Donald McCrann

Nonbilharzial bladder carcinoma complicating pregnancy: review of the literature.

The purpose of this review is to evaluate tumor presentation and characteristics, and maternal-fetal outcomes of pregnancies complicated by nonbilharzial bladder carcinoma. The mean age of the patients was 29.5 years (range = 18–40). Symptoms and diagnosis occurred after the first trimester in 20 (83%) and 22 (92%) cases, respectively. Presenting complaints included painless gross hematuria [N = 12 (50%)], vaginal bleeding [N = 7 (29%)], dysuria [N = 2 (8.4%)], abdominal pain [N = 2 (8.4%)], and 1 instance each of urgency, frequency, recurrent cystitis, and no symptoms. Tumors were initially identified by ultrasound [N = 12 (50%)], cystoscopy [N = 11 (46%)], and intravenous urography [N = 1 (4.5%)]. Transitional cell carcinoma was found in 17 (74%), adenocarcinoma in 5 (22%), and squamous cell carcinoma in 1 (4.5%) patient. Tumors did not favor a specific bladder location, tended to be low grade [8 (40%) = grade 1, 7 (35%) = grade 2; 5 (21%) = grade 3], and noninvasive [N = 19 (79%)]. Treatment was typically by transurethral resection (N = 18), but 3 women required radical cystectomy, 2 received radiation, 1 received chemotherapy, and 1 underwent partial cystectomy. Three (14%) women died of their disease and 3 (14%) fetuses were lost because of complications of cancer or its treatment. Bladder carcinoma in pregnancy can mimic cystitis or obstetric hemorrhage and should be considered when evaluations for these conditions are negative. Routine ultrasound evaluation of the bladder in these patients may improve the diagnostic yield. Pregnancy is not a contraindication to treating most forms of bladder cancer. Target Audience: Obstetricians and Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to list the various types of bladder cancers, to describe the presenting symptoms in a patient with a bladder cancer, and to outline the work up and treatment strategies for bladder cancer.

Prenatal diagnosis of congenital anomalies requiring surgical correction. Implications for the future.

With the use of maternal ultrasonography, 22 infants had an anomaly identified before delivery. Nine had gastrochisis. In all, ultrasonography was performed because of an elevated maternal serum alpha 1 fetoprotein level. Ultrasonography for other indications identified three infants with omphaloceles, three with cystic adenomatoid malformation of the lung, two with duodenal atresia, two with posterior urethral valves, and one each with obstruction of the ureteropelvic junction, a retroperitoneal teratoma, and an ovarian cyst. Infants were delivered in a neonatal center able to provide total care from the time of birth, thus the risks of transport over long distances were avoided. One of the infants with cystic adenomatoid malformation was incorrectly diagnosed as having a congenital diaphragmatic hernia, and the complete posterior urethral valve bilateral hydronephrosis complex was not identified in this infant until after delivery. The ability to diagnose complex anomalies correctly places new responsibilities on the surgeon who must counsel the parents on his ability to successfully treat the identified anomaly. Improved diagnostic accuracy, increased case findings, careful counselling, and delivery of high-risk infants in regional centers must be major priorities to improve neonatal surgical care in the next decade.

RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development

Ligation of erythropoietin (EPO) receptor (EPOR) JAK2 kinase complexes propagates signals within erythroid progenitor cells (EPCs) that are essential for red blood cell production. To reveal hypothesized novel EPOR/JAK2 targets, a phosphotyrosine (PY) phosphoproteomics approach was applied. Beyond known signal transduction factors, 32 new targets of EPO-modulated tyrosine phosphorylation were defined. Molecular adaptors comprised one major set including growth factor receptor-bound protein 2 (GRB2)–associated binding proteins 1–3 (GAB1-3), insulin receptor substrate 2 (IRS2), docking protein 1 (DOK1), Src homology 2 domain containing transforming protein 1 (SHC1), and sprouty homologue 1 (SPRY1) as validating targets, and SPRY2, SH2 domain containing 2A (SH2D2A), and signal transducing adaptor molecule 2 (STAM2) as novel candidate adaptors together with an ORF factor designated as regulator of human erythroid cell expansion (RHEX). RHEX is well conserved in Homo sapiens and primates but absent from mouse, rat, and lower vertebrate genomes. Among tissues and lineages, RHEX was elevated in EPCs, occurred as a plasma membrane protein, was rapidly PY-phosphorylated >20-fold upon EPO exposure, and coimmunoprecipitated with the EPOR. In UT7epo cells, knockdown of RHEX inhibited EPO-dependent growth. This was associated with extracellular signal-regulated kinase 1,2 (ERK1,2) modulation, and RHEX coupling to GRB2. In primary human EPCs, shRNA knockdown studies confirmed RHEX regulation of erythroid progenitor expansion and further revealed roles in promoting the formation of hemoglobinizing erythroblasts. RHEX therefore comprises a new EPO/EPOR target and regulator of human erythroid cell expansion that additionally acts to support late-stage erythroblast development.