Correlation between Breast Self-Examination Practices and Demographic Characteristics, Risk Factors and Clinical Stage of Breast Cancer among Iraqi Patients.

BACKGROUND: Breast Cancer (BC) is the most common cancer and the leading cause of cancer death among women globally. The disease can be cured with limited resources if detected early. Breast self-examination (BSE) is considered a cost-effective feasible approach for early detection of that cancer in developing countries. AIM: To determine the correlation between BSE performance and demographic characteristics, risk factors and clinical stage of BC among Iraqi patients. METHODS: This retrospective study included a total of 409 female patients diagnosed with BC at the Referral Training Center for Early Detection of Breast Cancer and the National Cancer Research Center in Baghdad. The studied variables included the age of the patient, occupation, marital and educational status, parity, history of lactation, contraceptive pill intake, family history of cancer and the clinical stage of the disease. RESULTS: Our findings revealed that the most important predictors for practicing BSE was family history of BC or any other cancers (OR = 3.87, P = 0.018) followed by being a governmental employee (OR = 1.87, P = 0.024), history of contraceptive use (OR = 1.80, P = 0.011) and the high level of education (OR = 1.73, P = 0.004). On the other hand, there was no significant correlation between the practice of BSE and the BC stage at the time of presentation. CONCLUSION: There is a relatively poor practice of BSE among Iraqi patients diagnosed with BC. It is mandatory to foster the national cancer control strategies that focus on raising the level of awareness among the community through public education as a major approach to the early detection of cancer in Iraq.

Tube Feed Necrosis after Major Gastrointestinal Oncologic Surgery: Institutional Lessons and a Review of the Literature.

BACKGROUND: Small bowel necrosis after enteral feeding through a jejunostomy tube (tube feed necrosis, TFN) is a rare, serious complication of major abdominal surgery. However, strategies to reduce the incidence and morbidity of TFN are not well established. Here, in the largest series of TFN presented to date, we report our institutional experience and a comprehensive review of the literature. METHODS: Eight patients who experienced TFN from 2000 to 2014 after major abdominal surgery for oncologic indications at the University of Cincinnati were reviewed. Characteristics of post-operative courses and outcomes were reviewed prior to and after a change in tube-feeding protocol. The existing literature addressing TFN over the last three decades was also reviewed. RESULTS: Patients with TFN ranged from 50 to 74 years old and presented with upper gastrointestinal tract malignancies amenable to surgical resection. Six and two cases of TFN occurred following pancreatectomy and esophagectomy, respectively. Prior to TF protocol changes, which included initiation at a low rate, titrating up more slowly and starting at one-half strength TF, three of six cases of TFN (50%) resulted in mortality. With the new TF protocol, there were no deaths, goal TF rate was achieved 3 days later, symptoms of TFN were recognized 3 days earlier, and re-operation was conducted 1 day earlier. CONCLUSION: This case series describes a change in clinical practice that is associated with decreased morbidity and mortality of TFN. Wider implementation and further refinement of this tube-feeding protocol may reduce TFN incidence at other institutions and in patients with other conditions requiring enteral nutrition.

Measurement of natural radioactivity and dose rate assessment of terrestrial gamma radiation in the soil of southern Punjab, Pakistan.

Activity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs in soil samples collected from the most populous area of southern Punjab of Pakistan have been measured by gamma-ray spectrometry. The measured activity concentrations for these radionuclides are compared with the reported data from different other countries and it is found that measured activity concentrations are comparable with the worldwide measured average values reported by the UNSCEAR. Subsequently assessed radiological effects show that the mean radium equivalent activity (Ra(eq)) is 96.7 +/- 15.2 Bq kg(-1) and air absorbed dose rate (D) is 46.1 +/- 7.3 nGy h(-1). The values of internal and external radiation hazard indices are found to be less than unity. The annual effective radiation dose is calculated to be 0.28 +/- 0.05 mSv, which is well below the limit of 1.0 mSv y(-1) recommended by the International Commission on Radiological Protection, for the general public.

Primary osteosarcoma of the skull.

Primary osteogenic sarcoma of the skull is an exceedingly rare condition. An adult male patient is described, who had a painless swelling in the right forehead that had rapidly enlarged in the previous 6 months. Radiological investigations showed a large destructive mass lesion involving the right side of the frontal bone with extension into the frontal sinus, causing marked extradural compression of brain parenchyma. Histopathological examination confirmed the lesion to be primary osteogenic sarcoma.

The significance and clinical factors associated with a subcentimeter resection of colorectal liver metastases.

BACKGROUND: Prognosis after resection of colorectal liver metastases is influenced by various factors. A positive margin of resection (MOR) has been shown to adversely influence prognosis. Although a 1-cm MOR has been accepted as adequate, the data to support this guideline are sparse. METHODS: Our hepatobiliary database was queried for patients who underwent liver resection for colorectal metastases between January 1992 and July 2003. All patients were divided into three groups: MOR <.5 cm (group A), .5 to 1 cm (group B), and >1 cm (group C). Operative reports from each hepatic resection were analyzed to determine local factors that may have contributed to a subcentimeter MOR. RESULTS: A total of 112 patients (67 men and 45 women) underwent liver resection for colorectal metastases with negative margins. Fifty-three patients were in group A, 26 patients were in group B, and 33 patients were in group C. Group C demonstrated decreased local recurrence (LR; P = .003), distant recurrence (DR; P = .008), and disease-free recurrence (P = .002). A significant difference in the overall time to LR (P = .003), time to DR (P = .003), and disease-free survival (P = .002) was also demonstrated. Factors associated with a subcentimeter MOR included nonanatomical resection (P = .043), proximity to a major vessel (P = .003), and central location (P = .002). CONCLUSIONS: A <1-cm resection for colorectal liver metastases is associated with increased LR and DR, as well as decreased disease-free survival. When a nonanatomical resection is performed, a MOR >1 cm should be attempted, because an adequate margin is often underestimated. Considerations should be made for extended resections when tumors are centrally located or near major vessels.

Effects of overexpression of ephrin-B2 on tumour growth in human colorectal cancer.

Eph receptor tyrosine kinases (RTKs) and their membrane-bound ligands, the ephrins, are essential for embryonic vascular development. Recently, it has been demonstrated that overexpression of specific Ephs and ephrins is associated with a poor prognosis in human tumours. Our group has shown that EphB and the ephrin-B subfamilies are coexpressed in human colorectal cancer, and ephrin-B2 is expressed at higher levels in human colorectal cancer than in adjacent normal mucosa. As the Eph/ephrin system is involved in embryologic vasculogenesis and ephrin-B2 is expressed ubiquitously in all colon cancers studied in our laboratory, we hypothesised that overexpression of ephrin-B2 in colon cancer cells may induce tumour angiogenesis and increase tumour growth. To investigate this hypothesis, we stably transfected KM12L4 human colon cancer cells with ephrin-B2 to study its effect on tumour growth in vivo. We found that overexpression of ephrin-B2 markedly decreased tumour growth in a mouse xenograft model. Immunohistochemical staining showed that ephrin-B2 transfectants produced higher tumour microvessel density and lower tumour cell proliferation than did parental or vector-transfected control cells. Using (51)Cr-labelled red blood cells (RBCs) to determine the functional blood volume in tumours, we demonstrated that tumours from ephrin-B2-transfected cells had significantly decreased blood volume compared with tumours from parental or vector-transfected control cells. Evaluation of in vitro parameters of cell cycle mediators demonstrated no alteration in the cell cycle. Although ephrin-B2 transfection increased tumour vessel density, the decrease in blood perfusion suggests that these vessels may be 'dysfunctional'. We conclude that overexpression of ephrin-B2 suppresses tumour cell growth and vascular function in this in vivo colon cancer model.

Angiopoietin-1 inhibits tumour growth and ascites formation in a murine model of peritoneal carcinomatosis.

Angiopoietin-1 is an important regulator of endothelial cell survival. Angiopoietin-1 also reduces vascular permeability mediated by vascular endothelial growth factor. The effects of angiopoietin-1 on tumour growth and angiogenesis are controversial. We hypothesised that angiopoietin-1 would decrease tumour growth and ascites formation in peritoneal carcinomatosis. Human colon cancer cells (KM12L4) were transfected with vector (pcDNA) alone (control) or vector containing angiopoietin-1 and injected into the peritoneal cavities of mice. After 30 days, the following parameters were measured: number of peritoneal nodules, ascites volume, and diameter of the largest tumour. Effects of angiopoietin-1 on vascular permeability were investigated using an intradermal Miles assay with conditioned media from transfected cells. Seven of the nine mice in the pcDNA group developed ascites (1.3+/-0.5 ml (mean+/-s.e.m.)), whereas no ascites was detectable in the angiopoietin-1 group (0 out of 10) (P<0.01). Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours. Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05). Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer.

Child clinical/pediatric neuropsychology: some recent advances.

The neuropsychological assets and deficits of several types of pediatric neurological disease, disorder, and dysfunction are described. These are examined from the perspective of the syndrome of nonverbal learning disabilities (NLD) and the "white matter model" designed to explain its complex manifestations. It is concluded that children with some of these diseases exhibit the NLD phenotype, whereas others do not. For the most part, the diseases in which the NLD phenotype is particularly evident are those wherein it has been demonstrated that perturbations of white matter (long myelinated fibers) are particularly prominent.

Overview of angiogenesis: Biologic implications for antiangiogenic therapy.

Tumor angiogenesis is essential for the growth of primary and metastatic tumors. This process requires the coordinated activities of multiple factors and cell types. For tumors to develop a neovascular blood supply, tumor cells and host cells must secrete proangiogenic factors that offset the activities of inhibitory angiogenic factors. In addition, the newly derived tumor endothelium must respond to signals in the microenvironment to survive under conditions such as hypoxia and acidity. Moreover, because the process of angiogenesis is regulated by redundant factors and pathways, inhibition of any single pathway is likely to select for cells whose angiogenesis is driven by other factors. Because antiangiogenic therapy is unlikely to induce tumor regression, the criteria for efficacy must be evaluated by means other than the standard criteria used to evaluate cytotoxic chemotherapy. Understanding the basic principles that drive tumor angiogenesis will lead to the development of therapies that will likely prolong survival without the toxicity associated with standard chemotherapy.

Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma. A possible mechanism for the initiation of angiogenesis.

BACKGROUND: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are important regulators of endothelial cell (EC) survival. Current models suggest that an increase in Ang-2 expression in ECs leads to the initiation of angiogenesis. The authors hypothesized that the imbalance of Ang-1 and Ang-2 activities in colon carcinoma leads to a net gain in Ang-2 function. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses and immunofluorescent double-staining were performed to examine human colon carcinoma cell lines, surgical specimens, normal mucosa, and liver metastases for the expression of Ang-1 and Ang-2. RESULTS: RT-PCR analyses revealed that 7 of 18 colon carcinoma cell lines expressed Ang-1, and 14 of 18 colon carcinoma cell lines expressed Ang-2 (P < 0.05). Of the surgical specimens from patients with colon carcinoma, 6 of 11 specimens expressed Ang-1, and 11 of 11 specimens expressed Ang-2 (P < 0.05). However, Ang-1 and Ang-2 were expressed with relative equal frequency in normal mucosa (P = 0.62). Immunofluorescent staining (n = 20 specimens) revealed the presence of Ang-2 protein in normal mucosa and tumor epithelium, but Ang-1 was expressed only in normal mucosa. A similar pattern was found for hepatic colorectal metastases. Double staining for Ang-1 or Ang-2 and cytokeratin-22 (an epithelial marker) demonstrated that Ang-1 was produced by uninvolved, normal colonic epithelium, whereas Ang-2 was produced by normal and malignant colonic epithelium. CONCLUSIONS: In patients with colon carcinoma, Ang-2 is expressed ubiquitously in tumor epithelium, whereas expression of Ang-1 in tumor epithelium is rare. The net gain of Ang-2 activity is possibly an initiating factor for tumor angiogenesis.

Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors.

Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and induce apoptosis in colon cancer in in vivo and in vitro systems. We hypothesized that simultaneous blockade of the VEGF and EGF receptors would enhance the therapy of colon cancer in a mouse model of peritoneal carcinomatosis. Nude mice were given intraperitoneal injection of KM12L4 human colon cancer cells to generate peritoneal metastases. Mice were then randomized into one of four treatment groups: control, anti-VEGFR (DC101), anti-EGFR (C225), or DC101 and C225. Relative to the control group, treatment with DC101 or with DC101+C225 decreased tumour vascularity, growth, proliferation, formation of ascites and increased apoptosis of both tumour cells and endothelial cells. Although C225 therapy did not change any of the above parameters, C225 combined with DC101 led to a significant decrease in tumour vascularity and increases in tumour cell and endothelial cell apoptosis (vs the DC101 group). These findings suggest that DC101 inhibits angiogenesis, endothelial cell survival, and VEGF-mediated ascites formation in a murine model of colon cancer carcinomatosis. The addition of C225 to DC101 appears to lead to a further decrease in angiogenesis and ascites formation. Combination anti-VEGF and anti-EGFR therapy may represent a novel therapeutic strategy for the management of colon peritoneal carcinomatosis.

The effects of angiopoietin-1 and -2 on tumor growth and angiogenesis in human colon cancer.

Angiopoietin (Ang) 1 and Ang-2 are important regulators of endothelial cell survival. Current models suggest that an increase in Ang-2 expression in endothelial cells leads to initiation of angiogenesis. We stably transfected HT29 colon cancer cells with cDNA constructs for Ang-1 or -2 or with vector alone, injected the cells s.c. into nude mice, and assessed tumor growth. Immunohistochemical analyses confirmed sustained increases of Ang-1 and -2 in the tumors. The tumors produced by the Ang-2-transfected cells were larger than the tumors produced in the other groups; those tumors also had higher vessel counts and proliferative indices than tumors in the other groups. Tumors produced by the Ang-1 transfectants had fewer vessels and lower tumor cell proliferative indices than tumors in the other groups. These data suggest that imbalances between Ang-1 and -2 that result in a net gain of Ang-2 activity lead to enhanced tumor angiogenesis and growth.

Effects of an antibody to vascular endothelial growth factor receptor-2 on survival, tumor vascularity, and apoptosis in a murine model of colon carcinomatosis.

Vascular endothelial growth factor (VEGF) is the predominant regulator of colon cancer angiogenesis and is associated with a poor prognosis and the development of metastases. We hypothesized that DC101, an antibody against the VEGF receptor-2 (flk-1), may be efficacious in the therapy of colon cancer peritoneal carcinomatosis in a murine model. BALB/c mice underwent intraperitoneal injection of CT-26 colon cancer cells to generate peritoneal metastases. Mice received control solvent or DC101 for up to 60 days. In parallel studies, mice were sacrificed at sequential time points to determine the effect of DC101 on tumor angiogenesis, tumor cell proliferation and apoptosis, and endothelial cell apoptosis. Mice treated with DC101 demonstrated a 30% increase in mean survival. In addition, DC101 also led to a significant decrease in tumor vascularity, growth and tumor cell proliferation. In sequential studies, anti-VEGF-R therapy led to a progressive increase in endothelial cell apoptosis followed by an increase in tumor cell apoptosis. These findings suggest that anti-flk-1 therapy may prolong survival in patients with colon cancer carcinomatosis. The temporal studies demonstrating that anti-flk-1 therapy lead to an increase in endothelial cell apoptosis that in turn lead to an increase in tumor cell apoptosis confirms the role of VEGF as an endothelial cell survival factor.

Endothelial survival factors as targets for antineoplastic therapy.

Angiogenesis is essential for the growth and metastasis of solid tumors. The angiogenic process includes not only development of new blood vessels but also maintenance of the existing vasculature. Recent studies have demonstrated that several factors induce angiogenesis and also function as endothelial cell survival factors. Vascular endothelial growth factor, a potent angiogenic factor, is an endothelial cell survival factor whose tyrosine kinase receptors are limited to endothelial cells. Members of the angiopoietin family also bind to an endothelial cell-specific tyrosine kinase receptor. Angiopoietin-1 has been shown to stabilize endothelial cell networks, whereas angiopoietin-2 is antagonistic to angiopoietin-1 and destabilizes endothelial cell networks. Pericytes contribute to endothelial cell stabilization by cell-cell contact, secretion of survival factors, or both. In addition, integrins may function as endothelial cell survival factors by numerous mechanisms after binding to the extracellular matrix. The effects of many endothelial cell survival factors act in concert with vascular endothelial growth factor to enhance this essential step in angiogenesis. Targeting any of the aforementioned mechanisms for endothelial cell survival may provide novel therapeutic antineoplastic strategies.

Vascular endothelial growth factor is upregulated by interleukin-1 beta in human vascular smooth muscle cells via the P38 mitogen-activated protein kinase pathway.

Small tumor vessels are composed of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). These cells have been shown to communicate with each other via cytokine signaling during neovascularization. We previously demonstrated that interleukin-1 beta (IL-1 beta) leads to induction of vascular endothelial growth factor (VEGF) in human colon carcinoma cells. As pericytes play a role in regulating EC function, we hypothesized that IL-1 beta may mediate EC survival by induction of VEGF in a paracrine manner. We investigated the effects of IL-1 beta on VEGF expression in human VSMCs (hVSMCs) and the signal transduction pathways that may be involved. Treatment of hVSMCs with IL-1 beta induced VEGF expression in a time- and concentration-dependent manner and increased both the VEGF promoter activity and the mRNA half-life. Treatment with IL-1 beta induced the expression of P38 mitogen-activated protein kinase (MAPK) within 5 min but did not activate extracellular signal-regulated kinases (Erk)-1/2, c-jun amino terminal kinase (JNK), or Akt. SB203580, a specific P38 MAPK inhibitor, blocked the ability of IL-1 beta to induce VEGF mRNA and promoter activity. Conditioned media from hVSMCs pretreated with IL-1 beta prevented apoptosis of ECs, an effect that was partially abrogated by VEGF-neutralizing antibodies. These data demonstrate that IL-1 beta may induce VEGF in hVSMCs, and suggest that this paracrine signaling pathway, may prevent, in part, apoptosis of ECs.

Hepatitis B or C virus serology as a prognostic factor in patients with hepatocellular carcinoma.

It is not clear whether chronic hepatitis B or C virus (HBV or HCV) infection is a prognostic factor for hepatocellular carcinoma. We performed this study to determine if chronic HBV or HCV infection had any impact on postresection survival or affected patterns of failure. The records of 77 patients undergoing surgical resection for hepatocellular carcinoma between January 1990 and December 1998 were reviewed. Forty-four patients (57%) had HCV infection, 18 patients (23%) had HBV infection, and 15 patients (20%) had negative serology. There were no differences in age, sex, or tumor size among the groups, and all patients had margin-negative resections. There was a significantly higher incidence of satellitosis and vascular invasion in patients with HCV infection (32% and 41% respectively; P <0.05 vs. other groups). With a median follow-up of 30 months, a significantly decreased local disease-free survival (LDFS) was seen in HBV-positive (5-year LDFS 26%) or HCV-positive (5-year LDFS 38%) patients compared to those with negative serology (5-year LDFS 79%; P <0.05). There was also a trend toward a decreased overall survival in patients with positive hepatitis serology compared to patients with negative serology (37% vs. 79%; P = 0.12). Univariate analysis revealed that only satellitosis was related to local recurrence and overall survival. Patients with positive serology for hepatitis B or C undergoing resection for hepatocellular carcinoma have a trend toward worse overall prognosis and a significantly decreased LDFS when compared to patients with negative serology.

Management of intravaginal warts in women with 5-fluorouracil (1%) in vaginal hydrophilic gel: a placebo-controlled double-blind study.

The purpose of this placebo-controlled, double-blind study was to determine the safety, tolerability and clinical efficacy of 5-fluorouracil (1%) in a vaginal hydrophilic gel (hydroxyethylcellulose, 1%) to cure intravaginal papillomas in women. Pre-selected, 60 women ranging between 18 and 50 years of age (mean 24.6), having 312 vaginal condylomas (mean 5.2) joined the study. The diagnosis of human papillomavirus (HPV) was established with clinical, histopathological and polymerase chain reaction (PCR) techniques. Subjects were randomized into 2 parallel groups. Each patient was allocated a pre-coded tube 15 g (active or placebo) with graduated vaginal applicators (disposable), and instructions how to insert 4 g of the trial medication deep into the vagina once at bedtime on every other day (1, 3 and 5) per week, to visit the clinic on day 7 for clinical evaluations and to receive the same pre-coded replacement to continue the regimen for another week. A maximum 12 applications were to be used in 4 weeks. Cure was defined as absence of clinical signs of infection, re-confirmed by PCR and Southern blot hybridization negative HPV DNA. By the end of the treatment 48.4% patients and 51.9% lesions were cured. Breaking the code revealed that 5-fluorouracil (1%) gel had cured 83.3% patients and 87% intravaginal warts. Placebo resolved 13.3% patients and 14% condylomas; (active gel versus placebo; P < 0.001). Twelve patients (20%) mostly in the active gel experienced mild erythema, erosion and oedema, with no drop-outs. Among cured patients 3 had a relapse after 16 months. In conclusion, the clinical results of the study demonstrate that 5-fluorouracil (1%) in a vaginal hydrophilic gel is safe, tolerable and significantly more effective than placebo to cure intravaginal warts in women.

Occupational exposure and respiratory illness symptoms among textile industry workers in a developing country.

This study investigates the respiratory health profile of textile mill workers in Bangladesh, aiming to develop workers' awareness and public attention, and to ensure a proper implementation of health and safety measures. Forced vital capacity was measured by peak expiratory flow rate instrument among 210 subjects. The personal history, the occupational history, and the state of health were also determined using a questionnaire and checklists. The subjects who had a considerably low peak expiratory flow rate (< 290 liters/min), and had symptoms of chronic respiratory illness, underwent X-ray examination. A statistically significant low peak expiratory flow rate was identified among 52.9 percent of workers. Among them, 42.9 percent had symptoms of cough with or without phlegm; 5.7 percent had a history of chronic bronchitis and/or asthma, and 4.3 percent experienced chest tightness or breathlessness. This study showed a high degree (p < .001) of respiratory-related illness symptoms present among the workers in the blow/card rooms and the workers in the spinning section. Irrespective of variation of age as well as work pattern, non-smokers were less likely to be affected. Whether worker were occupationally exposed to other incidences was also investigated. The results of these investigations are presented and the findings discussed in light of other studies carried among similar occupational groups.