“Per protocol” practice patterns for Children's Oncology Group trials within the radiation oncology community

Little is known about the prevalence of pediatric radiation oncologists treating patients off study according to Children's Oncology Group (COG) trials before data are available regarding toxicity and efficacy of novel radiotherapy regimens. We conducted a 12-question survey of 358 pediatric radiation oncologists to characterize practice patterns regarding ongoing and completed COG protocols off study. With 130 responses (40.3%), the prevalence of providing treatment per protocol, but off study, before data are available in abstract or peer-reviewed form varied from 9.1% (for ACNS1422) to 88.1% (for AHOD1331). Future studies are needed to understand the effects of these practice patterns on outcomes.     

Basaloid squamous carcinoma of the larynx. A potential diagnostic pitfall

Basaloid squamous carcinoma is a rare variant of squamous cell carcinoma. It is frequently diagnosed at an advanced stage with metastases. Histologically, it is identical to basaloid carcinoma at other anatomical sites. Some authors suggest that it may be associated with second primary tumors. Others implicate the Epstein-Barr and human papilloma viruses. All reports but one warn of its aggressive biological behavior. Our case concerns a 52-year-old man who had a small lesion in his right cord. Biopsy of the lesion was performed twice, and conventional squamous cell carcinoma was diagnosed; the patient returned 2 months later with progressed metastatic disease. The patient underwent a laryngectomy and a complete clinical and immunohistochemical investigation. Basaloid squamous carcinoma is a totipotential neoplasm with a grave prognosis. It can be misdiagnosed; therefore, the authors would like to emphasize the significance of this condition in comparison to conventional squamous cell carcinoma, and we provide a review of the relevant recent literature.     

Does percutaneous nephrolithotomy in children cause significant renal scarring?

ObjectiveTo determine the frequency of renal parenchymal damage following percutaneous nephrolithotomy (PCNL) in children.Patients and methodsFifty-six children undergoing PCNL in 60 renal units between January 2000 and December 2004 were included in this prospective study, and were subjected to postoperative technetium-99m dimercaptosuccinic acid (^99mTc-DMSA). Using a standard questionnaire, demographics, number, size and location of stones, procedure details, outcome as indicated by clearance with PCNL alone or additional procedures, and follow up were documented. Presence of focal renal damage and its association with the PCNL tract were examined.ResultsOut of 60 renal units, cortical defects on ^99mTc-DMSA scan were seen in 10 renal units (17%). In three of these kidneys, the site of focal defect corresponded to the access site for tract formation during PCNL. Two additional kidneys had scarring at multiple sites, one of which corresponded to the access site during PCNL. In the remaining five kidneys no association between focal renal damage and nephrostomy tract site could be ascertained. No association was seen between renal damage and the size of nephroscope used during PCNL.ConclusionThere exists a risk of focal damage to renal parenchyma from the formation of the nephrostomy tract. In our series, focal damage was seen in 5% of patients; this may be an overestimate since preoperative ^99mTc-DMSA scans were not available for our patients. Meticulous technique is important combined with a smaller nephroscope to minimize renal damage. Long-term follow up of such children is required to assess how many are left with permanent renal scars.     

Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells

The efficiency of the mucociliary clearance (MCC) process that removes noxious materials from airway surfaces depends on the balance between mucin secretion, airway surface liquid (ASL) volume, and ciliary beating. Effective mucin dispersion into ASL requires salt and water secretion onto the mucosal surface, but how mucin secretion rate is coordinated with ion and, ultimately, water transport rates is poorly understood. Several components of MCC, including electrolyte and water transport, are regulated by nucleotides in the ASL interacting with purinergic receptors. Using polarized monolayers of airway epithelial Calu-3 cells, we investigated whether mucin secretion was accompanied by nucleotide release. Electron microscopic analyses of Calu-3 cells identified subapical granules that resembled goblet cell mucin granules. Real-time confocal microscopic analyses revealed that subapical granules, labelled with FM 1-43 or quinacrine, were competent for Ca²⁺-regulated exocytosis. Granules containing MUC5AC were apically secreted via Ca²⁺-regulated exocytosis as demonstrated by combined immunolocalization and slot blot analyses. In addition, Calu-3 cells exhibited Ca²⁺-regulated apical release of ATP and UDP-glucose, a substrate of glycosylation reactions within the secretory pathway. Neither mucin secretion nor ATP release from Calu-3 cells were affected by activation or inhibition of the cystic fibrosis transmembrane conductance regulator. In SPOC1 cells, an airway goblet cell model, purinergic P2Y₂ receptor-stimulated increase of cytosolic Ca²⁺ concentration resulted in secretion of both mucins and nucleotides. Our data suggest that nucleotide release is a mechanism by which mucin-secreting goblet cells produce paracrine signals for mucin hydration within the ASL.     

Pretransplant psychiatric and medical comorbidity of alcoholic liver disease patients who received liver transplant

The authors examined the pretransplant prevalence of comorbid physical and psychological disorders in 112 alcoholic liver disease patients who received liver transplant. Fifty-six percent of the patients had comorbid hepatitis C or hepatitis B virus, 40% had used other substances in addition to alcohol, 25% met the criteria for a lifetime DSM-IV nonalcohol substance use disorder, 36% for a lifetime depressive disorder, and 12% for a lifetime anxiety disorder. The findings suggest the need for pretransplant psychiatric evaluation of alcoholic liver disease patients to identify nonalcohol substance use disorders and other psychiatric disorders that may require treatment.     

Donor egg IVF model to assess ecological implications for ART success

PurposeEnvironmental influences on reproductive success are recognized. We hypothesized that location of fertility clinics may influence treatment success and explored this hypothesis utilizing donor egg IVF (IVF) embryo transfer (ET) model.MethodsPublicly accessible national registry data (Society for Assisted Reproductive Technology) on fresh & frozen (FET) ET cycles undertaken at participating clinics across North America (n = 444 IVF centers) for 2007 were utilized. Information on number of donor egg IVF cycles, live birth (LB) rate following fresh and frozen ET(FET), average number (#) of ET and IVF center''s location, geographical coordinates (latitude, longitude, altitude), annualized average temperatures and midyear regional ultraviolet B (UVB) radiation intensity were obtained. Multivariable logistic regression analyses assessed relationship between LBR (in tertile and uppermost versus lesser quartiles) following fresh and FET with geographical coordinates (region and altitude of clinic location) and ecological influences (average temperature and midyear UVB intensity), adjusting for #ET and clinic experience with donor egg IVF.ResultsAverage number of fresh ET, clinic location (region) and midyear UVB intensity were positive predictors of LBR following fresh ET, whereas altitude and annualized average regional temperature demonstrated an inverse relationship with LBR following fresh ET. For FET cycles, #ET, clinic region and altitude were positive determinants of increasing LBR’s. Annualized regional temperature and midyear UVB failed to demonstrate any relationship with LB following donor egg FET.ConclusionOur data suggest that ecological influences may relate to donor egg IVF cycle success. Future studies are needed to better elucidate the mechanisms that could explain the observed associations.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-014-0322-0) contains supplementary material, which is available to authorized users.     

Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia

Trophoblast cell invasion into the uterus is an essential process for successful pregnancy, and shallow invasion of trophoblasts into the maternal decidua is linked to preeclampsia. We have reported that Nodal, a member of the transforming growth factor-β superfamily, acts through activin receptor-like kinase 7 (ALK7) to inhibit trophoblast proliferation and to induce apoptosis. In this study, we examined the spatial and temporal expression patterns of Nodal and ALK7 in human placenta from normal and preeclamptic pregnancies and investigated whether Nodal regulated trophoblast migration and invasion. Nodal and ALK7 were detected in villous and extravillous trophoblast cell populations in early gestation, and their levels were strongly up-regulated in preeclamptic placenta. Overexpression of Nodal or constitutively active ALK7 decreased cell migration and invasion, whereas knockdown of Nodal and ALK7 had the opposite effects. In placental explant culture, treatment with Nodal inhibited trophoblast outgrowth, whereas Nodal small-interfering RNA strongly induced the expansion of explants and the migration of extravillous trophoblast cells. Nodal stimulated the secretion of tissue inhibitor of metalloproteinase-1 and inhibited matrix metalloproteinase (MMP)-2 and MMP-9 activity. These findings suggest that the Nodal/ALK7 pathway plays important roles in human placentation and that its abnormal signaling may contribute to the development of preeclampsia.