Potential roles of Helicobacter pylori treatment, body mass index and waist circumference in the causation of erosive esophagitis: a randomized clinical trial (HEROES-GERD).

BACKGROUND: In recent decades, the prevalence of gastroesophageal reflux disease (GERD) and obesity has been increasing while Helicobacter pylori infection has been decreasing. OBJECTIVE: To evaluate if H. pylori treatment, excess body weight and other anthropometric measurements are associated with incident erosive esophagitis, as a secondary objective of a trial which tested the efficacy of treatment of H. pylori on the symptoms of functional dyspepsia. SUBJECTS/METHODS: Upper gastrointestinal endoscopy and anthropometric assessments were performed, at baseline and after 12 months, in H. pylori positive patients with functional dyspepsia who had no baseline reflux symptoms or esophagitis. Patients were randomly assigned to receive omeprazole, amoxicillin, and clarithromycin (antibiotic group; n = 201) or omeprazole plus placebo (control group; n = 203). The primary outcome was the incidence of esophagitis 12 months after randomization, according to treatment groups, and the association of BMI and other anthropometric measurements. RESULTS: Four hundred and four patients were included (mean age, 46.1 years; 78.7% women). The 12-month follow-up endoscopic esophagitis rates for the antibiotic and control groups were 10.9% (22/201) and 9.4% (19/203), respectively (p = 0.60). The number needed to harm was 67. Baseline anthropometric measurements were performed in 94% (380/404) of patients. The 12-month follow-up esophagitis rates for overweight and normal body weight patients were 13.6% (29/213) and 6.0% (10/167), respectively (p = 0.015); rates for patients with and without increased baseline waist circumference were 15.4% (24/156) and 6.7% (15/224), respectively (p = 0.006). Following logistic regression, only the combination of increased baseline body mass index and waist, but not H. pylori treatment, was independently associated with new-onset esophagitis (OR 2.88; 95% CI: 1.28-6.45). CONCLUSIONS: Excess body weight and concomitant increased waist circumference, but not H. pylori treatment, predicts new-onset esophagitis.

Study on the organization of cellular elements in the granulomatous lesion caused by chromoblastomycosis.

BACKGROUND: Chromoblastomycosis is a deep fungal infection characterized by a complex cellular granuloma. The aim of this study was to analyze the arrangement of cells responsible for the granuloma configuration of this disease by semiquantification of the cellular components of chromoblastomycosis skin biopsies. METHODS: The cells of cutaneous biopsies slides from 100 patients with untreated chromoblastomycosis were stained with hematoxylin-eosin and the granuloma cells were evaluated by microscopic examination of the elements of each granuloma and semiquantified the number of cells through its expressivity in crosses and the histopathological variables. Their presence were coded in degrees of intensity and classified in two categories: low expression and high expression. The cells that constituted the granulomas were separated into three groups: A, B and C. RESULTS: The chromoblastomycotic granuloma analyzed by this semiquantification of its cellular components showed that there was high expression of the elements setting up a mixed organized mycotic granuloma. It was observed that mononuclear phagocytic system (A), polymorphonuclear phagocytic system (B) and lymphoplasmocytic infiltrate (C) were located around the fungus. CONCLUSION: The results indicated that the granuloma present in the cutaneous lesion of chromoblastomycosis is a mixed organized mycotic granuloma with high expression of the cellular components.

Long-Term Comparison of Aesthetical Outcomes After Oncoplastic Surgery and Lumpectomy in Breast Cancer Patients.

BACKGROUND: Lumpectomy may result in major deformities and asymmetries in approximately one-third of patients. Although oncoplastic surgery (OP) could be a useful alternative to avoid them, lack of strong data is causing some debate. The purpose of this study was to compare aesthetic outcomes in patients undergoing OP versus lumpectomy using three different assessment methods. METHODS: A total of 122 patients were included in this cross-sectional multicentric study; 57 underwent OP (46.7 %), and 65 underwent lumpectomy (53.3 %). Two breast surgeons and two plastic surgeons from different institutions using the Garbay scale independently evaluated aesthetic outcomes. BCCT.core software was applied in both groups, and the patients evaluated their aesthetic outcomes answering a questionnaire about their satisfaction rate. RESULTS: OP group had a higher proportion of excellent aesthetic results according to the BCCT.core software analysis (p = 0.028) and the specialists (p = 0.002). Multifactorial analyses showed that age ≥70 years (RP = 6.02; 95 % confidence interval [CI] 1.73-21.0; p = 0.005), tumors in the medial, inferior, and central quadrants (RP = 4.21; 95 % CI 1.88-9.44; p < 0.001), and large breasts (RP = 7.55; 95 % CI 2.48-23.0; p < 0.001) were significant risk factors for poor aesthetic outcomes after lumpectomy. The patients classified their results as better than those by the specialists and by the software, with no statistical difference between the groups. CONCLUSIONS: Excellent aesthetic results were more frequent in the OP group according to BCCT.core software analysis and specialists. In addition, some clinical conditions and tumor locations in the breast can be considered risky factors for poor aesthetic outcomes in lumpectomy.

NTPDase3 and ecto-5'-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression.

According to the World Health Organization, bladder cancer is the seventh most common cancer among men in the world. The current treatments for this malignancy are not efficient to prevent the recurrence and progression of tumors. Then, researches continue looking for better therapeutic targets which can end up in new and more efficient treatments. One of the recent findings was the identification that the purinergic system was involved in bladder tumorigenesis. The ectonucleotidases, mainly ecto-5'-nucleotidase/CD73 have been revealed as new players in cancer progression and malignity. In this work, we investigated the NTPDase3 and ecto-5'-nucleotidase/CD73 expression in cancer progression in vivo. Bladder tumor was induced in mice by the addition of 0.05 % of N-butyl-N-(hydroxybutyl)-nitrosamine (BBN) in the drinking water for 4, 8, 12, 18, and 24 weeks. After this period, mice bladders were removed for histopathology analysis and immunofluorescence assays. The bladder of animals which has received BBN had alterations, mainly inflammation, in initial times of tumor induction. After 18 weeks, mice's bladder has developed histological alterations similar to human transitional cell carcinoma. The cancerous urothelium, from mice that received BBN for 18 and 24 weeks, presented a weak immunostaining to NTPDase3, in contrast to an increased expression of ecto-5'-nucleotidase/CD73. The altered expression of NTPDase3 and ecto-5'-nucleotidase/CD73 presented herein adds further evidence to support the idea that alterations in ectonucleotidases are involved in bladder tumorigenesis and reinforce the ecto-5'-nucleotidase/CD73 as a future biomarker and/or a target for pharmacological therapy of bladder cancer.

Ectonucleotidases in tumor cells and tumor-associated immune cells: an overview.

Increasing evidence points out that genetic alteration does not guarantee the development of a tumor and indicates that complex interactions of tumor cells with the microenvironment are fundamental to tumorigenesis. Among the pathological alterations that give tumor cells invasive potential, disruption of inflammatory response and the purinergic signaling are emerging as an important component of cancer progression. Nucleotide/nucleoside receptor-mediated cell communication is orchestrated by ectonucleotidases, which efficiently hydrolyze ATP, ADP, and AMP to adenosine. ATP can act as danger signaling whereas adenosine, acts as a negative feedback mechanism to limit inflammation. Many tumors exhibit alterations in ATP-metabolizing enzymes, which may contribute to the pathological events observed in solid cancer. In this paper, the main changes occurring in the expression and activity of ectonucleotidases in tumor cells as well as in tumor-associated immune cells are discussed. Furthermore, we focus on the understanding of the purinergic signaling primarily as exemplified by research done by the group on gliomas.

Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury.

Gliomas are the most common and devastating type of primary brain tumor. Many non-neoplastic cells, including immune cells, comprise the tumor microenvironment where they create a milieu that appears to dictate cancer development. ATP and the phosphohydrolytic products ADP and adenosine by activating P2 and P1 receptors may participate in these interactions among malignant and immune cells. Purinergic receptor-mediated cell communication is closely regulated by ectonucleotidases, such as by members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, which hydrolyze extracellular nucleotides. We have shown that gliomas, unlike astrocytes, exhibit low NTPDase activity. Furthermore, ATP induces glioma cell proliferation and the co-administration of apyrase decreases progression of injected cells in vivo. We have previously shown that NTPDase2 reconstitution dramatically increases tumor growth in vivo. Here we evaluated whether NTPDase2 reconstitution to gliomas modulates systemic inflammatory responses. We observed that NTPDase2 overexpression modulated pro-inflammatory cytokine production and platelet reactivity. Additionally, pathological alterations in the lungs were observed in rats bearing these tumors. Our results suggest that disruption of purinergic signaling via ADP accumulation creates an inflammatory state that may promote tumor spread and dictate clinical progression.

Effectiveness of risk-reducing salpingo-oophorectomy in preventing ovarian cancer in a high-risk French Canadian population.

BACKGROUND: Women with germ line BRCA1 or BRCA2 mutations have a marked increased risk of breast and ovarian cancer compared with the general population, whereas risk-reducing salpingo-oophorectomy (RRSO) significantly lowers the incidence of these cancers. The objective of this study was to review the clinical and pathological characteristics of a French Canadian population undergoing RRSO. Surgical morbidity was also evaluated. MATERIALS AND METHODS: From December 1999 to December 2009, all women who underwent RRSO at our institution were identified. Medical records were retrospectively reviewed. Descriptive statistics, the Fischer exact test, and the Student t test were used for analysis. RESULTS: During the study period, RRSO was performed on 119 women. Mean age at surgery was 49 years (35-72 years), and 63 patients (53%) were premenopausal. Sixty-two women (52%) had a history of in situ or invasive breast cancer. BRCA1 and BRCA2 mutations were present in 34 patients (29%) and 42 patients (35%), respectively, whereas 43 patients (36%) were considered to have an increased risk of breast and ovarian cancer, despite a personal genetic test, which was either negative (n = 23) or unknown because the patient declined genetic testing (n = 20). Most patients with a uterus in place had a complementary hysterectomy (65%). Six complications occurred (3 hematomas, 2 cardiac arrhythmias, and 1 cystotomy). In one patient (0.8%), a high-grade stage II ovarian cancer was discovered at the time of surgery. Fallopian tube atypias were identified on final pathology in 8 cases (6.7%). After a median follow-up of 22 months, 4 women (3.4%) developed breast cancer and one woman (0.8%) developed peritoneal cancer. CONCLUSIONS: Risk-reducing salpingo-oophorectomy is highly effective in preventing ovarian, fallopian tube, and breast cancers in a high-risk French Canadian population; and the surgical morbidity is low.

Prevalence of human papillomavirus in breast cancer: a systematic review.

OBJECTIVE: We performed a systematic review and meta-analyses to estimate the prevalence of human papillomavirus (HPV) in breast carcinoma and to explore the reasons for the ongoing controversies about this issue. MATERIALS AND METHODS: A comprehensive search of the Cochrane Library, MEDLINE, CANCERLIT, LILACS, and EMBASE databases was performed for papers published from January 1990 to January 2011. The medical subject heading terms were searched for the following: breast neoplasm, breast lesions, breast cancer, and HPV or human papillomavirus. Statistical analysis was performed using REVMAN 5.0. RESULTS: Twenty-nine primary studies, including 2211 samples, were analyzed. Overall, HPV prevalence in patients with breast cancer was 23.0% (95% CI, 21.2%-24.8%). The prevalence of HPV ranged from 13.4% (95% CI, 10.2%-16%) in Europe to 42.9% (95% CI, 36.4%-49.4%) in North America and Australia. The prevalence of HPV in controls was 12.9%. Combinations of 9 case-control studies showed that breast cancer was associated with HPV (odds ratio, 5.9; 95% CI, 3.26-10.67). CONCLUSION: We found a high prevalence of HPV DNA in breast cancer. There is strong evidence to suggest that HPV has an important role in the development of breast cancer.

Assessment of the Fournier(®) cervical specimen self-sampling device using the Papanicolaou method.

INTRODUCTION: Communities of socially excluded immigrant women, especially Muslim, Asian, Aboriginal and Maroon, are among the groups of women with low rates of cervical screening. Exclusion of the pelvic examination could result in a higher acceptance of the cervical screening among these communities and an increase in screening coverage. AIM: To assess the performance of the Fournier(®) cervical specimen self-sampling device for the cytological diagnosis of precursor or neoplastic lesions in the uterine cervix using the Papanicolaou method. METHODS: A case-control study was conducted at the Cervical Pathology Outpatient Clinic. Liquid-based cytology slides were obtained by the Fournier device and stained using the Papanicolaou method. The slides were analyzed by two pathologists, blinded for the colposcopic and histological results and compared to Papanicolaou smears that were obtained using the traditional method of speculum examination. RESULTS: There were 68 patients who were considered free from precursor or neoplastic cervical lesions. There were 35 cases of low-grade lesions, 13 cases of high-grade lesions and 3 cases of squamous-cell carcinoma. According to the first and second pathologists, the sensitivities of the device for identifying precursor or neoplastic cervical lesions were 50.0 and 60.0%, and the specificities of the method were 81.8 and 73.8%. According to the first and second pathologists, the positive predictive values of the diagnostic test were 0.67 and 0.63, and the negative predictive values were 0.68 and 0.71, respectively. CONCLUSION: Sensitivity and specificity of the Fournier device test was comparable to Papanicolaou smears tests obtained using the traditional method with speculum examination.

Accuracy of magnetic resonance in suspicious breast lesions: a systematic quantitative review and meta-analysis.

Dynamic contrast-enhanced breast magnetic resonance (MR) is a promising emerging technique for evaluating breast lesions. A quantitative systematic review was performed to estimate the accuracy of breast MR in the diagnosis of high-risk breast lesions and breast cancer. A comprehensive search of the Cochrane Library, MEDLINE, CANCERLIT, LILACS, and EMBASE databases was performed from January 1985 to August 2010. The medical subjects heading (MeSH) and text words for the terms "breast neoplasm", "breast lesions", "breast cancer" and "magnetic resonance" were combined with the MeSH term diagnosis ("sensitivity and specificity"). Studies that compared breast MR with paraffin-embedded sections parameters for the diagnosis of breast lesions (benign, high-risk borderline, and breast cancer) were included. Sixty-nine studies were analyzed, which included 9,298 women with 9,884 breast lesions. Interrater overall agreement between breast MR and paraffin section diagnosis was 79% (κ = 0.55), indicating moderate agreement. Pooled sensitivity and specificity were 90% [95% CI 88-92%] and 75% [95% CI 70-79%], respectively. The pooled likelihood positive ratio was 3.64 (95% CI 3.0-4.2) and the negative ratio was 0.12 (95% CI 0.09-0.15). For breast cancer or high-risk lesions versus benign lesions, the AUC was 0.91 for breast MR and the point Q* was 0.84. In summary, breast MR is a useful pre-operative test for predicting the diagnosis of breast lesions.

Prognostic Factors of Long-term Survival Following Radical Resection for Ampullary Carcinoma.

BACKGROUND: The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. METHODS: Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. RESULTS: Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05-6.61; p = 0.039). CONCLUSION: Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.

Aesthetic improvements in Poland's syndrome treatment with omentum flap.

BACKGROUND: There are many techniques that can be used to reconstruct anomalous breast volume in Poland's syndrome, but repair of the stigmatizing deformities such as the transverse skin fold in the anterior axillary pillar, infraclavicular depression, and anomalous breast contours continues to be a challenge. This study aimed to demonstrate the superior results of laparoscopically harvested omentum flap to achieve these aesthetic improvements. METHODS: Patients with Poland's syndrome from a clinical database were identified and their outcomes were studied. RESULTS: In 15 consecutive patients with Poland's syndrome, the breast contour, the anterior axillary pillar, and the infraclavicular depression were treated with omentum flap and evaluated. Silicone implants were used beneath the flap in 80% of cases to improve symmetry. Flap consistency was similar to that of the natural breast and only a small incision in the breast fold was needed. The flap is extremely malleable, adapts to irregular surfaces, and has a long vascular pedicle. It does not leave a scar at the donor site as muscular flaps do. The omentum can repair small irregularities in breast contour, achieving a natural result different from all other flaps. Due to its malleability, it is possible to reconstruct even the extension to the axillary pillar, which is impossible with all other techniques. CONCLUSIONS: The omentum flap technique is a means of repairing the deformities caused by Poland's syndrome and improves the aesthetic result with outcomes that seem superior to any other reconstructive option.

Selective NTPDase2 expression modulates in vivo rat glioma growth.

The ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are a family of ectoenzymes that hydrolyze extracellular nucleotides, thereby modulating purinergic signaling. Gliomas have low expression of all E-NTPDases, particularly NTPDase2, when compared to astrocytes in culture. Nucleotides induce glioma proliferation and ATP, although potentially neurotoxic, does not evoke cytotoxic action on the majority of glioma cultures. We have previously shown that the co-injection of apyrase with gliomas decreases glioma progression. Here, we tested whether selective re-establishment of NTPDase2 expression would affect glioma growth. NTPDase2 overexpression in C6 glioma cells had no effect on in vitro proliferation but dramatically increased tumor growth and malignant characteristics in vivo. Additionally, a sizable platelet sequestration in the tumor area and an increase in CD31 or platelet/endothelial cell adhesion molecule-1 (PECAM-1), vascular endothelial growth factor and OX-42 immunostaining were observed in C6-Enhanced Yellow Fluorescent Protein (EYFP)/NTPDase2-derived gliomas when compared to controls. Treatment with clopidogrel, a P2Y(12) antagonist with anti-platelet properties, decreased these parameters to control levels. These data suggest that the ADP derived from NTPDase2 activity stimulates platelet migration to the tumor area and that NTPDase2, by regulating angiogenesis and inflammation, seems to play an important role in tumor progression. In conclusion, our results point to the involvement of purinergic signaling in glioma progression.

Effect of raloxifene and low-dose percutaneous 17beta-estradiol on menopause symptoms and endometrium--a randomized controlled trial.

OBJECTIVE: To investigate the effects on climacteric symptoms and endometrium of percutaneous low-dose 17beta-estradiol associated with raloxifene in postmenopausal women. DESIGN: randomized placebo-controlled study. METHOD: Fifty-two postmenopausal women with moderate to severe hot flushes were randomized to receive either 60 mg raloxifene (RLX; n=20), 0.5 mg percutaneous 17beta-estradiol associated to 60 mg raloxifene (RLX+E2; n=16) or placebo (PLC; n=16). Climacteric symptoms (Kupperman index) and vaginal bleeding were evaluated. At baseline and at the end of the study endometrial thickness was measured and endometrial samples were collected for histological study. RESULTS: At baseline, the mean Kupperman index was 23.7+/-1.8 in RLX group, 22.9+/-1.9 in RLX+E2 group and 22.6+/-1.9 in the placebo group (NS). After 3 months, there was a significant reduction in Kupperman index mean values in both groups, but no statistical difference was observed between groups. However, RLX+E2 and placebo were significantly superior to RLX in reducing hot flush severity (p<0.05). Endometrial thickness did not change in both groups. The association of percutaneous low-dose 17beta-estradiol to raloxifene was not associated with proliferation of endometrium neither in hysteroscopies nor in endometrial biopsies at the third month of treatment. No vaginal bleeding was reported during the study. CONCLUSIONS: The association of percutaneous low dose of 17beta-estradiol with raloxifene exerted favorable effects on hot flushes severity of postmenopausal women, providing a safe profile in endometrium at least in short-term therapy.

Evaluation of morbidity of suction drains after retroperitoneal lymphadenectomy in gynecological tumors: a systematic literature review.

INTRODUCTION: The prophylactic use of closed suction drains after retroperitoneal lymphadenectomy in the management of gynecologic tumors has been widely used to prevent collections of clots or lymph and to avoid infections and postoperative fistulas. The improvement of newer surgical techniques, the use of antibiotic prophylaxis, and the nonclosure of the peritoneum led to the need to reevaluate the use of drains. Retrospective, prospective, and randomized studies did not find differences in the postoperative morbidity between the use and nonuse of drains. Some studies even suggested worse morbidity with the use of drains. OBJECTIVES: To assess the morbidity of the use of drains compared with no drains in a systematic literature review with aggregate effect measure (meta-analysis). MATERIALS AND METHODS: Between 1966 and August 2007, 3 independent reviewers analyzed all studies that assessed the use of drains or no drains through a comprehensive literature search of the MEDLINE, EMBASE, and Cochrane Central Databases. Statistical analysis was carried out through the RevMan software. RESULTS: Of the 285 studies initially reviewed, 11 were selected. Only 4 were considered adequate for group analysis, totaling 571 patients. When assessing outcomes altogether, namely, fever morbidity, symptomatic lymphocysts, deep vein thrombosis, pelvic infection, and fistulas, the relative risk was 1.76 (95% confidence interval, 1.04-3.01) and number necessary to harm was 12.2 referring to the use of drains. CONCLUSIONS: The prophylactic use of continuous suction drains after retroperitoneal lymphadenectomy in the management of gynecologic tumors should be avoided.

Comparison of loop electrosurgical conization with one or two passes in high-grade cervical intraepithelial neoplasias.

The use of loop electrosurgical conization (LEC) for the treatment of large high-grade cervical intraepithelial neoplasias (CINs) is often associated with a difficult procedure that results in accidental sample fragmentation, thermal damage and sometimes the presence of positive margins. This study aims to compare LEC that removes the cervical cone in two blocks (anterior and posterior cervical lips - LEC2) with LEC performed with one pass of the loop (LEC1). In a randomized, controlled trial, patients that needed conization due to high-grade CIN were assigned to one of the techniques. There were no differences in terms of age, cone histopathological diagnosis, blood loss, vaginal injuries, stenosis of the cervical os and specimen artifacts. LEC2 required less hemostatic sutures. LEC2 showed no specimen fragmentation, while LEC1 did (0 vs. 5.9%; p = 0.10). As expected, LEC2 samples were heavier (p = 0.01), included a larger ectocervical area (p = 0.001) and, therefore, had a greater volume (p < 0.001) compared to LEC1 samples. The height of the LEC2 specimens was smaller than that of LEC1 specimens (p < 0.001). LEC2 yielded fewer cases of positive margins (12.7%) than LEC1 (33.3%; p = 0.021). We conclude that the LEC2 technique is an effective treatment choice: it is safe for the patient, with better outcomes regarding sample quality than LEC1. Further studies are encouraged regarding this procedure.

Up-regulation of VEGF, c-fms and COX-2 expression correlates with severity of cervical cancer precursor (CIN) lesions and invasive disease.

OBJECTIVES: To describe the expression of vascular endothelial growth factor (VEGF), proto-oncogene macrophage colony-stimulating factor receptor (c-fms) and cyclooxygenase-2 (COX-2) in cervical carcinogenesis and to analyze the correlation of VEGF with c-fms and COX-2 expression. METHODS: In this study, 26 cases of benign cervix, 28 low-grade cervical intraepithelial neoplasia (CIN; CIN 1), 30 high-grade CIN (CIN 2/3) and 28 squamous cervical carcinomas (SCC) were examined by immunohistochemistry (IHC) and analysis was performed separately for epithelium and stroma. RESULTS: Positive epithelial expressions in normal cervix, low-grade CIN, high-grade CIN and SCC were, respectively: VEGF - 11.5%, 39.3%, 53.3% and 75% (P<0.001); c-fms - 0%, 10.7%, 40% and 67.9% (P<0.001); COX-2 - 7.7%, 39.3%, 80% and 100% (P<0.001). Stromal VEGF expression was higher than epithelial expression in all CIN grades and was also associated with the lesion grade, while c-fms and COX-2 stromal expression was weak. VEGF expression was statistically correlated to c-fms and COX-2 expression in high-grade CIN (P=0.020 and P=0.027, respectively) and SCC (P=0.015 and P=0.005, respectively). CONCLUSIONS: On the basis of our findings, these factors may participate in the development and progression of CIN lesions, with possible interaction of c-fms and COX-2 on VEGF expression, and may be potential molecular targets for studies of cervical cancer prevention and treatment.

Morphine does no promote esophageal carcinogenesis in rats exposed to diethylnitrosamine.

BACKGROUND: The high incidence of esophageal cancer in the north of Iran has been associated to the consumption of opium and exposure to nitrosamines. Diethylnitrosamine has an established potential of producing experimental cancer in the esophagus and liver. AIM: To evaluate by histopathology the effect of oral administration of morphine and diethylnitrosamine during 23 weeks on the hepatic and esophageal carcinogenesis on 176 rats. METHODS: We divided the rats into the following groups: Morph: morphine; Den: diethylnitrosamine; Den+morph: Den and morphine in the same solution; Den/morph: Den and morphine in different solutions and days. RESULTS: Morphine did not promote neoplasias. The highest neoplastic incidents were found: a) in the esophagus, Den in relation to Den/morph and Den+morph (71.1%, 55.8%, and 50.0%); b) in the liver, Den and Den/morph in relation to Den+morph (73.8%, 81.4%, and 40.9%); c) higher incident of hepatic neoplasia than esophageal in Den/morph (81.4% and 55.8%). Different doses of diethylnitrosamine were ingested among the groups Den, Den/morph, and Den+morph, respectively 2.9, 2.8, and 2.3 mg/kg/day. CONCLUSIONS: These results show that the morphine did not promote esophageal carcinogenesis and may have stimulated the hepatic metabolism of the first pass of the carcinogen.

Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial.

OBJECTIVE: To evaluate the equivalence of ceftriaxone plus doxycycline or azithromycin for cases of mild pelvic inflammatory disease (PID). METHODS: Patients with PID received an intramuscular injection of 250 mg of ceftriaxone, and were randomly assigned to receive 200 mg/d of doxycycline for 2 weeks, or 1 g of azithromycin per week, for 2 weeks. The degree of pain was assessed on days 2, 7, and 14 and clinical cure was assessed on day 14. RESULTS: From 133 patients eligible for the study, 13 were excluded for having conditions other than PID, 11 were lost on follow-up, and three had oral intolerance to the antibiotics, yielding 106 for protocol analysis. No significant difference was observed regarding the degree of pain between the doxycycline and azithromycin groups. Clinical cure per protocol was 98.2% (56 of 57; 95% confidence interval [CI], 0.9-0.99) with azithromycin, and 85.7% (42 of 49; 95% CI, 0.72-0.93) with doxycycline (P=0.02). In a modified intention to treat analysis, clinical cure was 90.3% (56 of 62; 95% CI, 0.80-0.96) with azithromycin, and 72.4% (42 of 58; 95% CI, 0.58-0.82) with doxycycline (P=.01); a relative risk of 0.35, and a number needed to treat of six for benefit with azithromycin. CONCLUSION: When combined with ceftriaxone, 1g of azithromycin weekly for 2 weeks is equivalent to ceftriaxone plus a 14-day course of doxycycline for treating mild PID.

Computer-assisted immunohistochemical analysis of cervical cancer biomarkers using low-cost and simple software.

The study of biomarkers by immunohistochemistry (IHC) for cervical cancer and intraepithelial lesions is a promising field. However, manual interpretation of IHC and reproducibility of the scoring systems can be highly subjective. In this article, we present a novel and simple computer-assisted IHC interpretation method based on cyan-magenta-yellow-black (CMYK) color format, for tissues with diaminobenzidine cytoplasmatic staining counterstained with methyl green. This novel method is more easily interpreted than previous computer-assisted methods based on red-green-blue (RGB) color format and presents a strong correlation with the manual H-score. It is simple, objective, and requires only low-cost software and minimal computer skills. Briefly, a total of 67 microscopic images of cervical carcinoma, normal cervix, and negative controls were analyzed in Corel Photo Paint X3 software in CMYK and RGB color format, and compared with manual H-score IHC assessments. The clearest and best positive correlation with the H-score was obtained using the image in CMYK color format and crude values of magenta color (Spearman correlation coefficient=0.84; agreement of 93.33%, P<0.001). To obtain this value, only 3 steps were necessary: convert the image to CMYK format, select the area of interest for analysis, and open the color histogram tool to visualize the magenta value.