Biomedical subjects

I Novikov

Publications and source records attributed to I Novikov.

At least 19 recordsLinked to original sources

PubMed2001

Topoisomerase II immunostaining as a prognostic marker for survival in ovarian cancer.

OBJECTIVE: This study aimed to evaluate topoisomerase II compared to Ki-67 expression as a marker for tumor behavior and for prognosis of patients with ovarian cancer. METHODS: In order to screen for potential prognostic markers, two groups of patients with advanced stage (FIGO stages III and IV) epithelial ovarian carcinoma were selected based on differences in survival (mean survival, 11 years versus 2 years). Pathology slides were reviewed, and immunohistochemistry using antibodies to topoisomerase II and Ki-67 was performed on the original cell blocks. No patients were lost to follow-up. RESULTS: Detectable expression of topoisomerase II was present in 70.0 +/- 30.3% of cells in patients with rapidly progressing disease, compared to only 12.3 +/- 12.4% of cells in long-term survivors (P = 0.0001). Ki-67 expression was also more frequent in short-term survivors compared to long-term survivors, but the difference was less prominent than with topoisomerase II (P = 0.01). Specificity and sensitivity as prognostic factors reached 88.2 and 93.8% for topoisomerase II, compared to 55.6 and 88.2% for Ki-67. CONCLUSIONS: Topoisomerase II expression as detected by immunohistochemistry in tumor samples emerged as a promising clinically relevant biomarker for survival in advanced epithelial ovarian cancer.

Biomarkers, Tumor↗

PubMed2001

Outcome of twin pregnancies with extreme weight discordancy.

The objective of this paper is to examine the outcome of pregnancies with extreme weight-discordant twins. Percentage of birth weight discordancy was defined as the birth weight difference between the twins divided by the larger twin's weight and multiplied by 100. Discordancy was calculated for all twin births in which both fetuses were live born. In 33 pairs, the discordancy was defined as extreme (>35%) and they constituted the study group. Thirty-three pairs of twin defined with mild weight discordancy (15-25%), and 33 pairs defined as concordant to birth weight (<15% difference) were matched to the study group patients based on gestational age at delivery (+/- 7 days) and on the mode of delivery, and constituted the control groups. The records of all the patients were reviewed for pregnancy complications and for major and minor neonatal outcome variables. Significantly more parturients in the study groups were primiparous undergoing in vitro fertilization treatments to conceive. Significantly more women in the study group had severe preeclampsia compared with women with mild discordancy or concordant twins (12.1 vs. 3.0% and 0%, respectively, p <0.025). No significant differences were encountered between the groups in neonatal mortality or morbidity factors except an increased rate of hyperbilirubinemia in the study group, p = 0.006. Using logistic regression analysis, discordancy was not defined as an efficient predictor for adverse neonatal outcome. Twin pregnancies with extreme discordancy have a favorable neonatal outcome in correlation with gestational age and not with the percentage of discordancy.

Apgar Score↗

PubMed2001

Laryngotracheal anastomosis: primary and revised procedures.

OBJECTIVES: Acquired upper airway stenosis is usually associated with a complex of pathological conditions at the high tracheal and the subglottic levels. Reported reconstructive techniques include widening by incorporation of grafts, segmental resection, and anastomosis or combined procedures. The management of recurrent stenosis after reconstructive surgery is a major challenge and has rarely been discussed in the literature. The purposes of the present study are to compare the clinical course of primary versus revised reconstructive procedures and to analyze the effect of age, diabetes, chronic lung disease, grading of stenosis, extent of resection, and revised procedures on the operative rate of success. STUDY DESIGN: A cohort study in a tertiary referral medical center. METHODS: The clinical course of 23 consecutive patients undergoing laryngotracheal anastomosis was studied comparing a group of 13 primary with 10 revision procedures. Seventeen patients underwent cricotracheal and six patients thyrotracheal anastomoses. All patients but one were tracheotomized before the definitive reconstructive procedure. Suprahyoid release was routinely performed except for two cases, and only one patient required sternotomy. The Wilcoxon test was used to examine the relationship between preoperative clinical parameters and the postoperative success (i.e., airway patency). RESULTS: Twenty-two of 23 patients (95.6%) had successful decannulation. Four patients required a revision procedure because of repeat stenosis at the site of the anastomosis (2) or distal tracheal malacia (2). Residual airway stenosis of less than 50% was noted in six patients, although only three complained of dyspnea during daily-activity exertion. There was no associated mortality. Complications included subcutaneous emphysema (4), granulation tissue formation (3), pneumonia (2), cardiac arrhythmia (2), and one each of pneumomediastinum, neck hematoma, and urosepsis. Protracted aspirations were noted in one patient who had revision surgery. Age was the only parameter that correlated with postoperative airway patency (P <.07), whereas the presence of chronic obstructive lung disease and diabetes, grade of stenosis, type of surgery, and revision surgery were found to be insignificant. CONCLUSIONS: The clinical course of laryngotracheal anastomosis in primary and revised procedures was similar in our group of patients. The operation can be performed safely, with an expected high rate of success and acceptable morbidity.

Anastomosis, Surgical↗

PubMed2000

Selected risk factors for transitional cell bladder cancer.

Cancer of the bladder has long been associated with environmental risk factors, such as occupational hazards and smoking. The aim of the current study was to evaluate the contribution of known risk factors on a community basis in the 1990s, in view of the recent worldwide efforts to control environmental hazards. The study population included 140 male patients and 280 matched controls. Information on demographic data, occupational exposure, smoking habits and disease history was obtained by personal interviews. Our study confirmed the role of industrial occupation (OR=2.21; 95% Cl=1. 21-4.02) and exposure to 3 or more metals (OR=3.65; 95% Cl=1.21-11. 08) as risk factors. Prostate enlargement was also found significant, but probably not causal (OR=2.23; 95% Cl=1.29-3.87). Surprisingly, smoking showed only an inconsistent association with higher rates among those who started to smoke before 18 years of age (OR=2.64; 95% Cl=1.4-4.99) and those who smoked more than 30 cigarettes per day (OR=1.82; 95% Cl=0.95-3.49). The above data suggest that current efforts to reduce the load of bladder cancer in the population, via environmental measures, have not as yet yielded significant effects.

Adult↗

PubMed2000

The epidemic of ankle fractures in the elderly--is surgical treatment warranted?

Ankle fractures in the elderly are extremely common (up to 184 fractures per 100,000 persons per year, and of these approximately 20%-30% occur in the elderly). The medical literature contains no research that has investigated ankle fractures in the elderly. A prospective, randomised study was conducted of 84 patients with displaced ankle fractures, who were over the age of 65 years and were assigned to operative or conservative treatment after closed reduction. The results of treatment assessed according to the American Orthopedic Foot and Ankle Society (AOFAS) Score showed a mean of 91.37 +/- 8.96 in the non-operated group compared with 75.2 +/- 14.38 (P = 0.001) in the operated group. The costs of treatment were accordingly higher. These results call for consideration of a non-operative approach to the treatment of well-reduced ankle fractures in the elderly. Increased efforts should be invested in the prevention of these common fractures.

Age Factors↗

PubMed2000

Standardization criteria for the detection of BCR/ABL fusion in interphase nuclei of chronic myelogenous leukemia patients by fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH), as a new clinical test, is not presently standardized. For practical reasons, each laboratory must build its own criteria. In this work, we present our standardization criteria for clinical practice, which include not only the methods for cell fixation, specimen preparation, and hybridization conditions, but mainly the definition of false-positive range and the scoring criteria of microscopic analysis. These include signal assessment, difference between individual microscopists, evaluation of specimen homogeneity, and the minimum number of scored nuclei required for a clinically reliable result. For this purpose, we analyzed by FISH 24 healthy volunteer donors, 31 patients affected by non-chronic myelogenous leukemia (CML) hematological malignancies, 47 CML patients at diagnosis, and 82 CML patients during treatment for the BCR/ABL fusion. In this article, we present several quality control and assurance methods that can be useful in providing standardization of the FISH technique.

Cell Nucleus↗

PubMed2000

Expression of topoisomerase II and Ki-67 in cervical carcinoma--clinicopathological study using immunohistochemistry.

AIM: To study the correlation between the expression of topoisomerase II and Ki-67 antigen and disease outcome in cervical squamous cell carcinomas. EXPERIMENTAL DESIGN: Forty-nine cervical carcinomas, 10 cases of high-grade cervical intraepithelial neoplasia (CIN II-III) and 5 control cervices were stained by monoclonal antibodies for topoisomerase II and Ki-67 (MIB-1 clone). Nuclear counts were correlated with patient age, tumor stage, histological grade and survival. RESULTS: Thirteen patients died of disease, 35 remained free of disease, and one patient was lost to follow up. Ki-67 counts were higher in CIN lesions, when compared to both invasive carcinomas and control cervices. Topoisomerase II counts were comparable for CIN and invasive tumors. No immunoreactivity for topoisomerase was detected in control cases. Neither stage nor grade was associated with nuclear counts using either marker. In multivariate survival analysis, stage (p=0.001), grade (p=0.03) and older patient age (p=0.02) predicted poor survival. Ki-67 counts predicted survival with borderline significance (p=0.07), while topoisomerase II counts were not related to survival. CONCLUSION: Ki-67 and topoisomerase II counts do not appear to have a significant role in the prediction of survival in cervical squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed2000

CA 125 measurement and ultrasonography in borderline tumors of the ovary.

OBJECTIVES: Our goal was to perform an analysis of ultrasonographic characteristics and CA 125 levels in ovarian tumors of borderline malignancy. STUDY DESIGN: We performed a retrospective analysis of CA 125 levels and ultrasonographic parameters in 91 patients with borderline tumors. RESULTS: Serous tumors of borderline malignancy were associated with elevated CA 125 levels in 75% of patients before surgery (mean, 156 IU/mL) compared with 30% of mucinous tumors (mean, 28 IU/mL; P =.004). CA 125 was elevated in 35% of stage IA serous tumors (mean, 67 IU/mL) compared with 89% of tumors with spread beyond the ovary (mean, 259 IU/mL; P =.001). Mucinous tumors tended to be bigger (13.1 +/- 7 cm) on ultrasonography than serous tumors (9.3 +/- 6.2 cm, P =.016). Mucinous tumors were multilocular in half the patients and contained papillations in 40% of the patients. Serous tumors were multilocular in 30% of the patients but presented with solid or papillary patterns in 78% of the patients (P =.001). A resistance index of <0.4 was found in 36% of mucinous tumors and half the cases of serous tumors. In 13% of patients, ultrasonographic characteristics were compatible with a simple cyst only, including 1 patient with microinvasion and 1 patient with stage IIIB disease. Sensitivity of gray-scale ultrasonography was 87%, that of CA 125 measurement was 62%, and that of flow was 55%. At least 1 diagnostic test result was abnormal in 93% of patients, 2 were abnormal in 69% of patients, and all 3 were abnormal in 21% of patients. CONCLUSIONS: A high proportion of borderline tumors of the ovary, particularly of the serous type, were associated with elevated CA 125 levels and abnormal ultrasonographic characteristics, although some tumors presented as simple cysts.

Adolescent↗

PubMed2000

Modulation of ventricular fibrillation in the isolated heart: the role of slow calcium channel activity under continuous perfusion.

The individual activities of sodium versus calcium channels in the initiation and maintenance of ventricular fibrillation (VF) have not been fully elucidated. Therefore we studied in isolated heart under nonischemic conditions (a) VF characteristics in untreated hearts, (b) initiation and maintenance of VF during attenuation and blockade of slow calcium channel activity by verapamil, (c) the effect of these interventions on the characteristics of the induced arrhythmia, and (d) the impact of heart weight on the observed results. Measurements were carried out in both ventricles of isolated feline hearts during ventricular pacing and 8 min of electrically induced tachyarrhythmias. Measurements during ventricular pacing included epicardial conduction time (CON), refractoriness (VRP), and all tissue resistivity (ATR; an indirect measure of changes in intercellular electrical coupling). Measurements during arrhythmia included ATR, peak frequency [PKF; a measure of the prevailing frequency based on Fast Fourier Transform (FFT) analysis], and normalized entropy (ENTROP; a measure of the degree of arrhythmia organization). Measurements during sinus rhythm and arrhythmia were repeated after blocking of calcium channel activity by verapamil at a high concentration (1.8x10(-4) M; n = 8) and at two low concentrations (1.5 and 3.0x10(-7) M; n = 8). In untreated hearts, mainly VF episodes were induced, exhibiting a low degree of organization with no significant change in this parameter throughout the arrhythmia (8 min). In the left ventricle (LV; and to a much smaller extent in the right ventricle; RV), a gradual increase in PKF was observed throughout the arrhythmia, with no significant change in ATR. Verapamil at a high concentration increased CON, but did not affect VRP. These findings were similar in both ventricles. In lower verapamil concentrations, CON was not affected, and VRP was slightly shortened. After treatment with a high verapamil concentration, VF could not be induced in small hearts but was always inducible in large hearts. Transient arrhythmia episodes appeared in 9% of untreated hearts, in 25% with "high" verapamil, and in 25-37% with "low" verapamil. With all verapamil concentrations, the induced arrhythmia was modulated from a predominantly VF to PVT or MVT type, manifested by a decrease in ENTROP. This effect was less pronounced with increasing heart weight. No significant change in PKF and in ATR was obtained with verapamil throughout the arrhythmia. It is suggested that verapamil modulation of arrhythmia organization is associated mainly with a direct blockade of calcium channel activity (perhaps by causing reduction in the safety factor for conduction), rather than with indirect modulation of electrophysiological parameters.

Animals↗

PubMed2000

Role of sodium channels in ventricular fibrillation: a study in nonischemic isolated hearts.

Because the role of sodium channels in the initiation and maintenance of VF is not fully elucidated, we studied the significance of sodium channel activity in VF using sodium channel blockers. In nonischemic isolated feline hearts, the following electrophysiologic parameters were measured before and after application of tetrodotoxin (5 x 10(-7) M, n = 6) or lidocaine (1 x 10(-5) M, n = 8): (a) during pacing, epicardial conduction time; refractoriness; the fastest rate for 1:1 pacing/response capture, and all tissue resistivity, indirectly reflecting intercellular electrical resistance; (b) during 8 min of electrically induced tachyarrhythmias, all tissue resistivity; peak frequency (to measure average frequency based on fast-Fourier transformation analysis); and normalized entropy (to measure the degree of arrhythmia organization). In nonischemic isolated rabbit hearts (n = 4), three-dimensional mapping was performed before and after application of lidocaine (1 x 10(-5) M). In feline hearts, lidocaine and tetrodotoxin application resulted in: (a) more spontaneous arrhythmia termination (63-67%) than in nontreated hearts (7%); (b) transformation from mainly VF into ventricular tachycardia with increased organization; and (c) prolongation of conduction time (155-248%) (p < 0.01 for all parameters). The ventricular refractory period was slightly prolonged by tetrodotoxin in the right ventricle and exhibited rate-dependent shortening in control and with lidocaine. Tetrodotoxin and lidocaine reduced the pacing rate for 1:1 pacing/response capture, and all tissue resistivity was not significantly affected. Peak frequency was decreased by tetrodotoxin and lidocaine mainly in the left ventricle (p < 0.01). In nontreated left ventricles, peak frequency was increased over time but was attenuated by lidocaine. In isolated rabbit hearts, several simultaneous wave fronts were detected during VF in nontreated hearts and were reduced to only one or two major wavefronts after application of lidocaine. Suppression of sodium channel activity that primarily slowed conduction time and had little or no effect on ventricular refractory period and all tissue resistivity resulted in less stable and more organized arrhythmias and reduced tachyarrhythmia rate compared with nontreated hearts. These results suggest an active role for sodium channels in the maintenance of ventricular fibrillation.

Anesthetics, Local↗

PubMed1999

Patterns of late corneal scarring after photorefractive keratectomy in high and severe myopia.

OBJECTIVE: To study the correlation between scarring 1 year after photorefractive keratectomy (PRK), final refraction, and degree of myopia. DESIGN: A retrospective, noncomparative case series. PARTICIPANTS: One hundred twenty eyes of 78 patients underwent PRK for high and severe myopia. Thirty-nine eyes had a pre-PRK spherical equivalent (SE) between -9.5 and -18.25 diopters (D) (severe myopia). Eighty-one eyes had a pre-PRK SE between -6.25 and -9.25 D (high myopia). Follow-up time ranged between 12 and 37 months with a mean of 18.2 months. INTERVENTION: Multizone PRK with the VISX 20/20 excimer laser. MAIN OUTCOME MEASURES: Corneal scarring, final best-corrected visual acuity (BCVA), and refraction. RESULTS: There were 71.7% of eyes with severe myopia and 60.5% of eyes with high myopia found to have any pattern of stromal scarring, which was classified as focal, semiannular, annular, and discoid. Discoid scars were rare (6.6%) and found in 12.8% of severe myopic eyes compared to 3.7% of high myopic eyes. Only 50% of the eyes with a discoid scar achieved final BCVA between 6/6 and 6/9 compared to 81.6% of the eyes with a clear cornea. The severe myopic eyes with a discoid scar had the highest level of final undercorrection (-5.0 D) compared to a maximum of -1.5 D in the high myopia group. The severe myopic eyes with a discoid scar had a higher number of retreatments (4 of 5) compared to the high myopia group (1 of 3). Other types of scars were less clinically significant. CONCLUSIONS: Photorefractive keratectomy was efficient in the correction of high myopia but less so in severe myopia, in which discoid scarring was more frequent and more clinically significant, being associated with significant regression. Other types of scarring were less clinically significant.

Adolescent↗

PubMed1999

Vision screening of preverbal children with Teller acuity cards.

OBJECTIVE: To evaluate the modified Teller visual acuity test as a mass screening tool for testing visual acuity in infants and preverbal children. DESIGN: Prospective case series. PARTICIPANTS: A total of 1126 healthy children undergoing mandatory examination at the Mother and Child Health Center. INTERVENTION: Visual acuity was tested by the modified Teller visual acuity test. MAIN OUTCOME MEASURES: Visual acuity was measured in all children. Clinical evaluation was performed in children who failed the Teller acuity test and in a control group. RESULTS: Visual acuity was below the normal range in 5% of the children. In the study group referred for complete eye examination, there were 9% false-negative and 44% false-positive results. In the age range of 12 to 17 months, false-negative and false-positive results were obtained in 5.6% and 50% of the children, respectively. CONCLUSIONS: The Teller acuity card procedure can be used for vision screening in preverbal children. Testing was associated with a high rate of false-positive results.

Child, Preschool↗

PubMed1999

Acute myocardial infarction with isolated ST-segment elevation in posterior chest leads V7-9: "hidden" ST-segment elevations revealing acute posterior infarction.

OBJECTIVES: This study was done to determine whether electrocardiographic (ECG) isolated ST-segment elevation (ST) in posterior chest leads can establish the diagnosis of acute posterior infarction in patients with ischemic chest pain and to describe the clinical and echocardiographic characteristics of these patients. BACKGROUND: The absence of ST on the standard 12-lead ECG in many patients with acute posterior infarction hampers the early diagnosis of these infarcts and thus may result in inadequate triage and treatment. Although 4% of all acute myocardial infarction (AMI) patients reveal the presence of isolated ST in posterior chest leads, the significance of this finding has not yet been determined. METHODS: We studied 33 consecutive patients with ischemic chest pain suggestive of AMI without ST in the standard ECG who had isolated ST in posterior chest leads V7 through V9. All patients had echocardiographic imaging within 48 h of admission, and 20 patients underwent coronary angiography. RESULTS: Acute myocardial infarction was confirmed enzymatically in all patients and on discharge ECG pathologic Q-waves appeared in leads V7 through V9 in 75% of the patients. On echocardiography, posterior wall-motion abnormality was visible in 97% of the patients, and 69% had evidence of mitral regurgitation (MR), which was moderate or severe in one-third of the patients. Four patients (12%), all with significant MR, had heart failure, and one died from free-wall rupture. The circumflex coronary artery was the infarct related artery in all catheterized patients. CONCLUSIONS: Isolated ST in leads V7 through V9 identify patients with acute posterior wall myocardial infarction. Early identification of those patients is important for adequate triage and treatment of patients with ischemic chest pain without ST on standard 12-lead ECG.

Adult↗

PubMed1999

The significance of persistent ST elevation versus early resolution of ST segment elevation after primary PTCA.

OBJECTIVES: To determine the prevalence and clinical significance of early ST segment elevation resolution after primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI). BACKGROUND: Despite angiographically successful restoration of coronary flow early during AMI, adequate myocardial reperfusion might not occur in a substantial portion of the jeopardized myocardium due to microvascular damage. This phenomenon comprises the potentially beneficial effect of early recanalization of the infarct related artery (IRA). METHODS: Included in the study were 117 consecutive patients who underwent angiographically successful [Thrombolysis in Myocardial Infarction (TIMI III)] primary PTCA. The patients were classified based on the presence or absence of reduction > or =50% in ST segment elevation in an ECG performed immediately upon return to the intensive cardiac care unit after the PTCA in comparison with ECG before the intervention. RESULTS: Eighty-nine patients (76%) had early ST segment elevation resolution (Group A) and 28 patients (24%) did not (Group B). Group A and B had similar clinical and hemodynamic features before referring to primary PTCA, as well as similar angiographic results. Despite this, ST segment elevation resolution was associated with better predischarge left ventricular ejection fraction (LVEF) (44.7 +/- 8.0 vs. 38.2 +/- 8.5, p < 0.01). Group B patients, as compared with those of Group A, had a higher incidence of in-hospital mortality (11% vs. 2%, p = 0.088), congestive heart failure (CHF) [28% vs. 19%, odds ratio (OR) = 4, 95% confidence interval (CI) 1 to 15, p = 0.04], higher long-term mortality (OR = 7.3, 95% CI 1.9 to 28, p = 0.004 with Cox proportional hazard regression analysis) and long-term CHF rate (OR = 6.5, 95% CI 1.3 to 33, p = 0.016 with logistic regression). CONCLUSIONS: Absence of early ST segment elevation resolution after angiographically successful primary PTCA identifies patients who are less likely to benefit from the early restoration of flow in the IRA, probably because of microvascular damage and subsequently less myocardial salvage.

Angioplasty, Balloon, Coronary↗

PubMed1999

Epley's manoeuvre for benign paroxysmal positional vertigo: a prospective study.

The treatment of benign paroxysmal positional vertigo (BPPV) by the Epley, canalith repositioning, manoeuvre was popularized following clinical reports which demonstrated a significant success rate. Benign paroxysmal positional vertigo is considered a self-limiting disease, yet only few authors have analysed the effect of this manoeuvre in randomized, controlled terms. A prospective 3-year, controlled study of patients with BPPV of long duration (mean = 6 months) verified its benefit: the recovery course differed significantly between a group of 31 patients treated with the manoeuvre and a control group of 10 untreated patients. Symptoms subsided within 72 h in 35% and within a week in 74% of patients after one session of treatment. Only two treated patients (6.5%) did not recover versus a 50% failure rate among untreated patients (P = 0.0005). The rate of recovery was not affected by the duration of symptoms before initiation of treatment, or by the patient's age and gender.

Female↗

PubMed1999

The prognostic value of anti-paternal antibodies and leukocyte immunizations on the proportion of live births in couples with consecutive recurrent miscarriages.

Anti-paternal antibodies directed towards paternal leukocytes have been used to predict the prognosis for the subsequent pregnancy in women with consecutive recurrent miscarriages (CRM) and also to determine if the patient has become immune after paternal leukocyte immunization. The predictive value is controversial, as these antibodies are not essential for pregnancy to develop, and only occur in a minority of parous women. This study tried to determine the predictive value of these antibodies when assessed separately for women with five or more abortions and compared to women with three or four abortions. The patients were assessed separately so that the higher live birth rate in the latter group would not obscure meaningful results in the former group with a poor prognosis. Antibody production, whether spontaneous, or induced by immunization, raised the live birth rate in primary and tertiary aborters with three, four, five or more abortions. Anti-paternal antibodies increased the proportion of live births from 18.5 to 53. 7% (P </= 0.01) and from 44.4 to 67.5% (P </= 0.001) in primary aborters with >/= 5 CRM and 3-4 CRM respectively. Both immunization with paternal leukocytes per se and the ability to express anti-paternal antibodies were associated with an increased proportion of live births in the next pregnancy. Multivariate analysis showed that that the odds ratio for a live birth was approximately four times greater in women who were immunized and produced anti-paternal antibodies than in control patients. The lack of anti-paternal antibodies at initial testing could serve as a marker for the benefit of immunization with paternal leukocytes; the subsequent presence as a prognostic marker for the subsequent pregnancy.

Abortion, Habitual↗

PubMed1999

Macrophage infiltration and angiogenesis in cervical squamous cell carcinoma--clinicopathologic correlation.

BACKGROUND: The role of angiogenesis and inflammatory cell response in predicting disease outcome was evaluated in various malignant tumors. However, the data relating to cervical cancer remains equivocal. This study evaluates the prognostic significance of microvessel counts and peritumoral macrophage infiltrates in squamous cell carcinoma of the uterine cervix. METHODS: Seventy-five cervical squamous cell carcinomas were stained immunohistochemically by two endothelial markers- anti-CD31 and Ulex Europaeus lectin I (UEA-I), and the macrophage- specific marker anti-CD68. Microvessel and macrophage counts were performed using a grid at X200 and X400 magnification, respectively, in areas of maximal density ('hot spots'). Five fields were scanned. Microvessel counts were correlated with macrophage density, and both were correlated with patient age, tumor stage, histological grade, and survival. RESULTS: Microvessel counts were comparable for ulex lectin (mean 6.8+/-4.8/field) and CD31 (8.7+/-5.3/field), and results by both markers correlated (p<0.001). Counts by both markers correlated with tumor stage, being higher in stages Ib-II compared to stage III-IV tumors (p<0.05). No correlation with age, grade, or survival was found. Macrophage counts (mean 13.1+/-12.3 cells/field) did not correlate with any of the clinical parameters studied or with microvessel counts. CONCLUSIONS: Microvessel counts and macrophage density do not correlate with survival in cervical cancer. Neither do they appear to be inter-related. The association between elevated microvessel counts and localized disease may reflect peak angiogenic stimuli by neoplastic cells. We hypothesize that the beneficial role of macrophages in cellular immunity may be opposed by the elaboration of growth factors in the vicinity of neoplastic cells.

Adult↗

PubMed1998

Rates of Jewish ancestral mutations in BRCA1 and BRCA2 in borderline ovarian tumors.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are known to be associated with an increased risk of breast and epithelial ovarian cancers. Two specific mutations, 185delAG-BRCA1 and 6174delT-BRCA2, have been detected in a substantial proportion (20%-60%) of unselected Ashkenazi Jewish patients--i.e., Jewish patients of Eastern/Northern European descent--with invasive ovarian cancer and in a measurable proportion (2%) of the general Ashkenazi Jewish population. However, uncertainty exists concerning the heritable basis of borderline ovarian tumors and whether these tumors represent an early form of ultimately invasive disease. To gain insight into these issues, we determined the rates of 185delAG-BRCA1 and 6174delT-BRCA2 mutations in patients with borderline ovarian tumors. METHODS: Analysis of 185delAG-BRCA1 and 6174delT-BRCA2 germline mutations was performed by use of a heteroduplex formation assay in samples from 46 consecutive patients with borderline ovarian tumors and 59 consecutive patients with invasive epithelial ovarian cancers. Forty-eight samples were also analyzed by restriction enzyme analysis for the presence of the 5382insC-BRCA1 mutation, a mutation detected in 2.2% of Ashkenazi Jewish patients with breast, but not ovarian, cancer. RESULTS: One (2.2%) of the 46 patient with borderline tumors was identified as a carrier of the 185delAG-BRCA1 mutation, and no patients were found to carry the 6174delT-BRCA2 mutation. Nineteen (32%) of the 59 patients with invasive ovarian cancer were found to carry one of these two mutations; 17 carried 185delAG-BRCA1 and two carried 6174delT-BRCA2 (chi2 test with continuity correction, P = .00028). None of the patients analyzed for 5382insC-BRCA1 were found to carry the mutation. In one high-risk family that included 185delAG-BRCA1 carriers, a single patient with stage IIIc borderline ovarian tumor did not carry the mutation. CONCLUSIONS: Invasive epithelial and borderline ovarian tumors appear to differ in their genetic predisposition and in the molecular mechanisms underlying their genesis.

Female↗