Masazumi Tsuneyoshi

Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population The Hisayama Study

Article abstract—We followed 828 nondemented residents of Hisayama Town, Kyushu, Japan, aged 65 years or older (88.3% of the elderly population) for 7 years starting in 1985 in order to determine the type-specific incidence of dementia and its risk factors in the general Japanese population. Only two subjects were lost to the follow-up, during which period 103 subjects developed dementia. Morphologic examination of the brains of 89 subjects (86.4%) was made by autopsy or CT. We made the initial diagnosis of dementia based on the DSM-111-R criteria, with the diagnoses of vascular dementia (VD) being based on the NINDS-AIREN criteria and Alzheimers disease (AD) on the NINCDS-ADRDA criteria. The incidence of VD and AD increased with age for both sexes. The age-adjusted total incidence (per 1,000 person-years) of dementia was 19.3 for men and 20.9 for women. The corresponding rates for VD were 12.2 for men and 9.0 for women, and for AD, 5.1 for men and 10.9 for women. Among the VD subjects whose brain morphology we examined, the most frequent type of stroke was multiple lacunar infarcts (42%), but half these subjects lacked a stroke episode in their histories. Multivariate analysis showed that age, prior stroke episodes, systolic blood pressure, and alcohol consumption were significant independent risk factors for the occurrence of VD. In contrast, age and a low score on Hasegawas dementia scale were significant risk factors for AD, and physical activity was a significant preventive factor for AD. Our findings suggest that asymptomatic stroke is an important factor in the development of VD, with age, prior stroke episodes, systolic blood pressure, and alcohol consumption being independent risk factors for its occurrence. Age and a low scare on Hasegawas dementia scale are significant risk factors for AD, with moderate physical activity having a statistically significant preventive effect.

Malignant Fibrous Histiocytoma

A clinicopathologic study of 130 cases of malignant fibrous histiocytoma (MFH) of the soft tissues is reported. This malignant neoplasm principally of middle and late adults occurred most often in the proximal portions of the extremities (48%) including the thigh and buttocks (35%). MFH may be subclassified into common (storiform and pleomorphic), myxoid, xanthogranu‐lomatous, and giant cell types, the common type being accounted for 100 cases (77%) of the series. The prognosis was more favorable in patients with storiform and myxoid tumors than in patients with pleomorphic or other type tumors, the overall relative five‐year survival rate being 48%. The depth of the tumor also affected prognosis with a significantly lower survival rate in deeply situated tumors. The rate of local recurrence of the tumor was 48%. Because of incomplete informations, metastasis was confirmed in only 26 patients and was most frequently to the lung (73%). In addition, electron microscopic, histochemical and tissue culture findings in limited cases are presented, concerning the histogenesis of the MFH.

Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma

BACKGROUND/AIMS Postoperative intrahepatic recurrence of human hepatocellular carcinoma is high. Recently, the relationship between proliferating cell activity in the cirrhotic liver and occurrence or recurrence of hepatocellular carcinoma has been reported. METHODS One hundred two resected cases of small hepatocellular carcinoma of < 3 cm in diameter without venous invasion or intrahepatic metastasis were examined to ascertain the factors affecting postoperative intrahepatic recurrence. RESULTS Cumulative intrahepatic recurrence rates at 1, 3, and 5 years after surgery were 12.0%, 57.2%, and 67.6%, respectively. The log-rank test indicated that serum albumin levels of < 3.7 g/dL, alanine aminotransferase levels of more than 54 IU/L, active inflammation in the nontumorous portion, and high proliferating cell nuclear antigen labeling index in the nontumorous portion (> 23.2%) were significant risk factors for recurrence. Tumor factors, including tumor size, histological grade, or alpha-fetoprotein level, were not significant risk factors. Coxs proportional hazard model identified that serum albumin level and alanine aminotransferase level were independently associated with intrahepatic recurrence after hepatectomy. CONCLUSIONS This study suggests that the principal cause linked to either a recurrence or a second new growth of hepatocellular carcinoma in the remnant liver after hepatectomy was the state of the underlying liver parenchyma as well as other tumor factors per se.

Papillary cystic tumors of the pancreas : assessment of their malignant potential

Background. Although the biologic characteristics of papillary cystic tumors (PCT) generally indicate a good prognosis, a malignant form has been reported.

Predictive value of endoscopic ultrasonography for regression of gastric low grade and high grade MALT lymphomas after eradication of Helicobacter pylori

BACKGROUND While a close association between gastric mucosa associated lymphoid tissue (MALT) lymphoma and Helicobacter pyloriinfection has been established, there are still cases which do not respond to H pylori eradication. AIMS To investigate the clinicopathological factors which may help predict the therapeutic efficacy of H pylori eradication in gastric MALT lymphoma. PATIENTS Forty one patients with gastric MALT lymphoma, including low and high grade lesions. METHODS After endosonographic staging was determined, H pylori was eradicated in all patients, and the subsequent gastric pathological course was then investigated. RESULTS Complete regression of MALT lymphoma was observed in 29(71%) patients, partial regression in five (12%), and no regression in seven (17%). Twenty six (93%) of 28 MALT lymphomas restricted to the mucosa but only three (23%) of 13 lymphomas which invaded the deep portion of the submucosa or beyond completely regressed. Kaplan-Meier analysis for the probability of complete regression of MALT lymphoma revealed a significant difference between tumours restricted to the mucosa and those invading the submucosa deeply or beyond (p<0.05). Neither the presence of a high grade component, perigastric lymphadenopathy, nor clinical staging prior to eradication correlated with the probability of lymphoma regression. CONCLUSIONS Assessment of deep submucosal invasion by endosonography is valuable for predicting the efficacy of H pylorieradication in gastric MALT lymphoma.

Giant cell tumor of the tendon sheath (nodular tenosynovitis): A study of 207 cases to compare the large joint group with the common digit group

Clinicopathologic, enzyme histochemical, and electron microscopic findings in 207 cases (208 lesions) of giant cell tumor of tendon sheath (GCTTS) are presented. The GCTTS could be divided into two groups according to the anatomic location, the first occurring in the digits (digit group, 182 cases) and the second, in the larger joints (large joint group, 25 cases). In the majority of cases of the digit group, the tumor occurred in one of the fingers (158 cases), whereas in the large joint group, the tumor was common in the ankle (10 cases) and knee joints (8 cases). The lesion was more common in women (67%) than in men (33%). Microscopically, the GCTTS in both groups consisted of a mixture of abundant histiocyte‐like, foam, and multinucleated giant cells of the osteoclast type. However, worthy of special mention were the large clefts or wide pseudoglandular spaces lined by synovial cells and that were more striking in the large joint group than in the conventional digit group. The component cells had functional properties of macrophages, as determined in the enzyme histochemical study. Electron microscopically, the tumors consisted essentially of histiocyte‐like, fibroblast‐like, and intermediate cells, together with myofibroblasts.

Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis

Cyclooxygenasel (COX1) and COX2 mediate the rate‐limiting step in arachidonic acid me¬tabolism. Expression of COX2 mRNA and protein is often enhanced in various human cell types by inflam¬matory cytokines such as interleukin‐1β (IL‐1β) and tumor necrosis factor α (TNFα). IL‐1β enhanced ex¬pression of various prostanoids and this expression was blocked by COX2 selective inhibitors. IL‐1β markedly induced angiogenesis in vitro and in vivo, which was significantly inhibited by COX2 selective inhibitors but not by a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor. In contrast, COX2 selective inhibitors only partially blocked VEGF‐induced angiogenesis. EP2, EP4 (prostaglandin E2 recep¬tors) agonists and thromboxane A2 (TXA2) receptor agonists induced angiogenesis in vitro and in vivo; IL‐1β‐induced angiogenesis was blocked by an EP4 antagonist and a TXA2 receptor antagonist. IL‐1β in¬duced much less angiogenesis in cornea of COX2 knockout mice than that of wild‐type mice. This is the first report that COX2 and some prostanoids play a key role in IL‐1β‐induced angiogenesis.—Kuwano, T., Nakao, S., Yamamoto, H., Tsuneyoshi, M., Yamamoto, T., Kuwano, M., Ono, M. Cyclooxygenase 2 is a keyenzyme for inflammatory cytokine‐induced angiogenesis. FASEB J. 18, 300–310 (2004)

c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue).

Extragastrointestinal stromal tumor (EGIST) is a unique tumor that occurs outside the gastrointestinal tract. EGIST shows a c-kit expression and histologic appearance similar to those of gastrointestinal stromal tumor (GIST). Most GISTs have gain-of-functional mutation of the c-kit gene, and some have mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene. However, the frequency of mutation of those genes in EGISTs remains unclear. We examined the clinicopathologic features, prognostic factors, and c-kit and PDGFRA mutation in 39 cases of EGIST. Tumors with high mitotic counts (≥5/50 high power fields) or a high Ki-67 labeling index (≥10%) were significantly correlated with worse prognoses. The c-kit mutation was found in the juxtamembrane domain (exon 11) and the extracellular domain (exon 9) in 12 of 29 cases (41.4%) and 2 of 29 cases (6.9%), respectively. The PDGFRA gene mutation was found at the juxtamembrane domain (exon 12) and the tyrosine kinase domain (exon 18) in one case each. The pattern of kit and PDGFRA mutation in EGIST was essentially similar to that in GIST. Our results suggest that the c-kit and PDGFRA mutations play an important role in the tumorigenesis of EGIST. High mitotic counts and a high Ki-67 labeling index may be useful for predicting the aggressive biologic behavior in EGIST. Furthermore, STI-571, targeting c-kit and PDGFR tyrosine kinase, seems to be a possible therapeutic strategy for EGISTs, especially advanced cases.

Leiomyosarcoma of the external soft tissues. A clinicopathologic, immunohistochemical, and electron microscopic study

This clinicopathologic study concerns 25 cases of leiomyosarcoma of the external soft tissues, including an immunohistochemical survey of 19 cases and an electron microscopic examination of six. There was a female preponderance in a ratio of 16:9. The most common site of tumors was the thigh (nine cases), followed by the knee (five cases). Three tumors were located in the dermis, 9 were confined down to the subcutis, 2 involved the deep fascia, and 11 involved the skeletal muscle. Superficially located tumors were smaller than deeply located ones. According to the predominant histologic features, the tumors were classified into well (6), moderately (14), and poorly (5) differentiated. In addition to the classical microscopic features, dedifferentiated areas resembling malignant fibrous histiocytoma were noted in three primary tumors and one recurrent tumor. In six tumors, the anatomical location and histologic features were highly suggestive of leiomyosarcoma arising in the venous wall. Many tumor cells immunoreactive for actin were seen in 13 and for desmin in 9 of the 19 cases. Four tumors contained a few tumor giant cells positive for alpha‐1‐antichymotrypsin. Ultrastructurally, the tumors were characterized by smooth muscle tumor cells showing a spectrum of differentiation of varying degrees. In two cases, histiocyte‐like tumor cells were detected. The most reliable prognostic parameter was the depth of the initial tumors; all patients with a leiomyosarcoma confined down to the subcutis are living, most of them more than 5 years after excision, whereas seven of the nine patients with a tumor involving the muscle have died within 5 years after excision.

Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends.

An optimal treatment modality for patients with primary gastrointestinal lymphoma has not yet been established. This study aimed to elucidate the clinicopathologic features of this disease and the influence of therapeutic modalities on the prognosis in Japanese patients