Human pancreatic precursor cells secrete FGF2 to stimulate clustering into hormone-expressing islet-like cell aggregates

Development of the endocrine pancreas includes a series of early events wherein precursor cells cluster, that is migrate to form cell aggregates, which subsequently differentiate into islets of Langerhans. We show that PANC-1 cells, a human pancreatic cell line, differentiates into hormone-producing islet-like cell aggregates after exposure to a defined serum-free medium. These cells were used to provide the following evidence that fibroblast growth factor (FGF)2 is a paracrine chemoattractant during PANC-1 cell clustering: (i) FGF2 is secreted and remains bound to the extracellular matrix from where it may diffuse to form chemoattractive gradients; (ii) a subset of cells expresses FGF receptors (FGFRs) -1, -2, -3, and -4; (iii) inhibition of FGFR tyrosine kinase inhibits cell clustering; and (iv) FGF2 neutralizing antibody inhibits clustering. In addition, adult human islet-derived precursor cells, which cluster and differentiate in a manner similar to PANC-1 cells, also secrete FGF2 and express FGFRs. We conclude that FGF2, acting as a paracrine chemoattractant, stimulates clustering of precursor cells, an early step leading to islet-like cell aggregate formation. Similar processes may occur during development of the islet of Langerhans in humans.     

Anorectal Physiology and Pathophysiology

The anatomy and physiology of the external anal sphincter, puborectalis muscle, internal anal sphincter, and rectum are described. Measurement techniques are reviewed emphasizing those which can be carried out by the gastroenterologist in independent office practice, and the range of normal values for each test is given. A protocol for diagnostic evaluation of anorectal disorders is recommended which includes testing for rectal prolapse and for descent of the perineum by having the patient strain while seated on a commode chair, evaluating the external and internal anal sphincters by recording EMG with an anal plug, or recording pressures with a perfused catheter or balloon probe, using a rectal balloon to evaluate the maximum tolerable volume of rectal distension and the minimum (threshold) volume of a bolus injection which can be subjectively perceived, and arranging with a radiologist to perform a proctogram--a radiograph of the rectum and anal canal during rest and when the patient strains to defecate--in order to evaluate the anorectal angle (puborectalis muscle) and to detect rectocele and intussusception. These objective tests should be supplemented by a careful clinical history and physical examination.     

Esthesioneuroblastoma: An Update on the UCLA Experience, 2002–2013

Objectives To profile the clinical presentation and treatment results of esthesioneuroblastomas at the University of California, Los Angeles (UCLA), from 2002 to 2013. Design Retrospective review. Setting Tertiary academic institution. Participants Forty-one patients with esthesioneuroblastomas treated at UCLA. Main Outcome Measures Overall survival (OS) and recurrence-free survival (RFS). Results Thirty-six patients were included with a mean age of 50.1 years and a median duration of follow-up of 33 months. The 5-year RFS and OS were 54% and 82%, respectively. Modified Kadish stage was the only factor identified to affect OS. Multivariate analysis demonstrated that tumor grade was the only factor that had an independent impact on RFS. There was no statistical difference in survival among the surgical approaches chosen. Conclusions The updated data on the UCLA experience reveals that all three surgical approaches chosen provide comparable survival, although longer follow-up will be needed to ascertain if these findings hold true. The endoscopic approach had a statistically significant decrease in length of hospital stay and a trend toward reduced blood loss, intensive care unit admission, and complications. The modified Kadish staging was the only factor identified to predict OS. Multivariate analysis revealed that tumor grade was an independent predictor of recurrence; therefore, its importance should be emphasized in future staging systems.     

Benign cecal ulcers

Benign ulceration of the cecum is an uncommon lesion. Most cases are diagnosed intraoperatively and most authors have advocated right hemicolectomy due to the difficulty in differentiating benign from malignant lesions. Recently colonoscopic diagnosis and conservative treatment have been reported. We describe six cases of cecal ulcer ranging from asymptomatic lesions diagnosed at colonoscopy and healing with conservative management to perforated ulcers with intra-abdominal abscesses requiring right hemicolectomy. A selective approach to patient management is advocated, including stapler wedge cecectomy with frozen section diagnosis to avoid extensive bowel resection and retain the ileocecal valve.