Surgical pathology and etiology of 278 surgically removed mitral valves with pure regurgitation in Thailand.

INTRODUCTION: There are multiple causes of mitral regurgitation. Its etiology includes floppy valve, postinflammatory disease, infective endocarditis, and other disorders. Recently, there has been an increased tendency to remove only portions of the mitral valve, causing difficulty in the determination of etiology. Our objective was to study the pathology and etiology of mitral regurgitation from surgically removed specimens. METHODS: Native mitral valve specimens surgically excised due to mitral insufficiency were examined. Etiology was determined according to macroscopic, microscopic, clinical, and operative findings. RESULTS: Among 278 mitral valve specimens, 43% were classified as floppy valve, 31% as postinflammatory disease (presumably associated with rheumatic fever), 12% as infective endocarditis, and 14% as miscellaneous group. In floppy valves, diffuse myxoid change and chordal rupture were the main findings. In postinflammatory disease, moderate neovascularization and chronic inflammatory cell infiltration were most commonly found. Aschoff bodies were found in two cases. In infective endocarditis, gram-positive cocci were found in 70% of cases. In the miscellaneous group, three cases were related to Marfan syndrome and one case was related to papillary muscle necrosis. In comparison with postinflammatory disease, the posterior leaflet in the floppy valve had a significantly longer basal free-edge length, a more frequent chordal rupture, and an higher mean age of patients. Among completely and partially excised specimens with postinflammatory disease, there were no significant differences in microscopic findings. CONCLUSION: The three most common etiologies in mitral regurgitation were floppy valve, postinflammatory disease, and infective endocarditis. Macroscopic, microscopic, clinical, and operative findings are important in the evaluation of etiology, especially in partially excised specimens.

A functional polymorphism in the matrix metalloproteinase-1 gene promoter is associated with susceptibility and aggressiveness of head and neck cancer.

Matrix metalloproteinases (MMPs) play an important role in several steps of cancer development. A single guanine insertion polymorphism (2G) in the MMP1 promoter sequence at -1,607 creates an Ets binding site and thus results in enhancing transcriptional activity. This study aimed to evaluate the contribution of this 2G polymorphism on susceptibility and aggressiveness of HNSCC. A panel of HNSCC cell lines and peritumoral fibroblasts were examined for the MMP1 genotypes and expression levels. Genomic DNA was extracted from peripheral blood of 300 patients with newly diagnosed HNSCC and from 300 age- and gender-matched cancer-free controls. Genotyping was carried out using a PCR-RFLP assay. The levels of MMP1 mRNA expression were evaluated by the quantitative RT-PCR and a correlation with different genotype was determined. Odds ratio (OR) for cancer risk were calculated using multivariate logistic regression. In addition, a correlation between the 2G/2G genotype and clinicopathological parameters was examined. Eleven out of 18 HNSCC cell lines showed the 2G/2G genotype (61%) and only 1 cell line had the 1G/1G genotype (5.6%). Cell lines with the 2G/2G genotype expressed significantly higher mean MMP1 mRNA level than those with other genotypes. In clinical model, subjects carrying the homozygous 2G/2G genotype had a higher risk of head and neck cancer compared with subjects with other genotypes (adjusted OR: 2.28; 95% CI: 1.58-3.27), controlling for major confounders. A correlation between promoter polymorphisms and the levels of MMP1 expression in cancer tissues was found, and this 2G/2G genotype was correlated with the adverse clinicopathological parameters. Finally, the highest level of MMP1 enhancement was demonstrated in the coculture of tumor cells and peritumoral fibroblasts of 2G homozygotes. These findings suggest that the presence of 2G polymorphism at the MMP1 promoter is associated with the development and progression of HNSCC.

Pathology and etiology of 110 consecutively removed aortic valves.

OBJECTIVES: To study the pathology and determine the etiology and prevalence of aortic valve disease from surgically removed aortic valve specimens. MATERIAL AND METHOD: All the native surgically excised aortic valves (AV) received from June 1997 to March 1999 (22 months) were studied macroscopically including cuspal measurements and microscopically. By preoperative echocardiographic and macroscopic studies, they were classified into functional disorders of predominant aortic stenosis (AS), aortic stenosis with regurgitation (AS-AR) and predominant aortic regurgitation (AR). The patients' medical records were reviewed and the clinical information was extracted. The etiology was determined according to the macroscopic, microscopic and clinical findings. RESULTS: Among 110 AV (76 isolated AV and 34 with concomitant mitral valves from patients aged 15-96 years, mean age 47.54 years; male:female = 1.39:1) there were 25 AS (22.73%), 34 AS-AR (30.91%) and 51 AR (46.36%) cases. Eighty-four (76.36%) were tricuspid, 16 (14.54%) were bicuspid and 10 were undetermined. Cuspal measurements of each disease were provided and compared. All AS specimens were related to moderate to severe calcification and causes included postinflammatory disease (14 cases, 56%; age range 38-67 years, mean age 53.29 years, male:female = 0.56:1), degenerative calcific change (11 cases, 44%, age range 56-76 years, male:female = 1.2:1; mean age 69 years of 5 tricuspid AV and 60.83 years of 6 bicuspid AV). In AS-AR, 29 cases (85.29%; mean age 47.10 years; male:female = 1.23:1) were attributable to postinflammatory disease and 5 cases (mean age 70.20 years; male:female = 1.5:1) to degenerative calcific change. In pure AR, there were 21 cases (age range 15-65 years, mean age 29.76 years) of postinflammatory disease, 14 cases of infective endocarditis (IE) and postIE (age range 20-63 years, mean age 42.21 years; all 10 IE cases contained gram positive cocci), 1 case (age 55 years) of bicuspid calcific change, 8 cases of AV with dilated valve ring, 5 cases of miscellaneous causes and 2 cases of indeterminate etiology. Aschoff bodies were found in 3 AR cases. Four of 18 postinflammatory AS-AR and 4 of 14 postinflammatory disease AR cases had past history of rheumatic fever. One postinflammatory AS also had infective endocarditis from gram positive cocci without clinical sign. Severe degenerative calcific change had a higher incidence of underlying diabetes (3 of 15 cases, 20%), hypertension (8 of 14 cases, 57.14%) and dyslipoproteinemia (9 of 13 cases, 69.23%) in comparison with 3.37% (3/89) for diabetes, 9.09% (8/88) for hypertension and 30.99% (22/71) for dyslipoproteinemia in other AV diseases in combination. CONCLUSION: The three common causes of severe AV functional disorders were postinflammatory disease (58.18%), degenerative calcific change (15.45%) and IE-postIE (12.72%). Underlying diseases of severe degenerative calcific change included hypertension, dyslipoproteinemia and diabetes. Macroscopic and microscopic examinations together with clinical information, echocardiographic findings and operative details are important in evaluating the etiology of valvular diseases especially in severely calcified specimens.