Incidence,Risk Factors,and Obstetrical Outcomes of Women with Breast Cancer in Pregnancy

Abstract: Breast cancer in pregnancy is a rare condition. The objective of our study was to describe the incidence, risk factors, and obstetrical outcomes of breast cancer in pregnancy. We conducted a population‐based cohort study on 8.8 million births using data from the Healthcare Cost and Utilization Project – Nationwide Inpatient Sample from 1999–2008. The incidence of breast cancer was calculated and logistic regression analysis was used to evaluate the independent effects of demographic determinants on the diagnosis of breast cancer and to estimate the adjusted effect of breast cancer on obstetrical outcomes. There were 8,826,137 births in our cohort of which 573 cases of breast cancer were identified for an overall 10‐year incidence of 6.5 cases per 100,000 births with the incidence slightly increasing over the 10‐year period. Breast cancer appeared to be more common among women >35 years of age, odds ratio (OR) = 3.36 (2.84–3.97); women with private insurance plans, OR = 1.39 (1.10–1.76); and women who delivered in an urban teaching hospital, OR = 2.10 (1.44–3.06). After adjusting for baseline characteristics, women with pregnancy‐associated breast cancer were more likely to have an induction of labor, OR = 2.25 (1.88, 2.70), but similar rates of gestational diabetes, preeclampsia, instrumental deliveries, and placental abruption. The incidence of breast cancer in pregnancy appears higher than previously reported with women over 35 being at greatest risk. Aside from an increased risk for induction of labor, women with breast cancer in pregnancy have similar obstetrical outcomes.     

DOES SILDENAFIL COMBINED WITH TESTOSTERONE GEL IMPROVE ERECTILE DYSFUNCTION IN HYPOGONADAL MEN IN WHOM TESTOSTERONE SUPPLEMENT THERAPY ALONE FAILED?

PURPOSE: We evaluated the efficacy of testosterone gel (T-gel) alone and in combination with sildenafil in hypogonadal patients with erectile dysfunction (ED). MATERIALS AND METHODS: A total of 49 hypogonadal men (mean age 60.7 years) with ED participated for a mean of 20.2 months. Blood was tested for total and bioavailable testosterone, and prostate specific antigen. Sexual function was assessed using the International Index of Erectile Function questionnaire and a global assessment question (GAQ). Men received 1% 5 gm T-gel for 6 months, and 100 mg sildenafil was added to those with a "no" response to the GAQ after 3 months on testosterone supplement. RESULTS: A total of 31 patients reported significant improvement in the sexual desire domain (from a mean +/- SD of 4.2 +/- 0.8 to 8.6 +/- 0.4) and erectile function (EF) domain (from 13.6 +/- 1.9 to 27 +/- 0.8) following treatment with testosterone supplement alone. One patient was excluded from study after urinary retention developed and 9 reported irritation at the gel application site. In spite of normalization of total and bioavailable testosterone values, and significant improvement of sexual desire domain scores, the EF of 17 men remained less than 26 or they responded "no" to the GAQ. These men received combined T-gel and sildenafil, after which all graded EF greater than 26 and responded positively to the GAQ. CONCLUSIONS: Combined treatment with sildenafil and T-gel has a beneficial effect on ED in hypogonadal patients in whom treatment with testosterone supplement alone failed.     

Relationship of tumorigenic malignant melanomas to dermal elastin: an expression of tumor/stromal interaction that may be related to prognosis

Malignant melanomas, which produce a large number of substances active in connective tissue modulation, must contend with the dermis to grow and propagate. We studied the morphologic interactions between tumorigenic malignant melanomas and dermal elastin. Formalin-fixed and paraffin-embedded tissues of 108 tumorigenic malignant melanomas were stained for elastic tissue with the Verhoeff-van Gieson method. Various aspects of the relationship between malignant melanoma and dermal elastin were analyzed in relation to the histologic and clinical data using univariate and multivariate analyses. Tumor thickness, mitotic rate, and the presence of elastin remnants within the tumors were found to be independent negative prognostic factors, the latter with borderline significance. Tumors with more remnants of elastin were associated with higher stage of disease and lymph node and distant metastases. Tumor infiltration between the elastic fibers in the tumor depth was associated with high Clark level, greater tumor thickness, high stage of disease, and lymph node metastases. At least partial preservation of elastic fibers in the tumor depth was a relatively good prognostic factor whereas complete absence of elastin was an adverse factor. Focal or multifocal absence of elastin in the midst of the tumors or in their depth was usually associated with lymphocytic infiltrates. We suggest that tumors with remnants of elastic fibers and/or invasion between elastic fibers in their depth may be fast growing and highly invasive. The absence of elastin within tumors and at their advancing edge may be related to the elaboration of elastin-degrading substances by melanoma cells or various inflammatory cells. Our findings indicate that the relationship between malignant melanomas and dermal connective tissue components, specifically elastin, may have prognostic significance.     

MASSIVE GI HEMORRHAGE FROM AN ILEAL DUPLICATION CYST IN AN ADULT

We describe an unusual case of a 32-yr-old man who presented with massive GI hemorrhage as an initial manifestation of an ileal duplication cyst. The lesion was first revealed by visceral angiography during investigation of the bleeding source. At laparotomy, a large ileal duplication containing full-thickness gastric-type mucosa was identified. Ulceration of the ileal mucosa adjacent to the communicating orifice was found to be the source of bleeding. Duplications of the alimentary tract are rare congenital malformations. Patients usually present in infancy and childhood, although delayed complications can present in adulthood. This entity should be considered among other lesions that can cause massive GI hemorrhage not diagnosable by endoscopy.     

Short-term course and outcome of treatments of pleural empyema in pediatric patients: repeated ultrasound-guided needle thoracocentesis vs chest tube drainage

BACKGROUND: Several reports have suggested that early chest tube drainage (CTD) may not be necessary in the treatment of severe pleural empyema (PE) in pediatric patients if appropriate antibiotic therapy and supportive care are provided. OBJECTIVES: A prospective open study to compare the short-term course of two treatment protocols of severe PE in pediatric patients. STUDY DESIGN: One group of 32 patients was treated with early insertion of a chest tube for CTD, and a second group of 35 patients was treated by a repeated ultrasound-guided needle thoracocentesis (RUSGT). The severity of the empyema was assessed by chest radiograph, the amount of fluid drained, the number of days the patient had experienced a fever, and the duration of antibiotic treatment. RESULTS: No significant differences were found between the two groups (RUSGT vs CTD) in all of the following measurements: mean (plus minus SD) duration of a temperature > or = 39 degreesC, 6.2 +/- 2.4 vs 6.5 +/- 1.8 days, respectively; mean duration of a temperature > or = 38 degreesC, 9 +/- 3.9 vs 8.2 +/- 4.5 days, respectively; fluid drained, 35.1 + 23.8 vs 30 +/- 28.2 mL/kg, respectively; duration of antibiotic treatment, 30 +/- 13.2 vs 30.2 +/- 7.3 days, respectively; and length of hospitalization and home IV treatment, 22 +/- 7.6 vs 24.2 +/- 7.5 days, respectively. A failure to respond to treatment occurred in three patients in the RUSGT-treated group and in five patients in the CTD-treated group. The failure to respond occurred in the RUSGT-treated group only in those patients with very large empyemas that caused mediastinal deviation. CONCLUSION: The treatment of PE by RUSGT is as efficacious as CTD, unless PE causes mediastinal deviation.     

Regulation of sperm capacitation and the acrosome reaction by PIP2 and actin modulation

Actin polymerization and development of hyperactivated (HA) motility are two processes that take place during sperm capacitation. Actin polymerization occurs during capacitation and prior to the acrosome reaction, fast F-actin breakdown takes place. The increase in F-actin during capacitation depends upon inactivation of the actin severing protein, gelsolin, by its binding to phosphatydilinositol-4, 5-bisphosphate (PIP₂) and its phosphorylation on tyrosine-438 by Src. Activation of gelsolin following its release from PIP₂ is known to cause F-actin breakdown and inhibition of sperm motility, which can be restored by adding PIP₂ to the cells. Reduction of PIP₂ synthesis inhibits actin polymerization and motility, while increasing PIP₂ synthesis enhances these activities. Furthermore, sperm demonstrating low motility contained low levels of PIP₂ and F-actin. During capacitation there was an increase in PIP₂ and F-actin levels in the sperm head and a decrease in the tail. In spermatozoa with high motility, gelsolin was mainly localized to the sperm head before capacitation, whereas in low motility sperm, most of the gelsolin was localized to the tail before capacitation and translocated to the head during capacitation. We also showed that phosphorylation of gelsolin on tyrosine-438 depends upon its binding to PIP₂. Stimulation of phospholipase C, by Ca²⁺-ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity. In conclusion, these data indicate that the increase of PIP₂ and/or F-actin in the head during capacitation enhances gelsolin translocation to the head. As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility.To acquire the ability to fertilize the egg, mammalian spermatozoa must undergo several biochemical and morphological changes in the female reproductive tract, collectively called capacitation. These changes include cAMP/PKA activation, cholesterol efflux from the plasma membrane, PKA-dependent protein tyrosine phosphorylation, actin polymerization and the development of HA motility.1,2 In a recent study we suggested a mechanism by which the Ser/Thr targeting PKA can lead to Tyr phosphorylation of proteins in the capacitation process. We showed that PKA activates Src which, in turn, inhibits the phosphatase PP1, leading to CaMKII activation, which activates Pyk2 to phosphorylate phosphatidyl-inositol-3-kinase on tyr-458.3We have shown elsewhere that actin polymerization must take place in order to capacitate spermatozoa while very fast depolymerization of F-actin occurs prior to the acrosome reaction.4 It has been suggested that an increase in F-actin during capacitation creates a network in the sperm head between the plasma membrane and the outer acrosomal membrane, and the dispersion of this F-actin must occur to enable acrosomal exocytosis.4,5,6,7 The increase in F-actin in the sperm tail during capacitation is important for the development of HA motility.8 The latter is characterized by an increase in flagellar bending amplitude and an increase in average lateral head movement.9,10 It was shown that the efficiency of HA sperm to penetrate the egg is much higher than non-HA sperm.11 Sperm motility and HA motility are mediated by PLD-dependent actin polymerization.8 It is known that phosphatidylinositol 4,5-bisphosphate (PIP₂) is a cofactor for PLD activation in many cell types.12,13,14,15,16 PIP₂ comprises only 1% of plasma membrane phospholipids, however its extraordinary versatility puts it in the center of plasma membrane dynamics governing cell motility, adhesion, endo- and exocytosis.17,18PIP₂ serves as an effector of several proteins such as Myristoylated alanine-rich C-kinase substrate (MARCKS), gelsolin, PLD and PI3K. These proteins are present in spermatozoa19,20 and are involved in the regulation of sperm capacitation and/or the acrosome reaction. PIP₂ binds gelsolin and release it from actin filaments ends, exposing sites for actin assembly.21 We have shown that the release of bound gelsolin from PIP₂, causes rapid Ca²⁺-dependent F-actin depolymerization as well as an increased acrosome reaction.22 We have also shown that PIP₂ and gelsolin are involved in regulating sperm motility and the development of HA motility.23     

Ultrasonically Guided Fine-Needle Aspiration of Liver Lesions

The aim of the present study was to determine the diagnostic accuracy of ultrasonically guided fine-needle aspiration for liver lesions detected by ultrasound scan. A total of 142 aspirations were carried out in 129 patients with unifocal or multifocal liver lesions suspected of malignancy. The aspiration was made with a 22-gauge needle, guided by ultrasound. Based on histological, cytological, and clinical findings, final diagnoses were reached in 123 patients, 96 of whom had malignant liver disease and 27 benign liver disease. Among the 96 patients with malignant liver disease, the cytological findings revealed malignancy in 78 patients (81.3%) and suspected malignancy in five patients (5.1%), but failed to demonstrate malignancy in 13 patients (13.3%). Among 27 patients with benign liver disease, all the cytological findings indicated benignancy. The overall sensitivity, specificity, and positive and negative predictive values for cytological findings were 86.5%, 100%, 100%, and 76.9%, respectively. The diagnostic accuracy of ultrasonically guided fine-needle aspiration was 89.4%. In one patient with incipient chronic disseminated intravascular coagulation, a fatal intraperitoneal bleeding complicated the procedure. We conclude that ultrasonically guided FNA for cytologic diagnosis of liver lesions is highly accurate and is only rarely associated with fatal complication.     

Is melatonin ready to be used in preterm infants as a neuroprotectant?

The prevention of neurological disabilities following preterm birth remains a major public health challenge and efforts are still needed to test the neuroprotective properties of candidate molecules. Melatonin serves as a neuroprotectant in adult models of cerebral ischemia through its potent antioxidant and anti‐inflammatory effects. An increasing number of preclinical studies have consistently demonstrated that melatonin protects the damaged developing brain by preventing abnormal myelination and an inflammatory glial reaction, a major cause of white matter injury. The main questions asked in this review are whether preclinical data on the neuroprotective properties of melatonin are sufficient to translate this concept into the clinical setting, and whether melatonin can reduce white matter damage in preterm infants. This review provides support for our view that melatonin is now ready to be tested in human preterm neonates, and discusses ongoing and planned clinical trials.