PET revealed increased (18)F-FDG uptake in 18 (60%) of them. On the other hand, (18)F-FDG PET showed focal accumulation of (18)F-FDG in the bile duct in three of the six patients with equivocal findings on CT. The sensitivity, specificity and accuracy of CT for regional lymph node metastases were 54%, 59% and 57%, while those of (18)F-FDG PET were 38%, 100% and 73%, respectively. The specificity of (18)F-FDG PET for regional lymph node metastases was significantly higher than that of CT ( P<0.01). Of 14 patients with N1 or N2 disease diagnosed by CT, only seven (50%) had a final diagnosis of regional lymph node metastasis. In these 14 patients, (18)F-FDG PET accurately evaluated the N component of the disease in 12 patients (86%). In conclusion, in the initial staging of patients with extrahepatic bile duct cancer, (18)F-FDG PET offers additional value in relation to CT in evaluating both the primary tumour and regional lymph nodes.     

Decreased endothelium-dependent coronary vasomotion in healthy young smokers

Chronic cigarette smoking alters coronary vascular endothelial response. To determine whether altered response also occurs in young individuals without manifest coronary disease we quantified coronary blood flow at rest, following adenosine vasodilator stress and during the cold pressor test in healthy young smokers. Myocardial blood flow (MBF) was quantified by oxygen-15 labelled water positron emission tomography in 30 healthy men aged from 20 to 35 years (18 smokers and 12 non-smokers, aged 27.4 +/- 4.4 vs 26.3 +/- 3.3). The smokers had been smoking cigarettes for 9.4 +/- 4.9 pack-years. MBF was measured at rest, during intravenous adenosine triphosphate (ATP: 0.16 mg kg(-1) min(-1)) infusion (hyperaemic response), and during cold pressor test (CPT) (endothelial vasodilator response). Rest MBF and hyperaemic MBF did not differ significantly between the smokers and the non-smokers (rest: 0.86 +/- 0.11 vs 0.92 +/- 0.14 and ATP: 3.20 +/- 1.12 vs 3.69 +/- 0.76 ml g(-1) min(-1); P = NS). Coronary flow reserve was similar between the two groups (smokers: 3.78 +/- 1.83; non-smokers: 4.03 +/- 0.68; P = NS). Although CPT induced a similar increase in rate-pressure product (RPP) in the smokers and the non-smokers (10,430 +/- 1,820 vs 9,236 +/- 1,356 beats min(-1) mmHg(-1)), CPT MBF corrected by RPP was significantly decreased in the smokers (0.65 +/- 0.12 ml g(-1) min(-1)) compared with the non-smokers (0.87 +/- 0.12 ml g(-1) min(-1)) ( P < 0.05). In addition, the ratio of CPT MBF to resting MBF was inversely correlated with pack-years ( r = -0.57, P = 0.014). Endothelium-dependent coronary artery vasodilator function is impaired in apparently healthy young smokers.     

Cloning of the 5' upstream region of the rat p16 gene and its role in silencing.

Hypermethylation of the 5' upstream region (5' region) of the human p16(CDKN2A) (p16) gene is known to cause silencing, which is involved in a wide range of human cancers. For the rat p16 gene, its 5' region has not been cloned, and it is uncertain whether surrogate use of exon 1 alpha is adequate for analysis of p16 silencing. In this study, we observed that methylation analysis of exon 1 alpha gave false positive results in three samples of normal rat mammary epithelia and in two of six primary mammary carcinomas. Therefore, we determined the nucleotide sequence of the 5' region of the rat p16 gene. To confirm that methylation status of the 5' region is correlated with p16 expression, the methylation status was analyzed by bisulfite sequencing and methylation-specific PCR in three samples of normal mammary glands, six samples of mammary carcinomas and four cell lines. The 5' region was demethylated in all of the three normal and six carcinoma samples that fully expressed p16. On the other hand, the 5' region was highly methylated in the 3Y1 cell line, which lacked p16 expression, but without deletion. These results showed that the methylation status of the 5' region was more closely correlated with p16 expression than that of the exon 1 alpha and analysis of the methylation status is useful in examining p16 silencing in various rat tumors.     

Early detection of hypoxia with BIS monitoring during percutaneous cardiopulmonary support

We report a patient in whom hypoxia developed during percutaneous cardiopulmonary bypass (PCPS) and was detected with the lowering of the bispectral index (BIS) values. A 7-yr-old boy was managed with PCPS for the treatment of cardiogenic shock after cardiac surgery. His circulation was dependent on PCPS and pulse pressure was nearly zero. Signals by pulse oxymetry were undetectable and periodical blood gas analysis was performed to confirm proper oxygenation. BIS was monitored, and a gradual decrease in the value was observed. Careful observation also revealed darkening of the blood in the PCPS circuit and blood gas analysis showed severe hypoxia. Oxygen concentration of the gas to a PCPS oxygenator was increased immediately and new PCPS circuit was prepared. It took almost two minutes to exchange the circuit. Near circulatory arrest might have occurred during the procedure and BIS and suppression ratio (SR) became below 10 and above 90, respectively. Both returned to the previous values 30 min after the replacement of the circuit. Severe hypoxia, otherwise overlooked, was detected with BIS monitoring and BIS reflected the circulatory status of the patient, especially of the brain. This monitoring is useful to confirm proper oxygenation during PCPS.     

The effects of family interventions for the patients with mental illness in health centers focusing on the relatives' own life

Recently, the burden on relatives of patients with mental illness has been recognized and the need for support to reduce such burden has increased. In Japan, family interventions have been conducted at Health Centers, most of them focusing on the family functioning as a caregiver. However, it is also important to focus on the relative's functioning to live their own life in family interventions. In this study, we executed a program focusing on relatives' life and health, and investigated the effects of this program on both family functioning. Family intervention programs were conducted at 10 Health Centers including both urban and rural areas in Japan. A total of 102 relatives responded to the self-administered questionnaire at the first and the last session of the family interventions. We measured functioning as a caregiver using the Support for the Disabled Score and Rejective Feeling Score, and functioning to live their own life by GHQ Distress in Daily life Score, Perceived Health Condition Score and Life Satisfaction Score. During interventions, GHQ score and Distress in Daily Life score which indicate the disfunction in living their own life decreased, and Support score increased in all sample. In the short-term illness group (n = 35), only the GHQ score decreased, while in long-term illness group (n = 44) Distress score decreased and Support Score increased. The intervention program focusing on relatives' life and health may improve both family functionings to give adequate care for patients, and to live their own daily life. Results suggested that the short-term illness group requires more intensive and personal advices, and the long-term illness group need continuous support focusing on the relative's own life. Expected roles of Health Centers are cooperation with family interventions provided at hospitals and coordination of the services in the community, as well as providing family interventions in terms of relatives' life.     

Treatment of superficial esophageal cancer by external radiation therapy alone: results of a multi-institutional experience

PURPOSE: To assess the effectiveness and toxicity of external radiation therapy for superficial esophageal cancer. METHODS AND MATERIALS: During the period from March 1979 to November 1996, 78 patients with superficial esophageal cancer received radiation therapy without intracavitary irradiation at nine radiotherapy institutions in Japan. All patients had histologically-proven squamous cell carcinoma. Endoscopic ultrasonography was performed in 34 patients to discriminate mucosal from submucosal cancer. Most of the patients had received radiation therapy using conventional fractionation at an average dose of 65.5 Gy. RESULTS: The survival rates at 1, 2, and 5 years were 88%, 73%, and 45%, respectively. The local control rates at 1, 2, and 5 years were 85%, 79%, and 66%, respectively. Although the difference was not significant, the survival rate of cancer patients with a tumor invading the submucosa was lower than that of the other patients. In 6 mucosal cancer patients, local recurrence was observed in 1 patient with extensive cancer. Regional lymph node recurrence and distant failure were not observed in mucosal cancer patients, while in 28 submucosal cancer patients, the 5-year survival rate and relapse free rate were only 49% and 43%, respectively. Univariate and multivariate analysis identified age as the only significant prognostic factor. Severe late injury, such as esophageal ulcer, perforation, and bleeding, was not observed. CONCLUSION: External radiation therapy is effective for mucosal cancer. However, further investigation is needed to establish a better standard treatment protocol for submucosal cancer.     

Prospective study of external radiotherapy with and without intraluminal brachytherapy for esophageal cancer in Japan. JASTRO Study Group

To improve the results of treatment of patients with esophageal cancer, it is important to achieve good local control. Since the esophagus is adjacent to highly radiation-sensitive organs such as the lungs, bone marrow, etc., it is difficult to irradiate tumors with high doses. Although irradiation techniques have improved as a result of advances in treatment-planning equipment and irradiation equipment, there are still some patients for whom radical radiation therapy within doses that the bone marrow and lungs can tolerate is difficult with external irradiation alone. On the other hand, intraluminal brachytherapy allows high-dose irradiation of esophageal cancer with little risk to adjacent organs. However, intraluminal brachytherapy, in which the dose sharply declines with the distance from the radiation source, is suggested to be a useful technique for tumors with relatively shallow invasion. With the aim of improving the results of esophageal cancer treatment, we designed this study to establish the optimal irradiation method in radical radiation therapy for esophageal cancer by clinically evaluating external irradiation alone and in combination with intraluminal brachytherapy.     

Early massive accumulation of In-111 pentetreotide in a metastatic liver tumor of islet cell carcinoma

A 62-year-old woman was examined with In-111 pentetreotide and Ga-67 citrate. She had undergone an operation to resect a neuroendocrine tumor of the pancreas and still had masses in the liver. One of her hepatic lesions had been biopsied and acinar cell carcinoma was suspeted. Fluid in the cyst of the tumor, however, contained a high concentration of gastrin and the tumor was strongly suspected of being a metastasis from the neuroendocrine tumor of the pancreas. The hepatic tumors quickly accumulated In-111 pentetreotide immediately after the injection, but there was no Ga-67 citrate uptake in the tumor. Five months after pentetreotide scintigraphy, her hepatic tumors were resected and histologically proven to be metastasis of islet cell carcinoma. In-111 pentetreotide provides information of the somatostatin-receptor status on the tumor and supports the diagnosis made by hormonal survey.