Phenotype, cancer risk, and surveillance in Beckwith-Wiedemann syndrome depending on molecular genetic subgroups.

Patients with Beckwith-Wiedemann syndrome (BWS) have an increased risk to develop cancer in childhood, especially Wilms tumor and hepatoblastoma. The risk varies depending on the cause of BWS. We obtained clinical and molecular data in our cohort of children with BWS, including tumor occurrences, and correlated phenotype and genotype. We obtained similar data from larger cohorts reported in the literature. Phenotype, genotype and tumor occurrence were available in 229 of our own patients. Minor differences in phenotype existed depending on genotype/epigenotype, similar to earlier studies. By adding patients from the literature, we obtained data on genotype and tumor occurrence of in total 1,971 BWS patients. Tumor risks were highest in the IC1 (H19/IGF2:IG-DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS-DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and the group in whom no molecular defect was detectable (6.7%). Wilms tumors (median age 24 months) were frequent in the IC1 (24%) and pUPD (7.9%) subgroups. Hepatoblastoma occurred mostly in the pUPD (3.5%) and IC2 (0.7%) subgroups, never in the IC1 and CDKN1C subgroups, and always before 30 months of age. In the CDKN1C subgroup 2.8% of patients developed neuroblastoma. We conclude tumor risks in BWS differ markedly depending on molecular background. We propose a differentiated surveillance protocol, based on tumor risks in the various molecular subgroups causing BWS. © 2016 Wiley Periodicals, Inc.

Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood.

The Beckwith-Wiedemann syndrome is caused by disturbed imprinting of genes at 11p15.5. Routine diagnostic testing for Beckwith-Wiedemann syndrome (BWS) includes methylation analysis of the imprinting centers ICR1 and ICR2 in DNA extracted from lymphocytes. In approximately 15% of BWS patients the diagnosis cannot be molecularly confirmed. In this study we determined the methylation status in resected tongue tissue of 11 BWS patients and compared this to the genetic defects found by routine diagnostic screening of blood lymphocytes. In all three patients with normal methylation levels in blood, aberrant methylation patterns were found in tongue tissue. In two patients a UPD was detected and the third case had hypermethylation of ICR1. This result shows that tissue specific mosaic (epi)genetic changes, not present in blood, is the underlying defect in at least a subset of BWS patients without a molecular diagnosis after standard genetic testing.

Perioperative antibiotics in the setting of microvascular free tissue transfer: current practices.

Microvascular free tissue transfer is a ubiquitous and routine method of restoring anatomic defects. There is a paucity of data regarding the role of perioperative antibiotics in free tissue transfer. We designed a survey to explore usage patterns among microvascular surgeons and thereby define a standard of care. A 24-question survey regarding the perioperative antibiotic use in microvascular head and neck, breast, and lower extremity reconstruction was sent to all those members of the American Society for Reconstructive Microsurgery who had registered e-mail addresses ( N = 450). Ninety-nine members responded. A first-generation cephalosporin is the most frequent choice of perioperative antibiotics across most categories: 93.5% for breast, 59.2% for head and neck, 91.1% for nontraumatic lower extremity, and 84.9% for traumatic noninfected lower extremity reconstruction. In penicillin-allergic patients, clindamycin is the most common choice. For traumatic lower extremity reconstruction in the presence of soft tissue infection or osteomyelitis, culture and sensitivity results determine the selection of perioperative antibiotics in 74%. A first-generation cephalosporin is the standard of care for perioperative antibiotic use in microvascular breast, head and neck, nontraumatic lower extremity, and traumatic noninfected lower extremity reconstruction. No consensus exists regarding the appropriate duration of coverage. These data may serve as a guide until a large controlled prospective trial is performed and a standard of care is established.

A rapidly resorbable hemostatic biomaterial based on dihydroxyacetone.

We have developed a rapid acting, rapidly resorbable, non-toxic, topical hemostatic agent comprised of a PEGylated, polymerized sequence of dihydroxyacetone (MPEG-pDHA) that is highly effective in vivo. Twenty-eight Sprague-Dawley rats underwent left lateral hepatectomy. To the cut edge of the liver, rats received MPEG-pDHA (50 mg), normal saline (0.5 mL), or Instat (50 mg), a commercially available hemostatic compound. Bleeding time and total blood loss were quantified. Coagulation studies and scanning electron microscopy were performed on phlebotomized blood combined with MPEG-pDHA. Rats treated with MPEG-pDHA had significantly decreased bleeding time (97 s) and total blood loss (1.35 g) compared to normal saline (464 s and 3.83 g, p < 0.05 for each), and a significantly shorter bleeding time compared to Instat (165 s, p < 0.05). Histology confirmed that all MPEG-pDHA was metabolized within 3 weeks. The addition of MPEG-pDHA to whole blood did not significantly affect prothrombin time (12.0 s vs. 13.2 s, p = 0.130), partial thromboplastin time (27.0 s vs. 21.8 s, p = 0.118), or thrombin clotting time. MPEG-pDHA is an effective and rapidly resorbable hemostatic agent that may find broad hemostatic application in a wide range of surgical procedures.