Personalized Bioactive Nasal Supports for Postoperative Cleft Rhinoplasty.

PURPOSE: After cleft lip and palate surgical procedures, patients often need nostril supports to help the reconstructed nostrils retain their shape during healing. Many postoperative nasal stents use a one-size-fits-all approach, in which a standard rubber tube retainer is trimmed and used to support the healing nares. The purpose of this study was to examine photogrammetry and 3-dimensional (3D) printing as a fabrication tool for postoperative patient-specific nasal supports that can be loaded with bioactive agents for localized delivery. MATERIALS AND METHODS: A "normal" right nostril injection mold was prepared from a left-sided unilateral cleft defect, and the negative-space impression was modeled using a series of photographs taken at different rotation angles with a commercial mobile phone camera. These images were "stitched" together using photogrammetry software, and the computer-generated models were reflected, joined, and digitally sculpted to generate hollow bilateral supports. Three-dimensional prints were coated with polyvinylpyrrolidone-penicillin and validated for their ability to inhibit Escherichia coli using human blood agar diffusion assays. RESULTS: The results showed that our approach had a high level of contour replication and the antibiotic coating was able to inhibit bacterial growth with a mean zone of inhibition of 15.15 ± 0.99 mm (n = 9) (P < .0001) in disc diffusion assays. CONCLUSIONS: Consumer-grade 3D printing displays potential as a fabrication method for postoperative cleft bilateral nasal supports and may support the surgically reconstructed internal contours. The results of this study suggest that such types of bioactive 3D prints may have potential applications in personalized drug-delivery systems and medical devices.

Metastatic Melanotic Neuroectodermal Tumor of Infancy: Report of a Case and Review of the Literature.

Melanotic neuroectodermal tumors of infancy (MNTI) are rapidly growing pigmented tumors that occur predominantly within bony head and neck structures. There are fewer than 400 cases reported in the literature with the majority affecting the maxilla. Locations in other intraosseous and extraosseous structures have been characterized, including the mandible (6% of MNTIs). Infants in the first year of life are primarily affected. Surgical resection is the primary treatment modality with and without adjuvant chemotherapy for malignant tumors, which comprise less than 25 cases in the literature, and of metatstatic mandibular tumors, which has only been documented in one other case. The purpose of this investigation is to review associated literature and present a case highlighting treatment considerations of a metastatic mandibular MNTI. We present the case of a six month old boy with a rapidly growing bluish mass of the right mandible. Preoperatively incisional biopsy led to a diagnosis of MNTI and subsequent surgical planning involved hemimandibulectomy from the right mandibular condyle to the left posterior body region with one centimeter margins. At the time of initial surgery, enlarged lymph nodes removed from the neck demonstrated abnormality consistent with metastatic spread of the tumor. Islands of tumor cells were noted: small, round, bluestaining cells resembling neuroblasts with mitotic activity as well as pigmented cells containing melanin. Because of regional node metastasis, chemotherapy was completed following surgery. The patient recovered and was followed without evidence of recurrence. At 3.5 years postresection, a secondary reconstruction was completed using a fibula osteocutaneous free flap combined with a costochondral rib graft. In reviewing similar cases of malignant MNTI reported in the literature, a search of the MEDLINE database until 2014 was performed. These were evaluated based on management type and outcome, including surgical and chemotherapeutic treatments and the incidence of recurrence or metastasis.

Oral/Head and Neck Oncologic and Reconstructive Surgery Fellowship Training Programs: Transformation of the Specialty From 2005 to 2015: Report from the AAOMS Committee on Maxillofacial Oncology and Reconstructive Surgery.

Oral and Maxillofacial Surgeons have increasing opportunities to train in head and neck oncologic and reconstructive surgery. The development of a fellowship training programs within our speciality has had a transformative effect on the speciality. This survey by the commitee on Maxillofacial Oncology and Reconstructive is aimed to evaluate the impact of fellowship training on the careers of the fellows and speciality from 2005-2015.

Retrospective analysis of the effects of orthognathic surgery on the pharyngeal airway space.

PURPOSE: Dentofacial deformities can be defined as defects in the growth and development of facial bones, mainly the maxilla and mandible. Such deformities can change the dimension and function of the pharyngeal airway space and orthognathic surgery is the treatment of choice. The aim of this study was to evaluate changes in the pharyngeal airway space after orthognathic surgery and test the ability of cone-beam computed tomographic (CBCT) imaging to allow analysis of the airway. MATERIALS AND METHODS: Pre- and postoperative measurements were taken using CBCT images of 100 patients who underwent orthognathic surgery. RESULTS: The results showed an increase of the airway at the middle portion in the anteroposterior and lateral directions in the maxillary advancement, mandibular advancement, and maxillomandibular advancement groups. The results also showed an increase of total area in the maxillary advancement, mandibular advancement, maxillomandibular advancement, and maxillary advancement and mandibular setback groups. Total sagittal area increased in accord with bone movement. CONCLUSIONS: CBCT imaging allows the analysis of the effects of orthognathic surgery on the pharyngeal airway. Changes to the airway follow the maxillomandibular advancement that is carried out and the maxillary and mandibular advancements increase the upper and middle airway in the anteroposterior and lateral directions.

Ocular Hypertelorism: Principles and Management.

Background: Ocular hypertelorism (OH) was initially considered as un-differentiated congenital cranio-facial deformity, however, I.T Jackson mentioned it as teleorbitism, considering it as increase in the inter-canthal width, inter-pupillary as well as inter-orbital distance as a result of lateralization of the orbital complex in total. Furthermore, Sailer further refined it and included the distance from the lateral orbital wall, i.e. he denoted increased inter-orbital distance along with the distance between lateral orbital walls as true hypertelorism. This condition is rare and is seen in association with midline congenital defects affecting the cranio-facial region. Classification and review of cases: The ideal time for the OH correction is usually between 5 and 8 years of age. However, the management of OH is complex, and several techniques have been described in literature for the same. Here, we describe our classification of OH, along with the evolution of the surgical aspects, the key treatment principles we follow, together with the types of the osteotomies and their indications. Furthermore, we delineate the four main principles that we have set for OH management. Results: Though the improvement in appearance is seen immediately post-surgery, however, this challenging surgery faces a multitude and common postoperative complications which have been represented in this article. The surgeon needs both the technical expertise and an inclination towards aesthetics for the execution of such procedures. Conclusion: It is preferred that the management of OH should be individualized as per the stage of the craniofacial growth and the psychosocial needs of the patient and the parents.

How intensive should radiotherapy for head and neck cancer with synchronous distant metastases be? Review of cases.

PURPOSE: Given the differences in treatment objectives among oncologists and complexities of standards of therapy for advanced head and neck cancer (HNC), we sought to determine whether HNC patients with simultaneous distant metastases (M1) benefit from aggressive therapeutic intervention. MATERIALS AND METHODS: Among the 1,988 patients diagnosed with HNC during a 22-year period, 7 patients with synchronous M1 tumors were identified. Of these individuals, 4 were treated with a prolonged course of radiotherapy for HNC (group A) and 3 were not (group B). RESULTS: The median survival and 60-day mortality rate in group A were 14 months and 0%, respectively, whereas the corresponding observations for group B were 5.5 months and 50%. No difference in HNC stage or M1 extent was present between the 2 groups. The patients composing group A were older than those in group B. CONCLUSION: These data suggest that some benefit may be obtained by the application of a full course of irradiation for HNC with synchronous M1 disease. The practice of intensive radiotherapy for this particular complicated neoplastic condition needs to be reviewed, considering the health care reform and emphasis on cost-effectiveness in the near future.

Bilateral Eagle Syndrome.

Significance StatementUnilateral Eagle Syndrome is relatively rare and highlights important concepts in anatomy and pathophysiology. Bilateral Eagle Syndrome is exponentially more rare and has only been mentioned several times in the literature. Understanding the impact this can have on the human body and the severity of symptoms and sequelae is valuable for several types of specialists that treat this disorder.

Bad Smells and Broken DNA: A Tale of Sulfur-Nucleic Acid Cooperation.

Hydrogen sulfide (H2S) is a gasotransmitter that exerts numerous physiologic and pathophysiologic effects. Recently, a role for H2S in DNA repair has been identified, where H2S modulates cell cycle checkpoint responses, the DNA damage response (DDR), and mitochondrial and nuclear genomic stability. In addition, several DNA repair proteins modulate cellular H2S concentrations and cellular sulfur metabolism and, in turn, are regulated by cellular H2S concentrations. Many DDR proteins are now pharmacologically inhibited in targeted cancer therapies. As H2S and the enzymes that synthesize it are increased in many human malignancies, it is likely that H2S synthesis inhibition by these therapies is an underappreciated aspect of these cancer treatments. Moreover, both H2S and DDR protein activities in cancer and cardiovascular diseases are becoming increasingly apparent, implicating a DDR-H2S signaling axis in these pathophysiologic processes. Taken together, H2S and DNA repair likely play a central and presently poorly understood role in both normal cellular function and a wide array of human pathophysiologic processes. Here, we review the role of H2S in DNA repair.

Molecular Functions of Hydrogen Sulfide in Cancer.

Hydrogen sulfide (H2S) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. H2S-synthesizing enzymes are increased in a variety of human malignancies, including colon, prostate, breast, renal, urothelial, ovarian, oral squamous cell, and thyroid cancers. In cancer, H2S promotes tumor growth, cellular and mitochondrial bioenergetics, migration, invasion, angiogenesis, tumor blood flow, metastasis, epithelia-mesenchymal transition, DNA repair, protein sulfhydration, and chemotherapy resistance Additionally, in some malignancies, increased H2S-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of H2S in cancer, with an emphasis on the molecular mechanisms by which H2S promotes cancer development, progression, dedifferentiation, and metastasis.

Creating the Successful Global Maxillofacial Surgeon: A 35-Year Perspective.

The success of global outreach surgical programs depends on many factors including the preparation of the surgeons involved in the program. Surgeons in preparing for global outreach programs often focus on surgical procedures or techniques as the most important aspect of the preparation for the program. Just as important to success of the outreach program is the surgeon's familiarity with the language, cultural, and social norms of the host country or region. This article provides valuable information on these issues from three oral and maxillofacial surgeons who have been engaged in global oral and maxillofacial surgery outreach programs for decades.

Obturation and Tissue Transfer for Large Craniofacial Defects.

Reconstruction of large craniofacial defects requires several factors to be considered before deciding on the best reconstructive option. This article discusses various factors taken into consideration when deciding on which reconstructive option is ideal for a given patient and defect. For large craniofacial defects, reconstruction using tissue transfer is considered preferentially over obturation, although in select defects obturation using a traditional tooth- or implant-borne prosthetic obturator can be considered a viable option.

Does the negative node count affect disease-free survival in early-stage oral cavity cancer?

PURPOSE: We performed a retrospective study to determine whether there is a relationship between disease-free survival and negative lymph node count in patients with resected early-stage oral cavity cancers. MATERIALS AND METHODS: Of the 526 individuals diagnosed with carcinoma of the oral cavity between 1998 and 2005, 52 had undergone primary tumor resection and lymph node dissection of the neck for stage I or II disease. With a mean count of 27 examined negative nodes, these 52 patients were separated into groups with fewer than 27 or > or = 27 uninvolved lymph nodes and compared for disease-free survival. RESULTS: The tumor recurred or progressed in 10 patients (19%) during a median follow-up of 27 months. The 2-year disease-free survival rates were 75% and 78% in individuals with fewer than 27 and > or = 27 uninvolved node counts, respectively (P > .78). CONCLUSION: The removal of a greater number of regional, uninvolved cervical lymph nodes does not correlate with disease-free survival in this particular cohort of patients.

Maxillofacial Reconstruction Using Vascularized Fibula Free Flaps and Endosseous Implants.

Maxillofacial subunit reconstruction using vascularized fibula free flap and endosseous implants is a complex and exciting topic. Use of this technique has profoundly improved patients' function, form, and quality of life. This article outlines the goals and requirements of reconstruction and patient selection. Current data are examined and issues related to flap selection, irradiation, primary versus secondary implant placement, timing and type of implants, use of virtual surgical planning, soft-tissue management, and prosthesis selection fabrication are discussed. Careful planning, communication, and collaboration between reconstructive surgeons and prosthodontists are critical in achieving optimal and stable long-term outcomes.

The Ataxia telangiectasia-mutated and Rad3-related protein kinase regulates cellular hydrogen sulfide concentrations.

The ataxia telangiectasia-mutated and Rad3-related (ATR) serine/threonine kinase plays a central role in the repair of replication-associated DNA damage, the maintenance of S and G2/M-phase genomic stability, and the promotion of faithful mitotic chromosomal segregation. A number of stimuli activate ATR, including persistent single-stranded DNA at stalled replication folks, R loop formation, hypoxia, ultraviolet light, and oxidative stress, leading to ATR-mediated protein phosphorylation. Recently, hydrogen sulfide (H2S), an endogenous gasotransmitter, has been found to regulate multiple cellular processes through complex redox reactions under similar cell stress environments. Three enzymes synthesize H2S: cystathionine-ß-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase. Since H2S can under some conditions cause DNA damage, we hypothesized that ATR activity may regulate cellular H2S concentrations and H2S-syntheszing enzymes. Here we show that human colorectal cancer cells carrying biallelic knock-in hypomorphic ATR mutations have lower cellular H2S concentrations than do syngeneic ATR wild-type cells, and all three H2S-synthesizing enzymes show lower protein expression in the ATR hypomorphic mutant cells. Additionally, ATR serine 428 phosphorylation is altered by H2S donor and H2S synthesis enzyme inhibition, while the oxidative-stress induced phosphorylation of the ATR-regulated protein CHK1 on serine 345 is increased by H2S synthesis enzyme inhibition. Lastly, inhibition of H2S production potentiated oxidative stress-induced double-stranded DNA breaks in the ATR hypomorphic mutant compared to ATR wild-type cells. Our findings demonstrate that the ATR kinase regulates and is regulated by H2S.

3D Printing for Bio-Synthetic Biliary Stents.

Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. The biofabrication method in the present study examined 3D printing and collagen injection molding for rapid prototyping of customized living biliary stents with clinical applications in the setting of malignant and benign bile duct obstructions. XL-PVA stents showed hydrophilic swelling and addition of radiocontrast to the stent matrix improved radiographic opacity. Collagen loaded with PMSCs contracted tightly around hydrophilic stents and dense choloangiocyte coatings were verified through histology and fluorescence microscopy. It is anticipated that design elements used in these stents may enable appropriate stent placement, provide protection of the stent-stem cell matrix against bile constituents, and potentially limit biofilm development. Overall, this approach may allow physicians to create personalized bio-integrating stents for use in biliary procedures and lays a foundation for new patient-specific stent fabrication techniques.

High-throughput scaffold-free microtissues through 3D printing.

BACKGROUND: Three-dimensional (3D) cell cultures and 3D bioprinting have recently gained attention based on their multiple advantages over two-dimensional (2D) cell cultures, which have less translational potential to recapitulate human physiology. 3D scaffold supports, cell aggregate systems and hydrogels have been shown to accurately mimic native tissues and support more relevant cell-cell interactions for studying effects of drugs and bioactive agents on cells in 3D. The development of cost-effective, high-throughput and scaffold-free microtissue assays remains challenging. In the present study, consumer grade 3D printing was examined as a fabrication method for creation of high-throughput scaffold-free 3D spheroidal microtissues. RESULTS: Consumer grade 3D printing was capable of forming 96-well cell culture inserts to create scaffold-free microtissues in liquid suspensions. The inserts were seeded with human glioblastoma, placental-derived mesenchymal stem cells, and intestinal smooth muscle cells. These inserts allowed for consistent formation of cell density-controllable microtissues that permit screening of bioactive agents. CONCLUSION: A variety of different cell types, co-cultures, and drugs may be evaluated with this 3D printed microtissue insert. It is suggested that the microtissue inserts may benefit 3D cell culture researchers as an economical assay solution with applications in pharmaceuticals, disease modeling, and tissue-engineering.

Cranium Bifidum Occultum Associated with Hypertelorism Treated with Posterior Vault Reconstruction and Orbital Box Osteotomies: Case Report and Technical Note.

Cranium bifidum occultum is a disorder of skull ossification presenting as an enlarged posterior fontanelle in the upper posterior angle of the parietal bone near the intersection of the sagittal and lambdoid sutures. The standard treatment for cranium bifidum occultum is observation. We present a case of a 5-year-old boy who presented with a 15 × 4.5 cm midline posterior cranial vault defect consistent with diagnosis of cranium bifidum occultum associated with orbital hypertelorism and a widened nose. The patient underwent posterior vault reconstruction for correction of cranium bifidum occultum defect followed by bifrontal craniotomy and orbital box osteotomies for correction of orbital hypertelorism and nasal deformity. To our knowledge, this is the first reported case describing surgical treatment for cranium bifidum occultum associated with orbital hypertelorism.