Stroke in surgery of the arteriosclerotic descending thoracic aortic aneurysms: influence of cross-clamping technique of the aorta.

OBJECTIVE: The risk of stroke caused by dislodgment of loose atheromatous plaque or mural emboli is increased by cross-clamping of the aorta. Some patients undergo descending thoracic aortic aneurysm repair with proximal aortic cross-clamping between the left common carotid artery and the left subclavian artery. The objective of this study was to determine the influence of proximal aortic cross-clamping in arteriosclerotic aneurysm or dissecting aneurysm repair. METHODS: Between May 1984 and May 2003, 81 patients underwent elective surgery for distal arch or descending aortic aneurysm repair with proximal aortic cross-clamping between the left common carotid artery and the left subclavian artery. To evaluate the influence of the proximal aortic cross-clamping, patients were divided into two groups: patients who had undergone arteriosclerotic aneurysm repair (group I, n=25) and patients who had undergone dissecting aneurysm repair (group II, n=56). RESULTS: Eight (9.9%) of the 81 patients had a stroke. Six strokes occurred in operations for arteriosclerotic aneurysm repair group I and two strokes occurred in operations for dissecting aneurysm repair group II (24 vs 3.6%; p=0.009). In-hospital mortality rates were 12% in group I and 8.9% in group II (p=0.70). Major postoperative complications included renal failure requiring hemodialysis (in 4.2% of the patients in group I and in 8.3% of the patients in group II, p=0.99) and pulmonary complication (in 20% of the patients in group I and in 16% of the patients in group II, p=0.67). CONCLUSION: Cross-clamping between head vessels should be avoided if at all possible when operating on patients who have arteriosclerotic descending thoracic aneurysms.     

Translocation (1;22)(p36;q11.2) with concurrent del(22)(q11.2) resulted in homozygous deletion of <Emphasis Type="Italic">SNF5/INI1</Emphasis> in a newly established cell line derived from extrarenal rhabdoid tumor

Malignant rhabdoid tumor (MRT) is a highly malignant pediatric cancer, which arises in various sites such as the kidney, brain, and soft tissues. Cytogenetic studies have revealed alterations of 22q11 in MRT. Recently, deletions and mutations of the SNF5/INI1 locus in 22q11.2 have been reported in MRT, suggesting that SNF5/INI1 is a tumor suppressor gene for MRT. Here we report our molecular cytogenetic study for a newly established cell line from extrarenal MRT with t(1;22)(p36;q11.2). Consequently, the reciprocal translocation was associated with the interstitial deletion of a small segment including SNF5/INI1, and another, chromosome 22, showed terminal deletion, the breakpoint of which was located 70–80 kb centromeric to SNF5/INI1, resulting in homozygous deletion of SNF5/INI1 in this cell line.     

P16-immunostaining pattern as a predictive marker of lymph node metastasis and recurrence in early uterine cervical cancer.

OBJECTIVES: We investigated the relationship between P16-immunostaining patterns and clinicopathological factors in early uterine cervix cancers and assessed whether P16-immunostaining patterns predict the prognosis of the patients with early uterine cervix cancers. METHODS: Twenty-nine early squamous cell carcinoma (SCC) specimens of the uterus were examined using immunohistochemistry for P16 expression. The P16-immunostaining pattern was classified into two groups: the homogeneous type and the heterogeneous type. P16-immunostaining patterns were evaluated in different parts of the carcinoma in situ (CIS): the center of the tumor and the front interface of the infiltrating tumor. RESULTS: All specimens were of the homogeneous type in CIS. The P16-immunostaining pattern was significantly of the heterogeneous type in the front interface of the infiltrating tumor with lymphatic invasion, vascular invasion, lymph node metastasis, and recurrence. Regarding the P16-immunostaining patterns in the front interface of the infiltrating tumor, the patients with the heterogeneous type showed a significantly worse prognosis than the patients with the homogeneous type. CONCLUSIONS: The prognosis of patients with early uterine cervical SCC may be predicted by evaluating the P16-immunostaining pattern in the front interface of the infiltrating tumor.     

A consistent region of deletion on 1p36 in meningiomas: identification and relation to malignant progression

We analyzed the genetic aberrations on chromosome arms 1p, 10q, and 14q, which are thought to be loci that include putative tumor suppressor genes in meningiomas. We initially conducted molecular genetic testing on a total of 72 tumors including 15 atypical and 8 anaplastic meningiomas using double-target fluorescence in situ hybridization. An incidence of deletion of 1p was observed in 16.3% of histologically benign, 86.7% of atypical, and 87.5% of anaplastic meningiomas. Microsatellite analysis for loss of heterozygosity on 1p, 10q, and 14q was performed in 15 tumors (6 benign, 6 atypical, and 3 anaplastic meningiomas). We detected a limited deleted region on 1p36 in two tumors and suggest a new consistent region of deletion at 1p36.21p23 distal to D1S507 and proximal to D1S214, which spans 8.21 megabases. In addition, loss of 10q was detected in two of three secondary atypical meningiomas, and loss of 14q in two of three primary anaplastic meningiomas. We suggest that one of the putative suppressor genes is located at 1p36.21p23, and that 10q loss may contribute to the malignant progression from benign to atypical meningiomas.     

<Emphasis Type="Italic">GPC5</Emphasis> is a possible target for the 13q31-q32 amplification detected in lymphoma cell lines

Comparative genomic hybridization (CGH) analyses have detected gains of copy number on 13q, especially at 13q31-q32, in cell lines and primary cases of various types of lymphoma. Since amplification of chromosomal DNA is one of the mechanisms that can activate tumor-associated genes, and because 13q amplification had been reported in various other types of tumors as well, we attempted to define by fluorescence in situ hybridization (FISH) a common region at 13q31-q32 in which to explore genes that might be targets for the amplification events. Although the commonly amplified region we defined was relatively large (approximately 4 Mb), only one true gene, GPC5, was found there. GPC5 was over-expressed in lymphoma cell lines that had shown amplification, in comparison with those that had not. Our findings suggest that GPC5 is a likely target for amplification, and that over-expression of this gene may contribute to development and/or progression of lymphomas and other tumors.     

High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in Epithelial Ovarian Cancer

High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers. However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance was analyzed. Univariate and multivariate analyses were used to determine the impact of p62 expression on overall survival. p62 was expressed in the cytoplasm (Cyto) and/or nucleus (Nuc) in primary EOCs, and an expression subtype (Cyto^High/Nuc^Low), showing high expression in the cytoplasm but low expression in the nucleus, was significantly correlated with serous carcinoma (P<0.001), advanced stage (P=0.005), presence of residual tumor (P<0.001), and low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107), the p62 Cyto^High/Nuc^Low subtype was significantly correlated with low overall survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.     

Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat

The vasodilator peptide adrenomedullin (AM) elicits diuresis and natriuresis and inhibits aldosterone secretion. The aim of this study was to better understand the role of AM in maintaining water and electrolyte balance during chronic salt loading. Male Wistar rats were divided into a high salt (HS) group that received a diet containing 8% sodium chloride (NaCl) and a normal salt group that received a diet containing 0.4% NaCl. Plasma AM concentrations as well as expression of AM mRNA in the adrenal gland and kidney were then measured after 3, 7, 14, and 28 days. After 28 days, sodium and water excretion were significantly higher in HS rats than in control, although blood pressure and fluid volume were not significantly affected. Moreover, although plasma AM remained unchanged for up to 14 days, it was increased 2.5-fold in HS rats after 28 days on a high salt diet, and there were corresponding 3-fold and 1.5-fold increases in the levels of AM mRNA in the adrenal gland and kidney, respectively. At the same time, expression of calcitonin receptor-like receptor mRNA was significantly upregulated in both kidney and adrenal gland, as was expression of receptor activity-modify protein 1 (RAMP1) and RAMP2 mRNA in the adrenals and expression of RAMP3 in kidneys. Taken together, these results suggest that AM plays a role in the regulation of water and electrolyte balance in animals chronically ingesting high levels of salt.