Concordance and clinical significance of uncommon variants of bladder urothelial carcinoma in transurethral resection and radical cystectomy specimens.

OBJECTIVE: To evaluate the concordance and prognostic role of histologic variants of bladder urothelial carcinoma in transurethral resection of bladder tumor (TURBT) and radical cystectomy (RC) specimens. METHODS: Clinicopathologic information available at the time of RC and follow-up data from 4110 RC specimens, collected between January 2000 and December 2009 at 17 tertiary referral centers were retrospectively analyzed and evaluated for the presence or absence of uncommon variants of bladder urothelial carcinoma. The presence or absence of uncommon variants of bladder urothelial carcinoma was evaluated on previous TURBT specimens of patients undergoing RC. Cox regression was used to assess the impact of these parameters on cancer-specific survival, and the Kaplan-Meier test for disease-free survival was plotted for survival estimate. RESULTS: Of 4110 patients, 579 were found to have uncommon variants of bladder urothelial carcinoma at RC (14.1%), whereas 266 (6.4%) at TURBT. A lack of agreement about uncommon variants was observed between TURBT and RC specimens in the entire population (P <.001). The presence of uncommon variants at TURBT was associated with an increased risk of pathologic upstage (hazard ratio, 3.24; confidence interval, 1.19-6.37; P <.003) and significant decrease in cancer-specific survival and recurrence-free survival (P <.001). CONCLUSION: Although the concordance of presence of uncommon histologic variants of urothelial bladder carcinoma between TURBT and RC is low, the presence of uncommon histologic variants of urothelial bladder carcinoma at TURBT is associated with a less favorable clinical outcome.

Altered proteolysis in fibroblasts of Alzheimer patients with predictive implications for subjects at risk of disease.

There is great interest in developing reliable biomarkers to support antemortem diagnosis of late-onset Alzheimer's disease (AD). Early prediction and diagnosis of AD might be improved by the detection of a proteolytic dysfunction in extracts from cultured AD fibroblasts, producing altered isoelectrophoretic forms of the enzyme transketolase (TK-alkaline bands). The TK profile and apolipoprotein E (APOE) genotype were examined in fibroblasts from 36 clinically diagnosed probable late-onset sporadic AD patients and 38 of their asymptomatic relatives, 29 elderly healthy individuals, 12 neurological non-AD patients, and 5 early-onset AD patients. TK alterations occurred in (i) several probable AD patients regardless of age-of-onset and severity of disease; (ii) all early-onset AD patients and APOE ε 4/4 carriers; and (iii) nearly half of asymptomatic AD relatives. Normal subjects and non-AD patients were all negative. Notably, culture conditions promoting TK alterations were also effective in increasing active BACE1 levels. Overall, the TK assay might represent a low-cost laboratory tool useful for supporting AD differential diagnosis and identifying asymptomatic subjects who are at greater risk of AD and who should enter a follow-up study. Moreover, the cultured fibroblasts were confirmed as a useful in vitro model for further studies on the pathogenetic process of AD.

Apple consumption is related to better sexual quality of life in young women.

INTRODUCTION: Even if some evidence exists of a positive correlation between regular intake of phytoestrogens, polyphenols, antioxidants and women's sexual health, there is not a study addressing the potential correlation between daily apple consumption and women's sexual function. We aim to assess whether there is a tie between daily apple intake and sexual function in a sample of healthy young sexually active Italian women, not complaining of any sexual disorders. MATERIALS AND METHODS: Seven hundred and thirty-one women (mean age 31.9, range 18-43) were enrolled in this cross-sectional study (from September 2011 to April 2012). All participants completed anonymously the Female Sexual Function Index (FSFI) and were asked to report on their amount of daily apple consumption and their eating habits. On the basis of apple consumption all women were split into two groups: Group A--regular daily apple consumption, Group B--no regular apple consumption (<1 apple/day). The main outcome measure was the FSFI questionnaire result. RESULTS: Three hundred and forty-three women reported a regular daily apple intake and were classified in Group A, while 388 were included in Group B. Group A had a significantly higher total (p = 0.001; Cohen's d = 3.39) and lubrication domain (p = 0.001; Cohen's d = 3.02) FSFI scores than participants in Group B. Multivariate analysis demonstrated that daily apple intake must be considered as an independent parameter (p = 0.002) in predicting a better score at questionnaire examination. DISCUSSION: This study suggests a potential relationship between regular daily apple consumption and better sexuality in our young women population.

COUP-TFII in pancreatic adenocarcinoma: clinical implication for patient survival and tumor progression.

Despite the accumulating knowledge of alterations in pancreatic cancer molecular pathways, no substantial improvements in the clinical prognosis have been made and this malignancy continues to be a leading cause of cancer death in the Western World. The orphan nuclear receptor COUP-TFII is a regulator of a wide range of biological processes and it may exert a pro-oncogenic role in cancer cells; interestingly, indirect evidences suggest that the receptor could be involved in pancreatic cancer. The aim of this study was to evaluate the expression of COUP-TFII in human pancreatic tumors and to unveil its role in the regulation of pancreatic tumor growth. We evaluated COUP-TFII expression by immunohistochemistry on primary samples. We analyzed the effect of the nuclear receptor silencing in human pancreatic cancer cells by means of shRNA expressing cell lines. We finally confirmed the in vitro results by in vivo experiments on nude mice. COUP-TFII is expressed in 69% of tested primary samples and correlates with the N1 and M1 status and clinical stage; Kaplan-Meier and Cox regression analysis show that it may be an independent prognostic factor of worst outcome. In vitro silencing of COUP-TFII reduces the cell growth and invasiveness and it strongly inhibits angiogenesis, an effect mediated by the regulation of VEGF-C. In nude mice, COUP-TFII silencing reduces tumor growth by 40%. Our results suggest that COUP-TFII might be an important regulator of the behavior of pancreatic adenocarcinoma, thus representing a possible new target for pancreatic cancer therapy.

The role of asymptomatic bacteriuria in young women with recurrent urinary tract infections: to treat or not to treat?

BACKGROUND: Little is known about the role of asymptomatic bacteriuria (AB) treatment in young women affected by recurrent urinary tract infection (UTI). We aimed to evaluate the impact of AB treatment on the recurrence rate among young women affected by recurrent UTI. METHODS: A total of 673 consecutive asymptomatic young women with demonstrated bacteriuria from January 2005 to December 2009 were prospectively enrolled. Patients were split into 2 groups: not treated (group A, n = 312) and treated (group B, n = 361). Microbiological and clinical evaluations were performed at 3, 6, and 12 months. Quality of life was also measured. Recurrence-free rate at the end of the entire study period was the main outcome measure. RESULTS: At baseline, the 2 most commonly isolated pathogens were Escherichia coli (group A, 38.4%; group B, 39.3%) and Enterococcus faecalis (group A, 32.7%; group B, 33.2%). At the first follow-up visit, there was no difference between the 2 groups (relative risk [RR], 1.05; 95% confidence interval [CI], 1.01-1.10), whereas after 6 months, 23 (7.6%) in group A and 98 (29.7%) in group B showed recurrence with a statistically significant difference (RR, 1.31; 95% CI, 1.21-1.42; P < .0001). At the last follow-up, 41 (13.1%) in group A and 169 (46.8%) in group B showed recurrence (RR, 3.17; 95% CI, 2.55-3.90; P < .0001). One patient in group A and 2 patients in group B were found to have pyelonephritis. CONCLUSIONS: This study shows that AB should not be treated in young women affected by UTI, suggesting it may play a protective role in preventing symptomatic recurrence.

Epidemiological features and resistance pattern in uropathogens isolated from chronic bacterial prostatitis.

Chronic bacterial prostatitis (CBP) is, usually, caused by uropathogens, especially gram-negative bacilli, although infection is sometimes due to Gram-positive and atypical microorganisms. A recent increasing in prevalence of Gram-positive strains has been reported. The aim of this study was to explore the epidemiological features and resistance rates in uropathogens isolated from CBP outpatients in last 10 years. All consecutive outpatients with demonstrated CBP attending a single Sexually Transmitted Disease centre from January 1997 and December 2008, were enrolled and underwent microbiological cultures in first void early morning urine, midstream urine, expressed prostatic secretion, and post prostate massage urine. Prevalence of different bacterial strains was stratified in four different periods: 1997-1999, 2000-2002, 2003-2005, 2006-2008. Any changes observed in epidemiological features and resistance rates in uropathogens over the whole study period have been analyzed. The present study has been planned, thus, as in vitro study. From 6,221 patients, 4,601 Gram-positive and 1,620 Gram-negative bacterial strains have been isolated. Enterococcus faecalis and Escherichia coli strains are the first and second frequent pathogens found, respectively. Significant differences between E. faecalis prevalence in the 1997-1999 and 2006-2008 periods were found. E. coli showed a significant difference between prevalence in 1997-1999 and 2006-2008 periods. Gram-positive organisms showed a decreasing of susceptibility to ciprofloxacin as well as Gram-negative strains, while a good susceptibility to the levofloxacin was evidenced. E. faecalis prevalence seemed to be raised in 2006-2008 periods. Moreover, a decreasing of activity of ciprofloxacin and a good activity profile of levofloxacin have been reported.

Genital Chlamydia trachomatis infection is related to poor sexual quality of life in young sexually active women.

INTRODUCTION: Chlamydia trachomatis (Ct) genital infection has been related to several diseases in young sexually active women. It could be related to their sexual quality of life. AIM: To assess whether genital Ct infection can induce sexual function alterations in women. METHODS: Nine hundred ninety-eight women (mean age 29.4, range 18-43) attending our Sexually Transmitted Disease Centre were enrolled in this observational case-control study. All participants were clinically and microbiologically investigated due to their sexual relationships with a subject affected by chronic bacterial prostatitis. All participants underwent microbiological cultures, DNA and antibodies evaluation for common bacteria and Ct on vaginal swab and urine samples. They completed the Female Sexual Function Index [FSFI] questionnaire. On the basis of microbiological investigation results, all patients were split into three groups: Group A-genital Ct infection, Group B-genital common bacteria/yeast infection, and Group C-negative for Ct and bacteria/yeast infection. MAIN OUTCOME MEASURES: FSFI questionnaire. RESULTS: Two hundred ninety-one women were classified in Group A, 276 in Group B, and 431 in Group C. Group A patients were statistically, significantly different from Group B and Group C patients in terms of pain during sexual intercourse and sexual satisfaction. Group C patients had significantly higher FSFI scores (27.1 ± 1.3) (P < 0.001) for both desire (4.9 ± 1.0) and lubrication domain (3.8 ± 1.1) (P < 0.001, P < 0.003, respectively) when compared with Group A patients. Multivariate analysis demonstrated that negative Ct infection marker in female patients must be considered as an independent prognostic factor in predicting a subsequent optimal FSFI questionnaire score (P = 0.002). CONCLUSIONS: Positive values of Ct infection markers are associated with lower FSFI scores for sexual desire, lubrication, and overall sexual function. Genital Ct infection could induce pain during sexual intercourse, reducing sexual satisfaction and sexual quality of life in young sexually active women.

[Oral vitamin B12: Efficacy and safety data in 31 patients with pernicious anemia and food-cobalamin malabsorption]. / Efficacité et tolérance de la vitamine B12 par voie orale chez 31 patients avec une maladie de Biermer ou une maldigestion des cobalamines alimentaires.

OBJECTIVE: The aim of this study is to validate the efficacy and safety of oral cobalamin therapy in the treatment of cobalamin deficiency related to various causes. PATIENT AND METHOD: It's a retrospective study, including 31 patients with documented cobalamin deficiency related to food-cobalamin malabsorption (n=20) and pernicious anemia (n=11). These patients were treated at least for 3 months with oral cyanocobalamin, between 125 to 1000microg per day. Serum cobalamin levels and hematological parameters were compared before and after the therapy and in relation with the nature of cobalamin deficiency. Safety data were also recorded. RESULTS: After 3 months of therapy, the serum cobalamin levels have significantly increased in all the patients, with a mean of +161.6±79.3pg/mL in the food-cobalamin malabsorption group (P<0,00005) and +136.7±67.4pg/mL in the pernicious anemia group (P<0,0001). Hematological parameters have been normalized in 90 % of the patients, independently of the cause of the cobalamin deficiency. Only 1 patient presented an urticarial reaction. CONCLUSION: This study confirms the efficacy and safety of oral cobalamin therapy in food-cobalamin malabsorption and also in case of pernicious anemia.

Fast-track surgery after laparoscopic colorectal surgery: is it feasible in a general surgery unit?

BACKGROUND: The aim of the "fast-track surgery" program is to decrease the peri-operative stress response to surgical trauma and thus to a decrease in complication rates after elective surgery. Critics of fast-track (FT) rehabilitation may argue that all reports of successful programs came from major specialized hospital units and that implementation in smaller or less specialized units may be difficult if not impossible. METHODS: We retrospectively studied 101 patients who, from November 2004 to October 2007, underwent laparoscopic colorectal surgery in our institute. A detailed FT surgery protocol had been prepared and given to patients, physicians and nurses, with the aim to create a standard treatment. Data about demographics, ASA score, pre-operative complicating diseases, diagnosis, type of surgery, and postoperative clinical data were analyzed. Univariate analysis of the relationship between all factors (patient characteristics, intervention characteristics, protocol compliance and presence of complications) described here and length of hospital stay was performed. RESULTS: We compared our results to published major trials and observed no substantial differences in morbidity, mortality and length of postoperative hospital stay between the 2. Univariate analysis showed that compliance to the elements of the FT protocol influences the length of postoperative period more significantly than patient characteristics or surgical procedure. CONCLUSION: Based on 6 comparative single-center studies, the FT program was found to reduce length of hospital stay, and was deemed safe for major abdominal surgeries. Present study shows that enhanced recovery or FT program can also be implemented safely in a general surgery unit.

Regular moderate intake of red wine is linked to a better women's sexual health.

INTRODUCTION: While some evidence does exist for a positive correlation between moderate wine intake and men's sexual health, there is no study addressing the potential correlation between red wine intake and women's sexual function. AIM: The aim of our study was to assess whether there is a tie between daily red wine intake and sexual function in a sample of healthy Italian women, living in the Chianti area (Tuscany) not complaining of any sexual disorders. METHODS: We recruited 798 women (age 18-50), living in the Chianti area (Tuscany), not complaining of any sexual disorders. We divided the participants into three groups: daily moderate (one to two glasses) red wine intake (group 1); teetotallers (group 2); and daily intake of more than two glasses of red wine and/or other types of alcoholic drinks (including white wine), as well as of those reporting occasional drinking (group 3). MAIN OUTCOME MEASURES: All participants completed anonymously the Female Sexual Function Index (FSFI) questionnaire and were asked to report on their amount and type of alcohol consumption. RESULTS: Group 1 had significantly higher total (P = 0.001), as well as desire and lubrication domain (P = 0.001 and P = 0.001, respectively) FSFI scores than participants in groups 2 and 3. No significant differences between the groups were observed concerning sexual arousal, satisfaction, pain, and orgasm. Univariate analysis showed a significant correlation between age, alcohol consumption (P = 0.009), and a better score at questionnaire examination. During multivariate analysis, alcohol consumption was identified as an independent prognostic parameter (P = 0.002) in predicting the better score at questionnaire examination. CONCLUSIONS: The finding that regular moderate intake of red wine is associated with higher FSFI scores for both sexual desire, lubrication, and overall sexual function as compared to the teetotaller status is intriguing. While this finding needs to be interpreted with some caution, because of the small sample size, self-reported data, and the lack of support from laboratory exams, it nevertheless suggests a potential relationship between red wine consumption and better sexuality.

Estrogen receptor expression in cutaneous melanoma: a real-time reverse transcriptase-polymerase chain reaction and immunohistochemical study.

OBJECTIVE: To evaluate estrogen receptor (ER) expression in human melanoma tissues and in the adjacent healthy skin with the aim of explaining whether the ERalpha:ERbeta expression ratio has a role in neoplastic progression. DESIGN: Prospective study. SETTING: Department of Dermatology, University of Florence, Florence, Italy. Patients Fourteen patients, 12 with cutaneous melanoma (6 women and 6 men) and 2 with melanocytic nevi (1 woman and 1 man). MAIN OUTCOME MEASURES: Using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analysis, we analyzed ERalpha and ERbeta messenger RNA (mRNA) and ERbeta protein expression in cutaneous melanoma and in the healthy skin surrounding the lesions. RESULTS: All melanocytic lesions expressed detectable levels of ERalpha and ERbeta mRNA as well as ERbeta protein. Dividing melanoma cases into 2 groups according to Breslow thickness, we found lower ERalpha and ERbeta mRNA levels and lower ERbeta protein levels in thicker, more invasive tumors. CONCLUSIONS: These observations suggest a role for ERs in the metastatic process of melanoma cells, pointing at the possibility of using ERbeta expression as a prognostic indicator of melanoma. The possibility of distinguishing proliferative melanomas, which are associated with dismal prognosis, from the so-called dormant melanomas opens up novel avenues in tailoring individual treatments, as already happens for other tumors.

Pathology of the thoracic aorta: a morphologic review of 338 surgical specimens over a 7-year period.

A total of 338 surgical specimens of the thoracic aorta were studied morphologically. These were obtained from patients (238 males, 100 females) operated on for aortic aneurysm or dissection at the Careggi Hospital, Florence, Italy, between January 1999 and June 2005. Medial degeneration was diagnosed in 299 cases (138 aneurysms, 161 dissections), atherosclerosis with extensive medial destruction was seen in 32 cases (26 aneurysms, 6 dissections), and giant cell arteritis (GCA) was found in 7 cases (all aneurysms). These data show that medial degeneration was a common nonspecific histologic diagnosis in aortic resection after the occurrence of aneurysm or dissection. Considering that this diagnosis was made in as many as 118 patients over 70 years of age and in 175 patients over 65, normal advancing age would appear as the most frequent correlation with these aortic events. Ageing is also associated with the increasing number of cases of GCA with aortic involvement. Angiogenesis, always observed next to areas of medial damage whatever the underlying pathology, may contribute to the pathogenesis of aortic dissection and aneurysm.

Vitamin D receptor alleles and C-reactive protein in hemodialysis patients.

Cardiovascular disease due to atherosclerosis is the major determinant of morbidity and mortality in uremic patients. Inflammation is essential in the development of atherosclerosis and markers of inflammation, in particular C-reactive protein, predict the cardiovascular risk. Vitamin D exerts its effects through the Vitamin D Receptor, coded for by a gene showing several polymorphisms associated with a variety of diseases and differential responses to Vitamin D. We evaluated the association between four Vitamin D Receptor polymorphisms (i.e. those identified by the restriction enzymes BsmI, ApaI, TaqI and FokI) and serum level of C-reactive protein in 88 hemodialysis patients routinely treated with active Vitamin D (calcitriol). Absence or presence of the BsmI, ApaI, TaqI, and FokI restriction sites were denominated B and b, A and a, T and t, F and f respectively. Our results show that the b, a, T, alleles were more frequent in patients with elevated serum level of C-reactive protein compared with patients with normal C-reactive protein level. The differences were statistically significant (p < 0.05). These results suggest that the Vitamin D Receptor alleles b, a, T could be considered novel risk factors in the pathogenesis of inflammation-related, atherosclerosis-dependent cardiovascular disease risk in uremic patients.

Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study.

PURPOSE: We evaluated the impact of epirubicin perioperative instillation in improving subsequent bacillus Calmette-Guerin instillation efficacy in high risk patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Between January 2005 and June 2007, 161 patients affected by high risk nonmuscle invasive bladder cancer were enrolled in this prospective, randomized, controlled, double-blind study. A total of 80 patients were assigned to group A (perioperative epirubicin 80 mg/50 ml normal saline) plus delayed bacillus Calmette-Guerin instillations (5 x 108 colony-forming units in 50 ml saline) and 81 to group B (delayed bacillus Calmette-Guerin alone). The main outcome measures were time to first recurrence and recurrence rate. All data obtained from a median followup of 15.3 months in group A and 14.8 months in group B, were analyzed. RESULTS: At the end of followup 46 of 80 patients in group A (57.5%) had no evidence of disease, just like 41 of 81 in group B (50.6%). No statistical difference was observed between the 2 groups in terms of recurrence rate (p = 0.82) or time to first recurrence (p = 0.095). Kaplan-Meier analysis of recurrence showed no significant differences between group A and group B (p = 0.0952). On multivariate analysis the early single dose instillation of epirubicin was not indicated as an independent prognostic factor (HR 0.50, 95% CI 0.32-1.18). CONCLUSIONS: The present study showed no statistically significant differences in terms of disease-free time and recurrence rate between high risk patients with nonmuscle invasive bladder cancer who had undergone perioperative epirubicin instillation plus delayed bacillus Calmette-Guerin and those who had undergone delayed bacillus Calmette-Guerin alone.

Acute viral hepatitis increases liver stiffness values measured by transient elastography.

Liver tissue alterations other than fibrosis may have an impact on liver stiffness measurement. In this study we evaluated 18 patients without a previous clinical history of liver disease, consecutively admitted for acute viral hepatitis. In each patient, aminotransferase determination and liver stiffness measurement were performed on the same study day, at 3 different points: (1) peak increase in aminotransferase; (2) aminotransferase 50% or less of the peak; (3) aminotransferase levels

Psychomotor, cognitive and social interactions in elderly and old Italians. Preliminary report.

It was the aim of this pilot study to investigate effects of motor activity on psychosocial and functional-physical conditions (using an assisted multidimensional questionnaire) of 53 (39 female, 14 male) free living elderly and old subjects in Florence, Italy. In addition, ADL (test of Activities of Daily Living) and Pfeiffer test (short portable mental status questionnaire) were applied to test autonomy of everyday life and presence of intellectual disturbance of organic origin. Motor activity appeared to influence significantly psychosocial and functional-physical conditions, i. e. motor activity was significantly correlated with subjective feeling of autonomy and independence, and with the variable to have hobbies, as well as with good posture and walking. From ADL and Pfeiffer tests resulted absence of respective pathologies.

Prevalence, incidence estimation, risk factors and characterization of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy: results of a multicenter case-control observational study.

PURPOSE: We evaluated the prevalence and estimated the incidence and risk factors of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy. MATERIALS AND METHODS: From January to June 2006 patients from 28 Italian urological centers who were between 25 and 50 years old with symptoms of chronic prostatitis/chronic pelvic pain syndrome were consecutively enrolled in this prospective epidemiological case-control study. A total of 152 subjects of similar age, race and area of origin who were investigated for infertile couples but were otherwise healthy served as controls. All subjects provided a medical history and underwent different symptom scorings, clinical evaluation and microbiological tests. RESULTS: Of 5,540 male urological outpatients 764 with chronic prostatitis/chronic pelvic pain syndrome were enrolled, including 225 (29.4%) at the first presentation and 539 (70.6%) who underwent previous treatment. Thus, the prevalence of the syndrome was 13.8%, while the estimated incidence was 4.5%. Cigarette smoking, a high caloric diet with low fruit and vegetable consumption, constipation, meteorism, slow digestion, a sexual relationship with more than 1 partner and coitus interruptus were more likely in patients with chronic prostatitis/chronic pelvic pain syndrome than in controls (each p <0.001). The syndrome had a negative influence on sexual desire, erectile dysfunction and premature ejaculation (p <0.001). The Meares and Stamey test was positive in 13.3% of patients and in 2.9% of controls. Urethral swabs in patients with a negative Meares and Stamey test were positive for sexually transmitted pathogens in 6%. CONCLUSIONS: The prevalence and estimated incidence of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy are high. The syndrome is closely related to lifestyle, diet, smoking, gastrointestinal or anorectal disease and impaired sexual function.

Liquid-based endometrial cytology in the management of sonographically thickened endometrium.

Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures.

VEGFR-1 (FLT-1), beta1 integrin, and hERG K+ channel for a macromolecular signaling complex in acute myeloid leukemia: role in cell migration and clinical outcome.

Leukemia cell motility and transendothelial migration into extramedullary sites are regulated by angiogenic factors and are considered unfavorable prognostic factors in acute leukemias. We have studied cross talk among (1) the vascular endothelial growth factor receptor-1, FLT-1; (2) the human eag-related gene 1 (hERG1) K(+) channels; and (3) integrin receptors in acute myeloid leukemia (AML) cells. FLT-1, hERG1, and the beta(1) integrin were found to form a macromolecular signaling complex. The latter mostly recruited the hERG1B isoform of hERG1 channels, and its assembly was necessary for FLT-1 signaling activation and AML cell migration. Both effects were inhibited when hERG1 channels were specifically blocked. A FLT-1/hERG1/beta(1) complex was also observed in primary AML blasts, obtained from a population of human patients. The co-expression of FLT-1 and hERG1 conferred a pro-migratory phenotype to AML blasts. Such a phenotype was also observed in vivo. The hERG1-positive blasts were more efficient in invading the peripheral circulation and the extramedullary sites after engraftment into immunodeficient mice. Moreover, hERG1 expression in leukemia patients correlated with a higher probability of relapse and shorter survival periods. We conclude that in AML, hERG1 channels mediate the FLT-1-dependent cell migration and invasion, and hence confer a greater malignancy.

Pathologic determinants of survival after resection of T3N0 (Stage IIA) colorectal cancer: proposal for a new prognostic model.

PURPOSE: There is an increasing need for accurate prognostic stratification of patients with Stage II colorectal cancer to identify a subgroup of high-risk patients who may benefit from adjuvant therapies. This study was designed to evaluate the prognostic impact of a wide spectrum of pathologic parameters in a consecutive series of homogenously treated and well-characterized patients with Stage IIA (T3N0M0) colorectal cancer. METHODS: The study included 238 patients operated on by a single surgeon for Stage IIA colorectal tumors. The median postoperative follow-up was 110 (range, 96-120) months. At least 12 lymph nodes were harvested and examined in all the resection specimens. The prognostic value of 13 pathologic parameters, including lymph node occult disease (micrometastases) detected by immunohistochemistry, was investigated. RESULTS: Multivariate analysis identified tumor growth pattern (expanding or infiltrating; P = 0.01) and extent of tumor spread beyond muscularis propria (< or =5 mm or >5 mm; P = 0.04) as the only factors having independent prognostic value. The combination of these two easily determined parameters allowed us to identify two groups of patients at low risk or high risk of tumor recurrence. The eight-year survival rates were 83.3 and 53.4 percent for the two groups, respectively. The high-risk group comprised those patients with infiltrating tumors and extramural tumor spread > 5 mm. CONCLUSIONS: We propose a new and simple prognostic model to identify patients with high-risk Stage IIA colorectal cancer for whom adjuvant therapies may be justified and effective.