Recalcitrant Invasive Skin Cancer of the Scalp: Combined Extirpation and Microsurgical Reconstruction Without Cranioplasty.

BACKGROUND: Recurrent invasive skin cancer of the scalp and calvarium is a difficult problem for which universally accepted treatment protocols have not been established. The authors present their 10-year experience with treatment of this specific subset of scalp reconstruction patients and present a successful treatment algorithm that is well suited to this patient population. METHODS: The authors retrospectively reviewed all patients of microsurgical scalp reconstruction performed from 2005 to 2015 that involved invasive cutaneous malignancies of the scalp and calvarium. RESULTS: Eleven patients met inclusion criteria. There were 9 squamous cell carcinoma, 1 basal cell carcinoma, and 1 melanoma. Seven received radiation prior to resection, 2 were irradiated postoperatively, and 2 were immunosuppressed. Seven had a history of prior scalp reconstruction. The median scalp defect size was 141 cm. All the patients underwent craniectomy and the median cranial defect size was 71 cm. Cranioplasty was not performed in any patient. There were no intraoperative complications or flap loss. Recipient site complications included hematoma in 1, 1 seroma, 2 cerebral spinal fluid leaks, 3 partial skin graft loss. There was 1 donor site seroma in a patient who had a latissimus dorsi flap. All the patients reported satisfaction with the overall result and none were limited in activities by the existing cranial defect. CONCLUSIONS: This is the largest series published to date that focuses exclusively on management of cutaneous malignancies with intracranial invasion. Wide resection with craniectomy, and reconstruction with microvascular free tissue transfer without cranioplasty provides safe and reliable treatment of recalcitrant invasive scalp skin cancers with low morbidity and without major complications. Pre and postoperative radiation is well tolerated with this approach. The patients in this series were of advanced age and of a lifestyle for which cranioplasty is unnecessary for return to regular activities.

Opioid Prescribing and Use Patterns in Postsurgical Facial Trauma Patients.

BACKGROUND: Facial fractures are painful injuries routinely managed by opioids after surgical repair. Studies have identified patient risk factors and prescribing patterns associated with opioid use in medicine and general surgery; however, little is known about these entities in the facial trauma population. METHODS: A retrospective cohort study of opioid-naive patients undergoing surgical repair of facial fractures was conducted using the Truven Health MarketScan Commercial Claims and Encounters (2006 to 2015) and Medicaid Multi-State Databases (2011 to 2015). Eligible procedures included nasal, nasoorbitoethmoid, orbital, mandible, and Le Fort fracture repair. Opioid type, daily dosage, and prescription duration were analyzed. Multivariable logistic regression was performed to determine independent predictors of prescription refill. RESULTS: A total of 20,191 patients undergoing surgical repair of facial fractures were identified. Of these, 15,861 patients (78.6 percent) filled a perioperative opioid prescription. Refill (58.7 percent) and potentially inappropriate prescribing (39.4 percent) were common among this population. Patient factors including prior substance use (adjusted OR, 1.84; 95 percent CI, 1.63 to 2.07) and history of mental health disorder (adjusted OR, 1.43; 95 percent CI, 1.06 to 1.91) were independent predictors of refill. Increased odds of refill were seen in patients prescribed tramadol (OR, 1.98; 95 percent CI, 1.48 to 2.66) and those who underwent multiple surgical repairs (OR, 3.38; 95 percent CI, 2.54 to 4.50). CONCLUSIONS: Refill and potentially inappropriate prescribing occurred at high rates in facial trauma patients undergoing surgical repair. Additional studies are needed to develop guidelines for proper opioid prescribing in this population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Nasal Bone Osteotomies with Nonpowered Tools.

Controlling the shape of the nasal bones has long been a frustrating problem. Conventional osteotomies are associated with bleeding, loss of reduction, inability to achieve the desired alignment, improperly placed osteotomy sites, and spicule formation. A nonpowered osteotomy method empirically provided the safest and most controlled technique to achieve the desired anatomic result. The nasal bones should be thought of as 2 thin nasal plates that can be released from their medial and lateral attachments to become mobile units that can affect the dorsal width and bony base independently. There is a learning curve to osteotomies.

Factors influencing the titer and infectivity of lentiviral vectors.

Lentiviral vectors have undergone several generations of design improvement to enhance their biosafety and expression characteristics, and have been approved for use in human clinical studies. Most preclinical studies with these vectors have employed easily assayed marker genes for the purpose of determining vector titers and transduction efficiencies. Naturally, the adaptation of these vector systems to clinical use will increasingly involve the transfer of genes whose products may not be easily measured, meaning that the determination of vector titer will be more complicated. One method for determining vector titer that can be universally employed on all human immunodeficiency virus type 1-based lentiviral vector supernatants involves the measurement of Gag (p24) protein concentration in vector supernatants by immunoassay. We have studied the effects that manipulation of several variables involved in vector design and production by transient transfection have on vector titer and infectivity. We have determined that manipulation of the amount of transfer vector, packaging, and envelope plasmids used to transfect the packaging cells does not alter vector infectivity, but does influence vector titer. We also found that modifications to the transfer vector construct, such as replacing the internal promoter or transgene, do not generally alter vector infectivity, whereas inclusion of the central polypurine tract in the transfer vector increases vector infectivity on HEK293 cells and human umbilical cord blood CD34+ hematopoietic progenitor cells (HPCs). The infectivities of vector supernatants can also be increased by harvesting at early time points after the initiation of vector production, collection in serum-free medium, and concentration by ultracentrifugation. For the transduction of CD34+ HPCs, we found that the simplest method of increasing vector infectivity is to pseudotype vector particles with the RD114 envelope instead of vesicular stomatitis virus G glycoprotein (VSV-G).

The Moloney murine leukemia virus repressor binding site represses expression in murine and human hematopoietic stem cells.

The Moloney murine leukemia virus (MLV) repressor binding site (RBS) is a major determinant of restricted expression of MLV in undifferentiated mouse embryonic stem (ES) cells and mouse embryonal carcinoma (EC) lines. We show here that the RBS repressed expression when placed outside of its normal MLV genome context in a self-inactivating (SIN) lentiviral vector. In the lentiviral vector genome context, the RBS repressed expression of a modified MLV long terminal repeat (MNDU3) promoter, a simian virus 40 promoter, and three cellular promoters: ubiquitin C, mPGK, and hEF-1a. In addition to repressing expression in undifferentiated ES and EC cell lines, we show that the RBS substantially repressed expression in primary mouse embryonic fibroblasts, primary mouse bone marrow stromal cells, whole mouse bone marrow and its differentiated progeny after bone marrow transplant, and several mouse hematopoietic cell lines. Using an electrophoretic mobility shift assay, we show that binding factor A, the trans-acting factor proposed to convey repression by its interaction with the RBS, is present in the nuclear extracts of all mouse cells we analyzed where expression was repressed by the RBS. In addition, we show that the RBS partially repressed expression in the human hematopoietic cell line DU.528 and primary human CD34(+) CD38(-) hematopoietic cells isolated from umbilical cord blood. These findings suggest that retroviral vectors carrying the RBS are subjected to high rates of repression in murine and human cells and that MLV vectors with primer binding site substitutions that remove the RBS may yield more-effective gene expression.