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Background: Challenges still exist in differentiating pancreatic adenocarcinoma from benign disease. The use of adjuvant testing of tissue biopsies has demonstrated potential diagnostic value. We designed a proof of concept study to first validate four individual immunohistochemistry biomarkers and then combine them into a panel to boost overall diagnostic sensitivity., Methods: Malignant and benign pancreas from 27 pancreaticoduodenectomy specimens underwent immunohistochemistry staining with VHL, IMP3, S100A4, S100P. Using ROC curve analysis, threshold criteria for number of cells staining were chosen for each biomarker. Biomarkers were then evaluated as a panel for their ability to discriminate malignant from benign specimens., Results: Diagnostic sensitivity of VHL, IMP3, S100A4, and S100P were 75.0%, 79.2%, 45.8%, and 0%. When VHL, IMP3, and S100A4 were grouped into a panel, they were able to distinguish cancer from normal tissue with a sensitivity of 100% and a specificity of 96%., Conclusions: The high diagnostic value of an IHC panel consisting of VHL, IMP3, and S100A4 on surgical specimens suggests the need for future prospective studies of these biomarkers on biopsy specimens., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The role for 1,25-dihydroxyvitamin D3 and/or calcium in hair follicle cycling is not clear despite their impact on keratinocyte differentiation. We found that calbindin-D9k null (knockout) pups generated from calbindin-D9k knockout females fed a vitamin D-deficient, low-calcium (0.47%) diet develop transient alopecia. The pups appear phenotypically normal until 13 days of age, after which the hair progressively sheds in a caudocephalic direction, resulting in truncal alopecia totalis by 20-23 days, with spontaneous recovery by 28 days. Histological studies showed markedly dystrophic hair follicles, loss of hair shafts with increased apoptosis, and hyperplastic epidermis during this time. Ha1 expression is lost during catagen in all mice but recovers more slowly in the knockout pups on the vitamin D-deficient, low-calcium diet. Keratin 1 expression is reduced throughout days 19-28. The expressions of involucrin, loricrin, and cathepsin L is initially increased by day 19 but subsequently falls below those of controls by day 23, as does that of desmoglein 3. Feeding the mothers a high-vitamin D/high-calcium (2%)/lactose (20%) diet lessens the phenotype, and knockout pups fostered to mothers fed a normal diet do not develop alopecia. Our results show that in calbindin-D9k knockout pups, a maternal vitamin D-deficient/low-calcium diet leads to transient noncicatricial alopecia., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Successful reconstruction of large anterior skull base (ASB) defects after craniofacial resection of malignant skull base tumors is paramount for preventing cerebrospinal fluid (CSF) fistulas. The vascularized pedicled pericranial flap (PCF) has been the gold standard for repairing ASB defects after transbasal transcranial approaches. However, flap necrosis and delayed CSF leaks can occur after adjuvant radiation therapy. We describe a "double flap" reconstruction technique in which the PCF is augmented inferiorly by a secondary vascularized pedicled nasoseptal flap (NSF) that is harvested and rotated using an endoscopic endonasal approach., Methods: This technique is illustrated in 2 patients who underwent a combined cranionasal (transbasal and endoscopic endonasal) approach for large sinonasal malignancies with significant intracranial extension (1 esthesioneuroblastoma, 1 sinonasal teratocarcinosarcoma). After tumor removal via a combined cranionasal approach, primary repair of the ASB dural defect was performed with a free patch graft. The ASB defect was then repaired using the double flap technique with a vascularized PCF from above and augmented with a vascularized NSF from below., Results: Postoperatively, there were no complications of CSF leakage, meningitis, or tension pneumocephalus in both patients. After subsequent radiation therapy, the double flap repair remained intact at 2 years postoperatively in both patients., Conclusion: The double flap skull base reconstruction technique provides an additional barrier of vascularized tissue to prevent CSF leakage, meningitis, tension pneumocephalus, and postradiation necrosis. This technique is a viable option if a combined transcranial and transnasal endoscopic tumor resection is performed and postoperative radiation is anticipated., (© 2013 ARS-AAOA, LLC.)

The biologically active metabolite of vitamin D, 1,25(OH)(2)D(3), affects mineral homeostasis and has numerous other diverse physiologic functions including effects on growth of cancer cells and protection against certain immune disorders. This article reviews the role of vitamin D hydroxylases in providing a tightly regulated supply of 1,25(OH)(2)D(3). The role of extrarenal 1α(OH)ase in placenta and macrophages is also discussed, as well as regulation of vitamin D hydroxylases in aging and chronic kidney disease. Understanding specific factors involved in regulating the hydroxylases may lead to the design of drugs that can selectively modulate the hydroxylases. The ability to alter levels of these enzymes would have therapeutic potential for the treatment of various diseases, including bone loss disorders and certain immune diseases., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Increased calcium transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is involved in intestinal calcium transport. To investigate prolactin as a hormone involved in calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)(2)D(3), prolactin, or prolactin + 1,25(OH)(2)D(3). Prolactin alone (1 microg/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D(9k). Combined treatment with 1,25(OH)(2)D(3) and prolactin resulted in an enhancement of the 1,25(OH)(2)D(3) induction of duodenal TRPV6 mRNA, calbindin-D(9k) mRNA, and an induction of duodenal calcium transport [P < 0.05 compared with 1,25(OH)(2)D(3) alone]. Because lactation is associated with an increase in circulating 1,25(OH)(2)D(3), experiments were done to determine whether prolactin also has a direct effect on induction of 25-hydroxyvitamin D(3) 1alpha hydroxylase [1alpha(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1alpha(OH)ase promoter -1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1alpha(OH)ase. In addition, in prolactin receptor transfected AOK B-50 cells, prolactin treatment (400 ng/ml) and signal transducer and activator of transcription 5 significantly induced 1alpha(OH)ase protein as determined by Western blot analysis. Thus, prolactin, by multiple mechanisms, including regulation of vitamin D metabolism, induction of TRPV6 mRNA, and cooperation with 1,25(OH)(2)D(3) in induction of intestinal calcium transport genes and intestinal calcium transport, can act as an important modulator of vitamin D-regulated calcium homeostasis.

The biologically active metabolite of vitamin D, 1,25(OH)(2)D(3), affects mineral homeostasis and has numerous other diverse physiologic functions including effects on growth of cancer cells and protection against certain immune disorders. This article reviews the role of vitamin D hydroxylases in providing a tightly regulated supply of 1,25(OH)(2)D(3). The role of extrarenal 1alpha(OH)ase in placenta and macrophages is also discussed, as well as regulation of vitamin D hydroxylases in aging and chronic kidney disease. Understanding specific factors involved in regulating the hydroxylases may lead to the design of drugs that can selectively modulate the hydroxylases. The ability to alter levels of these enzymes would have therapeutic potential for the treatment of various diseases, including bone loss disorders and certain immune diseases., (Copyright 2010 Elsevier Inc. All rights reserved.)