Local Hemodynamic Conditions Associated with Focal Changes in the Intracranial Aneurysm Wall.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics has been associated with wall histology and inflammation. We investigated associations between local hemodynamics and focal wall changes visible intraoperatively. MATERIALS AND METHODS: Computational fluid dynamics models were constructed from 3D images of 65 aneurysms treated surgically. Aneurysm regions with different visual appearances were identified in intraoperative videos: 1) "atherosclerotic" (yellow), 2) "hyperplastic" (white), 3) "thin" (red), 4) rupture site, and 5) "normal" (similar to parent artery), They were marked on 3D reconstructions. Regional hemodynamics was characterized by the following: wall shear stress, oscillatory shear index, relative residence time, wall shear stress gradient and divergence, gradient oscillatory number, and dynamic pressure; these were compared using the Mann-Whitney test. RESULTS: Hyperplastic regions had lower average wall shear stress (P = .005) and pressure (P = .009) than normal regions. Flow conditions in atherosclerotic and hyperplastic regions were similar but had higher average relative residence time (P = .03) and oscillatory shear index (P = .04) than thin regions. Hyperplastic regions also had a higher average gradient oscillatory number (P = .002) than thin regions. Thin regions had lower average relative residence time (P < .001), oscillatory shear index (P = .006), and gradient oscillatory number (P < .001) than normal regions, and higher average wall shear stress (P = .006) and pressure (P = .009) than hyperplastic regions. Thin regions tended to be aligned with the flow stream, while atherosclerotic and hyperplastic regions tended to be aligned with recirculation zones. CONCLUSIONS: Local hemodynamics is associated with visible focal wall changes. Slow swirling flow with low and oscillatory wall shear stress was associated with atherosclerotic and hyperplastic changes. High flow conditions prevalent in regions near the flow impingement site characterized by higher and less oscillatory wall shear stress were associated with local "thinning" of the wall.

Distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

BACKGROUND: In patients with head and neck squamous cell carcinoma (HNSCC), a squamous cell carcinoma (SCC) in the lung represents either another primary tumor or a metastasis. This distinction greatly influences patient prognosis and could guide treatment strategies, but the nature of a solitary lung nodule is often difficult to discern by use of standard clinical and histologic parameters. Comparison of genetic alterations in the tumors could resolve this dilemma. METHODS: We compared paired tumors from 16 patients with HNSCC and a solitary lung SCC for loss (i.e., deletion) of loci on chromosomal arms 3p and 9p. Losses at these loci occur early during neoplastic transformation of the respiratory tract. DNA from microdissected tumors and normal tissues was subjected to polymerase chain reaction-based microsatellite analysis. An effort was also made to distinguish primary lung cancers from lung metastases on the basis of clinical and histopathologic features. RESULTS: In most cases, comparison of genetic alterations clarified the relationship between the lung tumor and the primary HNSCC. The paired tumors from 10 patients had concordant patterns of loss at all loci suggesting metastatic spread, whereas three paired tumors had discordant patterns of loss at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings. CONCLUSIONS/IMPLICATIONS: In patients with HNSCC and a solitary SCC in the lung, microsatellite analysis provides a rapid genetic approach for discerning clonal relationships. In such patients, we found that a solitary SCC in the lung more likely represents a metastasis than an independent lung cancer. Microsatellite analysis could potentially be applied to any patient with multiple tumors, where tumor relationships are not clear on clinical, radiographic, or even histopathologic grounds.

Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis.

BACKGROUND: Despite limiting elastic recoil and late vascular remodeling after angioplasty, coronary stents remain vulnerable to restenosis, caused primarily by neointimal hyperplasia. Paclitaxel, a microtubule-stabilizing drug, has been shown to inhibit vascular smooth muscle cell migration and proliferation contributing to neointimal hyperplasia. We tested whether paclitaxel-coated coronary stents are effective at preventing neointimal proliferation in a porcine model of restenosis. METHODS AND RESULTS: Palmaz-Schatz stents were dip-coated with paclitaxel (0, 0.2, 15, or 187 microgram/stent) by immersion in ethanolic paclitaxel and evaporation of the solvent. Stents were deployed with mild oversizing in the left anterior descending coronary artery (LAD) of 41 minipigs. The treatment effect was assessed 4 weeks after stent implantation. The angiographic late loss index (mean luminal diameter) decreased with increasing paclitaxel dose (P<0.0028 by ANOVA), declining by 84.3% (from 0.352 to 0.055, P<0.05) at the highest level tested (187 microgram/stent versus control). Accompanying this change, the neointimal area decreased (by 39.5%, high-dose versus control; P<0.05) with increasing dose (P<0.040 by ANOVA), whereas the luminal area increased (by 90.4%, high-dose versus control; P<0.05) with escalating dose (P<0.0004 by ANOVA). Inflammatory cells were seen infrequently, and there were no cases of aneurysm or thrombosis. CONCLUSIONS: Paclitaxel-coated coronary stents produced a significant dose-dependent inhibition of neointimal hyperplasia and luminal encroachment in the pig LAD 28 days after implantation; later effects require further study. These results demonstrate the potential therapeutic benefit of paclitaxel-coated coronary stents in the prevention and treatment of human coronary restenosis.

Synchronous mucosa-associated lymphoid tissue lymphoma and adenocarcinoma of the stomach.

The development of simultaneous primary gastric lymphoma and carcinoma is a rare event for which a possible etiopathogenetic role for Helicobacter pylori (HP) recently has been postulated. We report a series of eight such cases diagnosed from 1980 to 1995. In two cases, both tumors arose in a gastric stump, at 26 and 34 years, respectively, after gastric resection for a duodenal ulcer. Grossly, the lymphoma and carcinoma formed a single lesion in four cases (collision tumor); they were separated in the other four cases. Histologically, all the lymphomas fit into the category of B-cell mucosa-associated lymphoid tissue lymphoma; six of them were low-grade lymphomas and two were low-grade lymphomas with a high-grade component. The adenocarcinomas were intestinal-type in four cases, diffuse in three, and mixed in one. Regarding the depth of infiltration, four carcinomas were early gastric cancers and four were advanced. All the collision tumors contained an early gastric cancer. Our observations confirmed the association of HP with gastric lymphoma and carcinoma in 4 cases. Spiral bacteria with the features of Helicobacter heilmannii were found in one case. The occurrence of two different tumors in a gastric stump, which has not been reported previously, suggests that postgastrectomy gastritis might contribute to the development of both gastric lymphoma and carcinoma.

Centrocytic-like lymphoma associated with localized amyloidosis of the large intestine.

A case of low-grade centrocytic-like (CCL) B-cell lymphoma involving the large intestine, the regional lymph nodes and the spleen is reported. In the large intestine the lymphomatous infiltrate was restricted to sites of intense antigenic stimulation (diverticula, appendix, ileo-caecal valve) and was associated with marked plasma cell differentiation and massive amyloid deposits. The immunophenotype was CD20, CD21, CD45RA/MB1/MT2, CD68, CD45 related/Ki-B3 and HLA-DR positive, and MB2, DBA.44 reactive regarding the CCL cell lymphoma subpopulation; and IgG-lambda positive regarding its plasma cell fraction.

Gastric dysplasia: a ten-year follow-up study.

The results of a ten-year follow-up study on gastric dysplasia (GD) are reported. A total of 260 cases were diagnosed, 125 of which had an adequate follow-up, 81 Low Grade Dysplasia (LGD) and 44 High Grade Dysplasia (HGD). Patients with LGD were younger than patients with HGD, while no significant difference in the mean age was found between HGD and carcinoma. LGD regressed in 49.4% of cases, persisted in 18.5% and progressed in 32.1%. HGD regressed in 4.6%, persisted in 13.6% and progressed in 81.8%. In some cases dysplasia reappeared after a long-time interval of apparent regression. In 58 cases progression to cancer was observed: in 35 cases dysplasia was associated with carcinoma (8 LGD and 27 HGD), while in 23 cases dysplasia evolved into carcinoma (14 LGD and 9 HGD). There was a good correlation between the accuracy in following up the patients and the chance of diagnosing the carcinoma at an early stage. The importance of gastric dysplasia as a marker for carcinoma, its precancerous nature and the treatment of the patients are discussed.

Nifedipine reduces pressor responsiveness to angiotensin II in pregnant women.

OBJECTIVE: We assessed the action of nifedipine on vascular reactivity to angiotensin II (AII) in pregnant women at risk for hypertension. METHODS: We studied eleven pregnant women (28-32 weeks' gestation) who had shown a 20 mmHg increase in basal diastolic blood pressure at AII infusion rates < 10 ng/kg/min (Effective pressor dose, EPD), and were therefore considered at high risk for the subsequent development of pregnancy-induced hypertension, according to Gant. After the AII infusion was completed, we allowed the patients 4 hours of rest to avoid interactions with the first test, then administered 10 mg nifedipine, and after 30 minutes repeated the test. RESULTS: In all the 11 women the EPD after nifedipine administration had significantly reverted to normal (paired t-test: p < 0.03). CONCLUSIONS: The efficacy of nifedipine in reducing the pressor response to AII suggests the involvement of intracellular free calcium in the vascular response to pressor agents in pregnancy, and supports the use of this drug in the treatment of pregnancy-induced hypertension.

Long-term follow-up in early gastric cancer: evaluation of prognostic factors.

Four hundred and fourteen cases of early gastric cancer (EGC), diagnosed between 1977 and 1993, were studied. The percentage of EGC increased from 1977 to 1984, but thereafter remained more or less stable, despite a continuous increase in the number of endoscopic examinations. Three hundred and ninety-six patients were followed up. Twenty-nine patients died from the tumour, giving a 5-year survival rate of 82.8 per cent. The 'large' size type of EGC, the presence of submucosal penetration, and lymph-node metastasis showed a highly significant association with a lower survival rate. A small number of patients died despite the presence of 'favourable' prognostic factors. Other still unknown factors may therefore be important in determining the aggressive behaviour of certain EGCs.

Prediction of gestational hypertension by cosinor analysis of second trimester blood pressure.

OBJECTIVE: We evaluated the efficacy of cosinor analysis of blood pressure (BP) at the second trimester in predicting the subsequent development of gestational hypertension. STUDY DESIGN: We performed the cosinor analysis of BP in 313 normotensive non-proteinuric nulliparous women at the second trimester. We followed the pregnancy up to delivery and recorded the subsequent occurrence of gestational hypertension (sGH). We compared data from this group of 33 patients with those from the 280 women with uncomplicated normotensive pregnancy. We used the ANOVA to compare the means, statistical significance was assessed at p < .05. RESULTS: Diastolic MESOR of women with uncomplicated pregnancy was significantly lower than the GH patients, although both groups were definitely normotensive at the time of the recording. (Diastolic: Controls M = 62.2 +/- 1.5, A = 5.1 +/- 0.7, O = 14:07, p = .0001; sGH M = 73.5 +/- 6.2m, A = 5.9 +/- 1.1, O = 14:48, p = .003; Systolic: Controls M = 108.3 +/- 2.2, A = 5.2 +/- 0.7, O = 15:00, p = .0001; sGH M = 122.4 +/- 2.1, A = 4.1 +/- 0.8, O = 15:59, p = .01) We did not find any other significant difference among the population-mean cosinors. The most sensitive cutoff of diastolic blood pressure MESOR proved to be 68 mmHg.

Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21(WAFI/CIP1) seen in native colorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposis coli (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colorectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome.