A Japanese Multicenter Study on PET and Other Biomarkers for Subjects with Potential Preclinical and Prodromal Alzheimer's Disease.

BACKGROUND: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the "ATN" (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer's disease (AD). OBJECTIVE: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. MEASUREMENTS: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65-84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aß1-42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. RESULTS: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET-/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. CONCLUSION: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.

Risk factors for delusion of theft in patients with Alzheimer's disease showing mild dementia in Japan.

The mechanism underlying delusion in Alzheimer's disease patients has not been fully clarified; however, the occurrence of delusion is a critical issue for dementia patients and their caregivers. In Japan, delusion of theft is the most frequent delusion in AD patients. We examined the risk factors for delusion of theft in AD patients showing mild dementia. Fifty-six AD patients were administered HDS-R, MMSE and COGNISTAT, including the 'speech sample', to assess their neuropsychological and social cognitive functions. The age, years of education, presence of cohabiting family members and premorbid personality traits were obtained from family members. About 25.0% of AD patients showed delusion of theft (D-group), and 75% did not (non-D-group). About 33.3% of female patients and 5.9% of male patients were included in the D-group (p < 0.05). About 13.6% of patients who were cohabiting with family members and 66.7% of patients who were living alone were included in the D-group (p < 0.05). About 35.1% of patients who had a neurotic personality and 5.3% of patients who did not were included in the D-group (p < 0.05). There were no significant differences in scores on HDS-R, MMSE and COGNISTAT sub-scales, except for 'speech sample', between the two groups. In the 'speech sample', 38.7% of patients who understood a relationship between two boys and 12.0% of patients who did not were included in the D-group (p < 0.05). These results indicated that delusion of theft in AD patients was related to female gender, absence of cohabiting family members, neurotic personality and retained social cognitive function.

[Lung cancer in patients with idiopathic interstitial pneumonia].

The purpose of this study was to determine the outcome of surgical treatment for lung cancer concomitant with idiopathic interstitial pneumonia (IIP). Between 1994 and 2003, 673 patients with primary lung cancer were treated. Forty-four patients (6.54%) of 673 patients were complicated with IIP. Their data were retrospectively reviewed. There were 37 male and 7 female with an average age of 67 years. They underwent 7 wedge resections of the lung, 3 segmentectomies, 32 lobectomies and 2 bi-lobectomies as surgical treatment for lung cancer. Five of these 44 patients died of acute exacerbation of IIP after the operation. The exacerbation occurred in an average postoperative day of 5 (range, 3 to 7) day. Preoperative values of serum CRP, LDH, SP-D and KL-6 failed to predict the occurrence of the exacerbation of IIP after the surgery. The preoperative value of %DLCO was lower in patients with the exacerbation than patients without the exacerbation (42.3+/-9.6% versus 66.8+/-18.8%, p=0.018). The postoperative 5-year survival rate for pathological stage I lung cancer were 84.9% and 70.2% (p=0.134) for patients without IIP and patients with IIP, respectively. Although the acute exacerbation of IIP after the surgery caused catastrophic outcomes, the long-term results in surgical treatment for stage I lung cancer simultaneously concomitant with IIP were not so poor. It is very important to avoid the postoperative exacerbation and further effort and research are required to avoid the exacerbation.

[Removal of a steel bar after Nuss procedure for pectus excavatum; report of a case].

Recently, an increasing number of patients have been treated with the Nuss procedure for pectus excavatum. One of the merits is that this surgical procedure is less invasive and leads to good cosmetic results compared with the former traditional procedures such as sternal turn over. We have repaired 60 cases of pectus excavatum using the Nuss procedure at our institute since July 1999. We have experienced the removal of a steel bar, which was the first case of Nuss procedure at our institute.

[Strategy for surgical treatment for small peripheral carcinoma of the lung especially on systemic nodal dissection].

The diagnosis of small-sized (< or = 2 cm) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT), whereas unexpected extensive mediastinal involvement has been occasionally detected in such a small-sized lung cancer. We retrospectively analyzed the clinicopathological features to determinate the predictors for lymph node involvement in patients with a small-sized adenocarcinoma. One hundred and eighty one patients who underwent pulmonary resection and systematic nodal dissection for a peripheral small-sized adeno-carcinoma were reviewed. Of these, 24 patients (13.3%) had lymph node involvement. These patients were divided into 2 groups according to the existence of lymph node involvement, and the predictors for lymph node involvement were determined using univariate analysis and multivariate regression analysis. Univariate analysis revealed GGOR (ground glass opacity area/tumor area at the level of the greatest dimension of the lesion on chest computer tomography) > or = 25% (p = 0.0137) and pleural lavage fluid involvement (p = 0.0467) as predictors for lymph node involvement. No patients had lymph node involvement if their GGOR was higher than 50%. Multivariate regression analysis revealed GGOR > or = 25% (p = 0.0274), pleural tags on the lesion on chest CT (p = 0.0138) and pleural lavage fluid involvement (p = 0.0415) as predictors. We recommend performing systemic nodal dissection even if small peripheral adeno-carcinoma's maximal diameter is 20 mm or less. Systemic nodal dissection is unnecessary if the patients' GGOR > or = 50% or they do not have pleural tags or pleural lavage fluid involvement.

[Complications of major lung resections by video-assisted thoracoscopic surgery].

Lobectomy by video-assisted thoracoscopic surgery (VATS) is gradually being performed more frequently because of advantages regarding pain and pulmonary function. Complications sometimes occur during or after VATS lobectomy. The purpose of this study was to analyze the incidence and the causes of the complications. From 1997 to 2003, 185 patients underwent VATS lobectomies. Selected diseases for this approach included primary lung cancer (n = 172), metastatic lung cancer (n = 7), benign lung tumors (n = 3) and lung sequestration (n = 3). The VATS approach was converted to open thoracotomy in 15 (8.1%) of 185 patients because of bleeding (n = 8), dense hilar adenopathy (DHA, n = 3), local extent of disease (n = 3) of intraoperative cardiac trouble (n = 1). Intraoperative complications involved injury to a blood vessel (n = 21), stapling failure (n = 15), lung injury (n = 7), nerve injury (n = 3), and others. Predictive factors for injury to pulmonary arteries was DHA (OR 37.0, p < 0.0001). Postoperative surgical death occurred in 2 patients due to pneumonia. Postoperative morbidity was 22.9%. A surgical operation without any good direct or thoracoscopic view or the use of a thoracoscopic tool without knowledge of the directions on its use should be avoided. The VATS approach should be replaced by open thoracotomy if there are DHA.

[Surgery for metastatic lung tumors at our department during the last ten years].

We report on 86 cases (112 operations) who underwent surgery for metastatic lung tumors at our department during the last 10 years. The study subjects comprised 53 men and 33 women, and the average age was 51 (+/- 19) years. Of the 112 metastatectomies performed, 53 were conducted by video-assisted thoracic surgery (VATS), and 59 were performed via thoracotomy. The procedures employed for metastatectomy were lobectomy (22 cases), segmentectomy (4 cases), and partial resection. wedge resection (86 cases). The primary origin of the metastatic tumors was colorectal carcinoma in 22 cases, osteosarcoma in 13 cases, renal carcinoma in 10 cases, and breast carcinoma in 6 cases. The 5-year survival rates in subjects undergoing first and second resection for pulmonary metastases were 46% and 44%. Metastatectomy was performed 1, 2, 3, 4, 5, and 7 times in 73, 7, 1, 2, 2, 1 cases, respectively. The average number and maximum diameter of the metastatic pulmonary lesions at first metastatectomy were 1.9 and 27.6 mm. Metastatectomy is performed, as a rule, by VATS at our department, because the more highly invasive thoracotomy procedure influences the activity of the cancer cells in a suspended phase in an unfavorable manner. Furthermore, we believe that to the maximum extent possible, re-metastatectomy should also be performed by VATS. The survival rates at our institution have been satisfactory, and we attribute this to our following strict indications for metastatectomy. Re-metastatectomy should always be considered, as the survival rates are as favorable as those following the first metastatectomy.

[Anomalous systemic arterial supply to normal basal segment of the left lower lobe; report of a case].

A 28-year-old male was referred to our hospital because of hemoptysis. A chest X-ray revealed an increase of vascular marking in the left lower field and a partial defect in the lateral line of the descending thoracic aorta. An aortogram and pulmonary arteriogram showed a large artery arising from the descending thoracic aorta and supplying the left basal segment, which had no normal pulmonary arteries. A bronchoscopy showed no abnormal findings in the bronchial tree. A clinical diagnosis of systemic arterial supply to the basal segment of the left lower lung was made, and a left lower lobectomy and closure of the anomalous systemic artery by video-assisted thoracic surgery (VATS) were successfully performed. Vascular marking of the visceral pleura of left lower basal segment was observed and the anomalous arterial pressure was 84 mmHg, as high as systemic arterial pressure, during the procedure. The histopathological examination revealed normal alveolar structure, and sclerosis and hypertrophy of pulmonary arteries of the lesion (Heath-Edwards V, which means irreversible vascular changes due to pulmonary hypertension). The patient had an uneventful postoperative course and was discharged on postoperative day 8. The VATS procedure is a more useful and less invasive method for cases of systemic arterial supply to the basal segment of the left lower lung than an open thoracotomy.

[The feasibility of a limited operation for primary lung cancer].

We reviewed 33 patients who underwent a limited operation for primary lung cancer between 1980 and 1998. These cases were divided into three groups; a poor risk group consisting of 18 patients who had a high risk such as pulmonary or cardiac dysfunction and who underwent partial resection of a lung, a reduction group consisting of 9 patients who had advanced lung cancer or uncontrolled cancer of an organ other than the lung and who underwent partial resection, and an active limited operation group consisting of 6 patients who underwent segmentectomy with lymphoadenectomy for the treatment of early lung cancer. The 1 and 3-year survival rates in the poor risk group, reduction group and active limited operation group were 73.9, 60.0, 100%, and 63.4, 0.0, 100%, respectively. The results of limited operations performed for poor risk cases were satisfactory in terms of both functional state and prognosis. Limited operations performed to reduce tumor in advanced lung cancer cases did not improve the prognosis. Although an active limited operation for a case of early lung cancer remains controversial with respect to indication, it is thought that this operation is not inferior to a standard radical operation (lobotomy with mediastinal lymphoadenectomy) in selective cases in which the maximum tumor diameter is 2 cm or less. The indication for a limited operation must be further examined from aspects of tumor size, tumor histology and the other factors of the tumor.

[The validity and problems of a new staging system for lung cancer from the point of view of surgical results].

The validity and problems of the new staging system for resected lung cancer were assessed. In the new staging system for primary lung cancer, stage I is divided into two groups (A and B) on the basis of the tumor diameter. The boundary is 30 mm in maximum diameter of the tumor. On the other hand, intrapulmonary satellite nodules in the resected lung (PM1) are considered as T4. This means that a patient with PM1 is classified as stage IIIB or IV. The five-year cumulative survival rates of 191 consecutive patients of T1 or T2N0M0 who had undergone complete lung resection were calculated. The patients were divided two groups on the basis of the boundaries of the tumor diameter, such as 15, 20, 25, 30 and 40 mm (The tumor diameter in group A is the boundary and less than boundary and the diameter in group B is more than the boundary), and the cumulative survival rates of the two groups were compared. The 5-year cumulative survival rate (Kaplan-Meier survival rate) of each group and the p-value (logrank test) were 85.0%, and 0.463 in the case of the boundary of 15 mm; 84.8%, 79.9%, and 0.374 in the case of 20 mm, 82.3%, 80.0%, and 0.553 in the case of 25 mm, 79.5, 83.5, 0.524 in the case of 30 mm and 81.0%, 82.2%, and 0.783 in the case of 40 mm. In all cases, there were no significant differences between the rates in the two groups. On the other hand, 15 cases of T4N0M0 lung cancer included 12 cases of pm1, 2 cases of p3 and 1 case of d2. The five-year cumulative survival rate for T4N0M0 patients with pm1 was 71.1%, which was similar to the rate for stage I or II patients, while the two T4N0M0 patients with p3 died of recurrences of lung cancer at 10 and 13 months after the operation, and the T4N0M0 patient with d2 died of local recurrence of lung cancer 60 months postoperatively. We concluded that the sub-classification of stage I on the basis of the boundary of tumor diameter was meaningless, if the boundary was between 15 and 40 mm and that N0M0 patients with PM1 should be classified as stage II or less, or as 1 grade up of T status.

Reinforcement of a bronchial stump in VATS lobectomy.

Bronchial stump reinforcement is sometimes required for patients who have a high risk of developing a bronchial fistula. A lobectomy by video-assisted thoracic surgery (VATS) is widely used for the treatment of both stage I primary lung cancer and metastatic central lung cancer, but there has been no report on reinforcement of a bronchial stump in a VATS lobectomy. We report an aged patient with stage I primary lung cancer concomitant to diabetes mellitus who was successfully treated by VATS lobectomy with reinforcement of the bronchial stump using a pericardial fat pedicle flap. A Harmonic scalpel was very useful and effective in harvesting the fat pedicle.

[Operative results and long-term prognosis of type A acute aortic dissection].

Between 1983 and 1997, we operated upon 91 patients with type A acute aortic dissection. The dissection was localized in 22 patients and extensive in 69 patients. All patients underwent graft replacement and 61 (67%) patients underwent simultaneous replacement of ascending aorta and total aortic arch. The hospital mortality rate were 9% for the localized dissection and 21% for the extensive dissection. The actuarial survival rates in patients with localized dissection at 5 and at 10 years was 91% and 76%, whereas those in patients with extensive dissection at 5 and at 10 years was 68% and 62%. The freedom from dissection related death or reoperation in operative survivors with localized dissection at 5 and at 10 years was 100% and 83%, whereas those in patients with extensive dissection at 5 and at 10 years was 78% and 56%. The simultaneous replacement of ascending aorta and total aortic arch in patients with extensive dissection was effective to obliteration of the distal false channel, although this extended procedure has to be carefully adopted in high risk patients with associated complications such as acute dissection organ ischemia.

The reinforcement of tracheoplasty with a self-fascia lata and Gelatin-Resorcin-Formal (GRF) glue.

We examined the efficacy of protecting the suture line in tracheoplasty by using a self-fascia lata and Gelatin-Resorcin-Formal (GRF) glue. Fifteen dogs underwent a resection of four rings of the trachea and reconstruction, and we then observed them for one month; group A (n = 5) without reinforcement, group B (n = 5) with a self-fascia-lata spread with GRF glue, and group C (n = 5) with only a self-fascia-lata. In the reinforced dogs (group B, three cases, and group C, five cases), in which the continuity of the suture line had been conserved, eight cases were resistant to pressures of from 240 mmHg to 300 mmHg, and two cases (both in group B) which had a partial discontinuity of the suture line were resistant to the same pressure of 160 mmHg. But in the five dogs without reinforcement (group A), four died from infection due to leakage of the trachea within 2 weeks; only one that had a continuity of the suture line survived and was resistant to pressure of 300 mmHg. These results show that a reinforcement of tracheoplasty using a self-fascia lata and GRF glue is useful for preventing air leakage from the suture line.

[Surgical results of two cases of simultaneous carotid endarterectomy and coronary artery bypass grafting].

Reports on simultaneous revascularization operations for concomitant stenoses of the carotid and coronary arteries are many in Europe and America but few in Japan. Herein we report two cases of successful combined carotid endarterectomy and coronary artery bypass grafting. The first case was a 56-year-old male who had effort angina and a right carotid bruit with tinnitus. He was revealed to have severe stenosis of the right internal carotid artery as well as significant lesions of the right coronary artery. The second case was a 69-year-old male who had unstable angina and a left carotid bruit with a history of transient ischemic attack. Coronary angiography revealed three vessel disease and carotid digital subtraction angiography also revealed critical stenosis of the left internal carotid artery. In both cases, simultaneous carotid endarterectomy with an internal shunt and coronary artery bypass grafting were performed with a successful outcome. The use of internal shunt on reconstruction of the carotid artery was effective for protecting the brain.

Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP.

Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP). In this disorder, the vascular amyloid in tissue sections and the approximately 7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90-147. Amyloid-laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter. They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in tau protein, and are similar to those observed in Alzheimer disease. A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).

A juvenile case of frontotemporal dementia: neurochemical and neuropathological investigations.

1. An autopsy case of frontotemporal dementia with onset at the early age of 28 years is reported. 2. The neuropathological features consisted of limited, knife-like frontotemporal atrophy with severe neuronal loss, spongiform change and gliosis, which is compatible with the frontotemporal dementia. 3. Biochemical determinations disclosed that biogenic amines and their metabolites, predominant in the dopaminergic markers, were depleted in the damaged regions. 4. Since biochemical data in frontotemporal dementia are few in previous studies, it will be determined whether these biochemical changes are characteristic for the juvenile type of frontotemporal dementia or not.

[Outcome of schizophrenia--extended observation (more than 30 years) of 129 typical schizophrenic cases [III]].

We had already made a report on outcome of schizophrenia (1986). The patients, 129 typical schizophrenia, were continuously observed over 30 years in the Kawagoe Dojinkai Hospital. Recently, we again evaluated their prognoses according to the same criteria as adopted in the first report, and divided them into the following five groups. [symbol: see text]: completely remitted group (21 persons, 16.3%), [symbol: see text]: almost remitted cases now holding jobs (23 persons, 17.8%), [symbol: see text]: Slightly remitted group showing good adjustment at home or hospital (41 persons, 31.8%), [symbol: see text]: maladjusted cases always showing an unfavorable condition (25 persons, 19.4%), x : incurable cases (19 persons, 14.7%). 1) In the last 8 years, there were 30 persons (23.3% of the whole patients) who showed prognostic changes (10 persons improved, 20 persons worsen). While the second group ([symbol: see text]) has seen fewer persons (12 persons down) than previous study, the third group ([symbol: see text]) has seen more persons (9 persons up). Each three groups, that is, the first two groups ([symbol: see text] + [symbol: see text], 44 persons, 34.1%), the third group ([symbol: see text], 41 persons, 31.8%), and the forth and fifth groups ([symbol: see text] + x, 44 persons, 34.1%) accounted for a third of the whole patients. It is after 32 years on the average (extending from 21 to 50 years) from the onset of illness that they showed prognostic changes. 2) Generally speaking, catatonic patients had favorable prognoses, hebephrenic patients unfavorable ones, and paranoid patients medium ones. But 4 improved persons in the forth and fifth groups were all hebephrenic type. 3) 17 among the 30 persons who showed prognostic changes were unstable type. They took a wave-like course. 4) 27 of all the 129 patients were dead. 25 were dead from disease mentioned below. Malignancy (8 persons), Cerebral vascular disease, Pneumonia and Diabetes (3 persons), Heart-failure (2 persons), Ileus, Myocardial infarction, Hepato-cirrhosis, Gastric ulcer, Tuberculosis and Natural death (1 person). 2 persons committed suicide. 5) Outcome of 45 patients who discontinued our medical therapy became clear as follows. [symbol: see text] + [symbol: see text]: 18 persons (40.0%), [symbol: see text]: 9 persons (20.0%), [symbol: see text] + x : 18 persons (40.0%). A smaller percentage of the patients belongs to the third group ([symbol: see text]) than that of our patients who were continuously followed by us.

[A successful surgical treatment of ascending aortic aneurysm, left common carotid artery aneurysm and left subclavian artery obstruction due to aortitis syndrome in active phase].

A 24-year-old female was admitted complaining of coldness of left upper extremity and pulsating tumor of the neck. She was diagnosed as ascending aortic aneurysm, left common carotid artery aneurysm and left subclavian artery obstruction due to aortitis syndrome on examinations. Although steroid treatment appeared to be effective in controlling inflammatory reaction, the left common carotid artery aneurysm increased in size and severe neck pain started. The risk of rupture was feared, and surgical intervention was carried out in spite of aortitis in active phase. The patient underwent surgery where aneurysmectomy and graft replacement for ascending aortic aneurysm, aneurysmectomy and graft replacement using autogenous saphenous vein for left common carotid artery aneurysm and bypass grafting for left subclavian artery obstruction were performed. The histology of resected specimens of aortic wall showed active aortitis. The postoperative course was uneventful and the patient was discharged on steroid.

Neurotransmitter changes in early- and late-onset Alzheimer-type dementia.

Neurotransmitter-related markers were examined in Alzheimer-type dementia (ATD) and studied whether or not there is biochemical difference between the early- and late-onset sub-groups. Postmortem brains were obtained from neuropathologically diagnosed ATD patients and control subjects with no clinico-neuropathological findings indicative of neuropsychiatric diseases. Neurochemical data in the early- and late-onset groups were compared to the age-matched younger and older control groups, respectively, and expressed as a percentage of the mean value in the respective controls. Choline acetyltransferase activity and concentrations of serotonin and noradrenaline were more severely depleted in the early-onset ATD group than in the late-onset ATD group. These findings indicative of heterogeneity of ATD patients were discussed from the pathogenetic and therapeutic viewpoints.

[A successful surgical treatment of impending rupture of the thoracoabdominal aneurysm in the aged].

In a case with impending rupture of the thoracoabdominal aneurysm of a 78-year-old aged who was admitted to our hospital as chief complaints of dysphagia, sense of pressure in the thoracic region and bloody sputum, resection of the aneurysm and patch graft aortoplasty were carried out with the aid of partial cardiopulmonary bypass. The maximum diameter of the aneurysm was 12 cm, and adhered partially with lung, and a very thin ejected region of the wall was noted. Enlargement of the saccular aneurysm in the false lumen of the dissecting aortic aneurysm accompanying with massive mural thrombus was noted. The patch graft aortoplasty was performed because back bleeding from four sets of intercostal arteries (Th 9-Th 12) was remarkably noted. The postoperative course was uncomplicated, and dysphagia was disappeared without paraplegia. This case is considered to be the oldest one who was undergone the the thoracoabdominal aneurysm in our country.