Aortic root remodeling: functional MRI as an accurate tool for complete follow-up.

BACKGROUND: After aortic valve-sparing procedures patients should be evaluated regularly because of the risk for further disease progression in the remaining aorta as well as recurrent aortic insufficiency. The purpose of this study was to evaluate the potential of functional MRI as a single examination for complete follow-up of these patients. METHODS: Twenty-two patients with a mean age of 54 years (range 30 - 66) were prospectively examined at 1, 12, 24, 36, and 74 months postoperatively, following a Yacoub aortic root remodeling operation, using a 1.5 T MRI. The original disease was chronic aneurysm of the ascending aorta or root in 17, chronic dissection in 3, and acute dissection in 2 patients. Transverse graft diameters, regurgitant fraction, LVEDV, and cardiac index were measured using cine MRI. Results were compared to spiral computed tomography and transthoracic color Doppler echocardiography. Mean time of follow-up was 24.9 months and ranged from 1 to 74 months. RESULTS: There were 2 re-operations, 2 years after primary surgery, due to high aortic insufficiency. CT and MRI measurements of graft diameters correlated well (p = 0.4544). Mean graft diameter (mean +/- SD) was 30 +/- 3.7, 33 +/- 3.4, 36.5 +/- 1.5, 37 +/- 2.8, and 38.3 +/- 2.8 mm at 1, 12, 24, 36, and 74 months, respectively, indicating a significant increase of graft diameter (p < 0.0001). Mean regurgitant fraction as determined by MRI was 14 +/- 7, 12 +/- 9, 13 +/- 9, 15 +/- 7, and 14 +/- 9 % at 1, 12, 24, 36, and 74 months, respectively. Flow based grading of aortic insufficiency by MR imaging correlated well with color Doppler echocardiography (p < 0.0001). CONCLUSIONS: MRI provides an excellent, noninvasive, comprehensive tool for follow-up after valve-sparing aortic root reconstruction. The determination of regurgitant fraction, ventricular dimensions and functions, and graft diameters allows standardized imaging protocols with a high reproducibility, which may lead to this technique being favored for the follow-up of patients after aortic root remodeling.

No evidence for cancer-related CD44 splice variants in primary and metastatic colorectal cancer.

The expression of alternatively spliced CD44 adhesion molecules has been implicated in the pathogenesis and metastasis of colorectal cancer. Using a new set of primers for exon-specific reverse transcription-polymerase chain reaction (RT-PCR) we delineated the exact exon composition of CD44 mRNAs in normal colorectal mucosa, including isolated colonic crypts, in colorectal carcinomas and in their hepatic metastases. In addition, the surface expression of CD44 isoforms was analysed by immunohistochemistry. We identified by RT-PCR eight variant transcripts expressed in colorectal carcinomas and their metastases, but also constitutively in normal colorectal epithelia. In the normal colorectal epithelium, the surface expression of CD44 standard and variant molecules was restricted to proliferating cells at the bottom of the crypts. Despite expression of these transcripts in colorectal cancers and their metastases, monoclonal antibodies specific for standard or variant epitopes encoded by exons v5 and v6 stained only a few neoplastic lesions. These data point to a differentiation-specific CD44 expression and splicing pattern in proliferating colorectal epithelia. However, they do not support a cancer- or metastasis-specific CD44 splicing pattern. Instead, cell surface availability of CD44 epitopes was reduced rather than increased in primary tumours and particularly in liver metastases.

Expression of CD44 splice variants in normal respiratory epithelium and bronchial carcinomas: no evidence for altered CD44 splicing in metastasis.

Expression of alternatively spliced CD44 adhesion molecules has been implicated in metastatic spread of various rodent and human tumors. To determine whether specific CD44 splice variants contribute to metastatic spread of bronchial cancers, we compared the expression of CD44 splice variants in normal bronchial epithelium and bronchial cancers, including tumors which already spread to regional lymph nodes or distant organs. Variant CD44 expression was analysed by immunohistochemistry using variant exon-specific monoclonal antibodies. The precise composition of CD44 transcripts was delineated by exon-specific RT-PCR. The concurring data obtained by both methods revealed that high levels of standard CD44 and variants v5 and v6 as well as low levels of variants v7 and v10 are expressed both in normal bronchial epithelium and squamous cell lung cancers. No CD44 expression was observed in the highly metastatic small cell lung cancers and adenocarcinomas with the exception of bronchioalveolar cancers showing weak expression of standard CD44. These data suggest that expression of alternatively spliced CD44 molecules in the bronchial tract is related to the distinct differentiation of the respiratory epithelium. No correlation between expression of specific CD44 splice variants and metastasis of bronchial cancers was observed.

Expression of CD44 splice variants in normal, dysplastic, and neoplastic cervical epithelium.

Expression of splice variants of the CD44 adhesion molecule has been implicated in metastatic spread of various human tumor cells, including malignant lymphomas and colon, mammary, and gastric carcinomas, and has been correlated to a poor prognosis for the respective patients. To determine whether variant CD44 molecules might also contribute to the metastatic spread of cervical cancer, we analyzed the CD44 expression pattern in normal cervical epithelium and in low- and high-grade cervical dysplasia and compared it with invasive and metastasizing cervical cancers, including cell lines derived thereof by immunofluorescence and exon-specific PCR amplification of reverse-transcribed CD44 transcripts. We observed that normal cervical epithelium and dysplastic lesions express high levels of standard CD44 in the basal and spinous epithelial layers. CD44 molecules encompassing variant exons v5 and v6 are strongly expressed throughout the epithelium. Low levels of variants encompassing exon v7 are expressed in basal and spinous layers, with particular strength in the suprabasal layer. Low levels of epitopes encoded by v8 and v10 are expressed in the basal and spinous layers. In cervical cancers, including lymph node metastasis, we observed strong expression of v5 and v6, but almost no expression of v7, v8, and v10. Expression of the CD44 standard form appeared to be down-regulated in some cancers when compared to normal cervical epithelium. Thus, expression of variant CD44 molecules is related to distinct differentiation of mucosal squamous epithelia in the female genital tract. No correlation of the expression of variant CD44 isoforms, including the v7-v8 fusion epitope with tumor progression or lymphatic spread, was observed.