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Doubly committed subarterial ventricular septal defects should be closed surgically once aortic valve deformity is present before the onset of aortic regurgitation.
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BACKGROUND: The importance of angiogenesis now is well recognized. Conventionally, tumor angiogenesis is assessed by determination of microvessel density (MVD) in the surgical specimen. This study examines tumor angiogenesis using power Doppler ultrasound and a quantitative image processing system. The authors hope to develop an in vivo and noninvasive method for quantitating tumor angiogenesis. METHODS: Thirty-five patients with FIGO Stage IB-IIA cervical carcinoma exhibiting visible cervical tumors by transvaginal ultrasound were included in this study. All patients underwent radical abdominal hysterectomy and pelvic lymph node dissection. Transvaginal power Doppler ultrasound was performed before surgery to search for blood flow signals from the tumor. The intratumoral vascularity index (VI) and resistance index (RI) were calculated. The VI was defined as the number of colored pixels divided by the number of total pixels in the defined tumor section. Maximal VI and minimal RI of a certain tumor were used for analysis. Clinical and pathologic data also were recorded. The MVD of the excised tumor was assessed immunohistochemically using a monoclonal antibody against CD34. RESULTS: Significantly higher VI values were noted in Stage II tumors compared with Stage 1 tumors (19.01+/-10.90% vs. 9.09+/-6.59%; P = 0.008), tumors invad-ing+/-50% of the cervical stroma compared with tumors invading < 50% of the cervical stroma (13.20+/-8.20% vs. 5.72+/-5.00%; P = 0.003), tumors with lymphovascular emboli compared with tumors without lymphovascular emboli (17.28+/-8.26% vs. 6.98 +/- 5.09%; P = 0.001), and tumors with pelvic lymph node metastases compared with tumors without pelvic lymph node metastases (26.16+/-7.88% vs. 8.00+/-4.95%; P = 0.021). None of the variables mentioned earlier showed a significant difference in terms of the RI values. No correlation was noted between intratumoral RI and VI in respective tumors (P = 0.53). Analysis of VI revealed linear regression with regard to tumor size (P < 0.001, correlation coefficient [r] = 0.586) and depth of stromal invasion (P = 0.002, r = 0.497). In addition, the MVD exhibited a linear relation with VI (P = 0.006, r = 0.454), tumor size (P = 0.005, r = 0.465), and depth of stromal invasion (P = 0.009, r = 0.436) using simple regression analysis. No correlation could be found between MVD and RI. CONCLUSIONS: In cervical carcinoma, intratumoral VI assessment by power Doppler ultrasound and quantitative image processing system showed better correlation with tumor stage, tumor size, and pathologic findings including depth of stromal invasion, lymphovascular emboli, and pelvic lymph node metastases than intratumoral RI. The in vivo indicator of angiogenic activity (VI) is well correlated with the conventional indicator of tumor angiogenic activity (MVD). Thus, VI could be a useful parameter for the in vivo assessment of global tumor angiogenesis.
OBJECTIVE: To investigate the relationship between serum vascular endothelial growth factor (VEGF) and clinicopathological factors and to determine whether VEGF is an independent prognostic factor of ovarian cancer patients. METHODS: Fifty-six women with International Federation of Gynecology and Obstetrics stages I to IV epithelial ovarian cancer undergoing surgery were enrolled. Clinical and pathologic items were recorded. Pretreatment VEGF serum samples of the 56 women were measured by an enzyme-linked immunosorbent assay. The results were correlated to clinical data. The histopathologic items and serum VEGF influencing clinical outcome were evaluated comparatively. RESULTS: The median VEGF serum level in ovarian cancer patients was 458.7 pg/mL. The 75% quatile was defined as the cutoff level. Elevated vascular endothelial growth factor serum levels before therapy correlated significantly with poorer disease-free survival (DFS) (log rank test, P = 0.001) and overall survival (OS) (log rank test, P < 0.001) on all of the 56 patients. Besides, significantly reduced DFS (log rank test, P = 0.001) and OR (log rank test, P = 0.006) were also observed on 40 patients with residual disease less than 2 cm. High histologic grade (RR = 2.24 for DFS; RR = 2.38 for OS) and elevated serum VEGF levels (RR = 3.34 for DFS; RR = 4.47 for OS) are the prognostic factors on the 56 ovarian carcinoma patients by multivariate analyses. The advanced surgical staging (RR = 3.28 for DFS; RR = 3.84 for OS), high histologic grade (RR = 2.55 for DFS; RR = 2.44 for OS), and elevated serum VEGF levels (RR = 5.62 for DFS; RR = 5.37 for OS) are the prognostic factors for 40 ovarian carcinoma patients with residual disease less than 2 cm by multivariate analyses. CONCLUSIONS: Pretreatment VEGF serum levels might be regarded as an additional factor in predicting the outcome of ovarian cancer patients. It also could provide prognostic information in clinically relevant subsets, such as those of residual disease less than 2 cm. Anti-angiogenic therapy, if is available, might be a new treatment modality for ovarian cancer patients with poor prognosis predicted by VEGF and other clinical parameters.
BACKGROUND: From 1986 to March 1997, 128 patients diagnosed to have doubly committed subarterial ventricular septal defects (VSD) were reviewed. Patients with aortic regurgitation (AR), and aortic valve (AV) deformity or a large left-to-right shunt across the VSD were offered operation. Forty-five patients (27 men, 18 women) agreed to surgical closure of their VSDs. METHODS: Thirty-eight patients had VSD closure alone, and 7 had an additional AV repair. Other associated defects corrected at operation were closure of atrial septal defects, closure of other ventricular septal defects, ligation of patent ductus arteriosus, and repair of ruptured sinus Valsalva aneurysm. RESULTS: There was no mortality nor major morbidity associated with operation. In the 26 patients with AR and AV deformity preoperatively, valve repair was performed in 6 patients. The condition of AR improved in 4, and remained unchanged in 22 patients. In the 10 patients with a deformity of the AV and no AR preoperatively, the condition remained unchanged in 5 patients, from whom 1 had valve operation, but progressed in 5 patients postoperatively at a mean follow-up of 6.4 years. In 9 patients with no deformity of the AV and no AR preoperatively, there was no postoperative AR and no progress of valve deformity. CONCLUSIONS: Excellent results were obtained with VSD closure and AV repair. Surgical closure of VSD, if performed before the onset of AV deformity, may prevent progressive AR. If AV repair is performed after the onset of AV deformity, progressive AR may not always be prevented.
OBJECTIVE: To evaluate the fertility outcome after laparoscopic tubal anastomosis for reversal of sterilization. DESIGN: Retrospective clinical study. SETTING: A private practice affiliated with a university medical school. PATIENT(S): Two hundred two women who desired reversal of tubal sterilization. INTERVENTION(S): Laparoscopic tubal anastomosis. MAIN OUTCOME MEASURE(S): The cumulative pregnancy rate (PR) and factors that influenced the fertility outcome. RESULT(S): The cumulative PR in the 186 patients for whom follow-up data were available was 60.3%, 79.4%, and 83.3% at 6, 12, and 18 months after operation, respectively. Five patients (3.2%) had ectopic pregnancies; one of these patients subsequently conceived normally. There were no statistically significant differences in the PR according to the sterilization method used, the site of the tubal anastomosis, or the length of the fallopian tube after surgery. The intrauterine PR was 87.1% (149/171) with bilateral anastomosis and 60% (9/15) with unilateral anastomosis. The PR decreased with increasing patient age (mean [+/- SD], 35+/-3.6 years) but was still 70.6% (12/17) in patients aged 40-45 years. CONCLUSION(S): Our findings suggest that laparoscopic tubal anastomosis is a highly successful procedure. This less invasive approach could be considered the procedure of choice in patients who desire reversal of tubal sterilization.
OBJECTIVE: To quantitate vascular endothelial growth factor of cervical carcinoma and elucidate its clinical correlation. METHODS: Intratumoral protein levels of vascular endothelial growth factor were measured in 104 cervical cancer patients and in 30 cervical tissue specimens of benign gynecologic diseases as controls. The concentrations were correlated with clinical and pathologic characteristics. RESULTS: The median concentrations of vascular endothelial growth factor in cervical cancer tissues were higher than those in benign cervical tissues (180.0 versus 0.0 pg/mg of protein, P < .001). Tumors larger than 4 cm (1030.0 versus 118.0 pg/mg of protein, P < .001) and with deep stromal invasion (364.0 versus 111.0 pg/mg of protein, P = .016) had higher levels than those smaller than 4 cm or with superficial stromal invasion. Higher levels were also found in tumors with lymphovascular emboli (568.0 versus 118.0 pg/mg of protein, P = .006), parametrial invasion (582.0 versus 117.0 pg/mg of protein, P = .04), and pelvic lymph node metastasis (759.5 versus 121.0 pg/mg of protein, P = .002) than in those without. The protein levels of vascular endothelial growth factor correlated positively with tumor sizes (r = 0.340, P < .001). Tumors with overexpressed VEGF were larger (3.35 +/- 1.17 versus 2.13 +/- 1.28 cm, P < .001) and had higher incidence of deep stromal invasion (20 of 57 versus 6 of 47, P = .009), lymphovascular emboli (15 of 33 versus 11 of 71, P = .011), parametrial invasion (15 of 32 versus 11 of 72, P = .002), and lymph node metastasis (10 of 20 versus 16 of 84, P = .004). CONCLUSION: Intratumoral protein level of vascular endothelial growth factor in cervical cancer tissue correlates well with local tumor progression and tumor metastasis. Vascular endothelial growth factor might be a marker for evaluating disease severity.
The role of angiogenesis in tumorigenesis is widely accepted. Therefore, it is mandatory to develop a clinically useful method for assessing tumor angiogenesis. This study was designed to compare the 'in vivo' and 'in vitro' methods for assessing angiogenesis and to evaluate their clinical application using cervical carcinoma as a model. Ninety women with stages IB-IIA cervical carcinoma exhibiting visible cervical tumors by transvaginal ultrasound were enrolled in this study. All patients underwent radical abdominal hysterectomy and pelvic lymph node dissection. Vascularity index (VI) was assessed by power Doppler ultrasound and a quantitative image processing system. The microvessel density (MVD) of the excised tumors was immunohistochemically assessed. Both the enzyme immunoassay and immunohistochemistry methods were performed for assessing the protein levels of vascular endothelial growth factor (VEGF) in tumor tissues. Significantly higher VI, MVD and cytosol VEGF concentrations were detected in tumors with deep stromal invasion (>or=1/2 thickness) (11.43 +/- 7.25 vs. 5.87 +/- 6.81, P < 0.001; 53.0 vs. 37.0, P = 0.006, 550.0 vs. 86.0 pg/mg, P < 0.001), lymphatic invasion (12.21 +/- 7.89 vs. 6.86 +/- 6.29, P < 0.001; 53.0 vs. 40.0, P = 0.038; 930.0 vs. 110.0 pg/mg, P = 0.002), and pelvic lymph node metastasis (17.15 +/- 8.58 vs. 7.83 +/- 6.41, P < 0.001; 54.0 vs. 39.0, P = 0.02; 964.0 vs. 131.0 pg/mg, P = 0.002). VEGF-rich tumors detected by immunohistochemistry also revealed higher VI (12.26 +/- 7.96 vs. 8.05 +/- 7.62, P = 0.012), MVD (53.0 vs. 37.5, P = 0.01) and cytosol VEGF levels (745.0 vs. 98.0 pg/mg, P = 0.002). The relationships between VI values, MVD values and cytosol VEGF concentrations were linear (VI vs. MVD, r = 0.38, P < 0.001; VI vs. VEGF, r = 0.78, P < 0.001; MVD vs. VEGF, r = 0.29, P = 0.006). As revealed by the receiver operating characteristic (ROC) curve analysis, VI is better than MVD and VEGF in predicting lymph node metastasis. In conclusion, there is histological, molecular and clinical evidence supporting VI as a useful 'in vivo' indicator of tumor angiogenesis, particularly for predicting lymph node metastases in cervical carcinomas.
We describe two cases of pelvic arteriovenous malformation diagnosed with the aid of three-dimensional color power angiography. In both cases, beta-human chorionic gonadotropin (beta-hCG) increased to significant levels (8413 and 1560 mIU/ml, respectively); however, neither an intrauterine nor an adnexal gestational sac could be found. In each case, we observed an adnexal mass with several tortuous areas exhibiting abundant turbulent flow. The diagnosis of arteriovenous malformation was made and further assessment by three-dimensional color power angiography and magnetic resonance imaging (MRI) was carried out. The complex vascular anatomy of arteriovenous malformation, including its feeding vessels and drainage, was clearly depicted by three-dimensional color power angiography and correlated well with magnetic resonance angiography. Levels of beta-hCG decreased in subsequent tests, and eventually became negative 2-3 months later without and intervention. We believe that an involutional ectopic pregnancy induced the rapid growth of the arteriovenous malformations within the mesosalpinx. Three-dimensional color power angiography can be performed quickly and easily, using existing ultrasound equipment. It improves our understanding of complicated vasculature, and thus is a useful adjunct to two-dimensional and color Doppler ultrasound in the diagnosis of arteriovenous malformation.
Cervical pregnancy is frequently associated with extensive hemorrhage which, in severe cases, may be stopped only by hysterectomy. We report a case of an anembryonic cervical pregnancy diagnosed at 10 weeks, and associated with a large arteriovenous malformation. The patient was conservatively managed with simple selective uterine artery embolization. After embolization, her vaginal bleeding ceased and the level of serum beta-human chorionic gonadotropin decreased rapidly. No additional treatment was given. The patient's postoperative course was uneventful and the cervical mass had disappeared at the follow-up 4 months later. To the best of our knowledge, this is the first report of conservative management of cervical pregnancy simply by uterine artery embolization. The role of three-dimensional power Doppler ultrasonography in the assessment of cervical pregnancy and in monitoring the therapeutic response is discussed.
G2 rotavirus was prevalent in a 1993 epidemic of acute gastroenteritis in Taiwan. In this study, the genetic relationship among G2 rotavirus strains was analysed. The VP7 genes were amplified and sequenced. Except for one strain isolated in 1981, the nucleotide sequences of the VP7 genes of most of the G2 rotaviruses were very similar (identity > 97%) and were closely related to that of a Japanese G2 reference strain, S2. The genetic relatedness of G2 rotaviruses was analysed further by RNA-RNA hybridization. The genomes of the major G2 strains of 1993 did not hybridize well with those of the G2 strains of previous seasons in RNA segments 1, 6 and 7. Partial nucleotide sequences of the VP1 gene were analysed and appeared to be similar among the major G2 strains from the same epidemic (identity > 98%), whereas the identity of the VP1 genes of the major G2 strains of the 1993 epidemic to those of previous seasons was only about 84%. Since the numbers of mutations accumulated in the VP1 and VP7 genes over a period of 10 years were comparable, the significant change in the VP1 genes of the major strains of the 1993 epidemic suggests that these G2 rotaviruses had evolved by genetic reassortment.
OBJECTIVE: To investigate the pathological significance of intra-tumoural blood flow signals detected by colour Doppler ultrasound and their association with angiogenesis in cervical carcinoma. DESIGN: A prospective cross-sectional study. SETTING: University hospital. POPULATION: One hundred and four women with Stage IB-IIA cervical carcinoma. METHODS: All women underwent radical hysterectomy and pelvic lymph node dissection. Transvaginal colour Doppler ultrasound was performed before surgery to search for arterial blood flow signals within the tumours. Tumours with a measurable intra-tumoural resistance index were defined as tumour with detectable blood flow and the others as tumour with undetectable blood flow. The microvessel density of the excised tumour was assessed immunohistochemically. The women's clinical and pathologic data were recorded. RESULTS: There were 60 tumours (58%) exhibiting detectable intra-tumoural blood flow signals. Tumours with detectable blood flow were larger, had deeper cervical stromal invasion, a higher incidence of parametrial invasion and pelvic lymph node metastases, and a higher microvessel density, when compared with those without detectable blood flow. Cervical cancers with deep cervical stromal invasion, parametrial invasion, and pelvic lymph node metastasis had higher microvessel density than those with superficial stromal invasion, no parametrial invasion, or no lymph node metastasis. Microvessel density correlated well with lymph node metastases and parametrial invasion by multiple regression analysis, while intra-tumoural blood signals only showed correlation with parametrial invasion. In the prediction of pelvic lymph node metastases and parametrial invasion, colour flow Doppler had a sensitivity of 0.80 and specificity of 0.48 in predicting lymph node metastases, and sensitivity of 0.91 and specificity of 0.57 in predicting parametrial invasion. CONCLUSIONS: The characteristics of blood flow signals in cervical carcinoma detected by colour Doppler ultrasound are associated with tumour angiogenesis and could reflect the likelihood of parametrial invasion and lymph node metastases in cervical carcinoma. The intra-tumoural blood flow signals might be used as a screening test in predicting parametrial invasion and pelvic lymph node metastases. These findings may be helpful in planning treatment for women with Stage I and II cervical carcinoma.
To establish a sensitive, specific and reproducible PCR assay for the detection of Mycobacterium tuberculosis, we evaluated three target DNAs: IS6110, 65 kDa heat shock protein gene; and mtp40 genomic fragment. We purified genomic DNA from 15 mycobacterial strains including four M. tuberculosis isolates, four M. bovis BCG isolates, and one of each for M. fortuitum, M. avium, M. intracellulare, M. szulgai, M. scrofulaceum, M. chelonei, and M. gordonae from the culture and used them as the template DNA. We studied 3 primer sets for IS6110, 2 primer sets for 65 kDa, and 3 primer sets for mtp40. Depending on the assay, these primer sets were used in the single-step PCR and/or nested PCR. The PCR assay targeting the 65 kDa protein gene could detect all of the tested mycobacterial strains, whereas targeting the IS6110 sequence resulted in detection of only M. tuberculosis and M. bovis BCG. Furthermore, targeting the mtp40 genomic fragment could be used to distinguish M. tuberculosis from M. bovis BCG. Using a nested PCR assay with primer sets specifically targeting the IS6110 or 65 kDa, we have been able to detect single copy M. tuberculosis genomic DNA. When the mtp40 genomic fragment was used as the target DNA, the sensitivity of detection was 10 copies of M. tuberculosis genomic DNA. This assay was demonstrated to have good sensitivity and specificity for detection and discrimination of mycobacterial species, and could be used in analyzing the clinical samples with low copy number infections such as the cerebrospinal fluid from the patient with tuberculous meningitis.
The Fontan operation has been used to palliate patients with a functional single ventricle. In many such patients the operative risk for a Fontan procedure is high. The bidirectional cavopulmonary anastomosis (BCPA) is a useful intermediate palliative procedure before Fontan correction. It may reduce the deleterious sequelae of chronic hypoxaemia and long-term ventricular overload, thus yielding a more suitable Fontan candidate. We reviewed our experience of 9 patients with univentricular hearts who were at the time of the BCPA not considered suitable candidates for conventional Fontan operation. Two patients had double inlet right ventricle (DIRV) with pulmonary stenosis (PS) and ventricular septal defect (VSD), 2 had univentricular heart, 4 had tricuspid atresia (TA) and hypoplastic right ventricle (RV), 1 patient had atrioventricular septal defect (AVSD) with double outlet right ventricle (DORV) with hypoplastic RV. Two of the 9 patients had bilateral superior vena cavae. All except one had undergone prior palliative operations. The mean age at BCPA was 4.7 years (range 1.5 years to 6 years) and the mean weight at surgery was 15 kg (range 7 to 22 kg). There were no operative deaths. The mean hospitalization stay was 8.5 days (range 5 to 13 days) with a mean follow up of 14 months. Median oxygen saturation improved from 78.7 +/- 6.3% to 85.9 +/- 3.9%. The BCPA is a useful palliative procedure to stage Fontan type reconstruction in selected patients with univentricular hearts.
BACKGROUND AND PURPOSE: Dynamic gadolinium-enhanced MR imaging has been used successfully to identify post-treatment recurrence or postoperative changes in rectal and cervical carcinoma. Our purpose was to evaluate the usefulness of dynamic gadolinium-enhanced MR imaging for distinguishing recurrent inverted papilloma (IP) from postoperative changes. METHODS: Fifteen patients with 20 pathologically proved lesions (recurrent IP, 12; fibrosis or granulation tissue, eight) were enrolled in the study. Three observers, blinded to pathologic results, independently evaluated conventional MR images, including T1-weighted (unenhanced and postcontrast), proton-density-weighted, and T2-weighted spin-echo images. Results then were determined by consensus. Dynamic images were obtained using fast spin-echo sequences at 5, 30, 60, 90, 120, 150, 180, and 300 seconds after the injection of gadolinium-diethylene-triamine penta-acetic acid. Time-signal intensity curves of suspected lesions were analyzed by a pharmacokinetic model. The calculated amplitude and tissue distribution time were used to characterize tissue, and their values were displayed as a color-coded overlay. RESULTS: T2-weighted images yielded a sensitivity of 67%, a specificity of 75%, and an accuracy of 70% in the diagnosis of recurrent IP. Contrast-enhanced T1-weighted images yielded a sensitivity of 75%, a specificity of 50%, and an accuracy of 65%. Pharmacokinetic analysis showed that recurrent IP had faster (distribution time, 41 versus 88 seconds) and higher (amplitude, 2.4 versus 1.2 arbitrary units) enhancement than did fibrosis or granulation tissue. A cut-off of 65 seconds for distribution time and 1.6 units for amplitude yielded a sensitivity of 100% and a specificity of 100% for diagnosing recurrent IP. CONCLUSION: Dynamic MR imaging can differentiate accurately recurrent IP from postoperative changes and seems to be a valuable diagnostic tool.
Enzymatic dissolution of haemothorax is highly effective in the evacuation of proteinaceous material from the pleural space. Its use in postcardiotomy haemothorax has not been described. We report the case of a 4-year-old girl with Fallot's Tetralogy diagnosed at birth. She underwent a total correction of Fallot's Tetralogy at 4 years of age. Chest X-ray taken post-operatively showed a large pleural collection in her right haemithorax. Repeated intraplueral infusion of purified streptokinase into the right upper pleural chest tube greatly reduced the extent of the right haemothorax. Enzymatic dissolution of haemothorax by purified streptokinase has proven to be a rapid and successful method of therapy. It has provided an alternative which is less invasive and has a low morbidity.
OBJECTIVE: To determine the effects of different dosages of conjugated equine oestrogen on the bone mineral density of postmenopausal Hong Kong Chinese women. DESIGN: A 1-year three-arm randomised controlled trial. SETTING: Out-patient setting at a governmental hospital in Hong Kong. PARTICIPANTS: One hundred and five women aged 45 years or older, in whom menopause had occurred not more than 2 years previously. INTERVENTION: Women were assigned randomly to treatment with conjugated equine oestrogen 0.625 mg/d or 0.3 mg/d, or no oestrogen. MAIN OUTCOME MEASURE: Bone mineral density. RESULTS: Women who were assigned to the control group showed a significant reduction in bone mineral density in both the femoral neck and the lumbar spine (3.6%; P=0.001 and 4.0%; P<0.001, respectively). Those who received oestrogen 0.3 mg/d showed a significant reduction (3.9%; P=0.010) and a non-significant reduction (2.2%; P=0.141) in their lumbar spine and femoral neck bone mineral densities, respectively. In contrast, there was little change in the spinal and femoral neck bone mineral densities in women who received estrogen 0.625 mg/d. CONCLUSION: The minimum effective dosage of conjugated equine oestrogen to prevent osteoporosis in postmenopausal Hong Kong Chinese women is 0.625 mg/d. The bone mineral density, however, was maintained but not increased.
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