Suguru Hamada

The osteo-odonto-keratoprosthesis (OOKP).

The osteo-odonto-keratoprosthesis (OOKP), although described over 40 years ago, remains the keratoprosthesis of choice for end-stage corneal blindness not amenable to penetrating keratoplasty. It is particularly resilient to a hostile environment such as the dry keratinized eye resulting from severe Stevens-Johnson syndrome, ocular cicatricial pemphigoid, trachoma, and chemical injury. Its rigid optical cylinder gives excellent image resolution and quality. The desirable properties of the theoretical ideal keratoprosthesis is described. The indications, contraindications, and patient assessment (eye, tooth, buccal mucosa, psychology) for OOKP surgery are described. The surgical and anaesthetic techniques are described. Follow-up is life-long in order to detect and treat complications, which include oral, oculoplastic, glaucoma, vitreo-retinal complications and extrusion of the device. Resorption of the osteo-odonto-lamina is responsible for extrusion, and this is more pronounced in tooth allografts. Regular imaging with spiral-CT or electron beam tomography can help detect bone and dentine loss. The optical cylinder design is discussed. Preliminary work towards the development of a synthetic OOKP analogue is described. Finally, we describe how to set up an OOKP national referral center.

Mesenchymal progenitor cells in adult human dental pulp and their ability to form bone when transplanted into immunocompromised mice

The technique of tissue engineering is developing for the restoration of lost tissues. This new technique requires cells that fabricate tissue. Mesenchymal stem cells in bone marrow have been used as the cell source for this technique; however, dental pulp cells have recently been shown to possess stem‐cell‐like properties.

Osteo-odonto-keratoprosthesis in Japan.

Osteo-odonto-keratoprosthesis (OOKP) is a keratoprosthesis technique in which the patients own tooth root is used to support an optical cylinder. It was invented by Strampelli in 1963 and modified and established by Falcinelli about 10 years later. This method is particularly useful for restoring sight in end-stage Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). We started performing OOKP surgery in June 2003 supported by Dr Christopher Liu of Sussex Eye Hospital, Brighton, UK. Till now, we have performed 4 OOKP surgeries for end-stage SJS and OCP. We modified the original method by using artificial buccal mucous membranes to the bone and buccal mucous membrane defects for better wound healing. Case 1 was a 49-year-old woman (SJS), and the corrected visual acuity was 0.5 in 4 years 8 months. Case 2 was a 68-year-old woman (SJS), and the corrected visual acuity was 0.04 in 3 years 10 months. Case 3 was a 63-year-old man (SJS), and the corrected visual acuity was 0.1 in 3 years 2 months. Case 4 was a 71-year-old woman (OCP), and the corrected visual acuity was 0.04 in 1 year 3 months. Despite some minor optical cylinder troubles such as MRSA colonization, tilting, and buccal mucous coverage, their visual acuities were stable without any serious complications. It was demonstrated that OOKP is useful for visual rehabilitation and durable with minimum eye care for severe ocular surface diseases.

A Case of Severe Stevens-Johnson Syndrome Successfully Treated by Osteo-odonto-keratoprosthesis Surgery

It is difficult to treat severe Stevens-Johnson syndrome (SJS) patients with completely dry ocular surfaces, even using corneal transplantation with amniotic membrane and limbal grafts. For such cases, osteo-odontokeratoprosthesis (OOKP), which was first described by Strampelli, and Falcinelli et al., is a useful method for visual rehabilitation. We believe OOKP can be performed without prior surgery. OOKP is usually a two-stage procedure. In stage one, an optical cylinder is cemented onto the patient’s own tooth root (OOKP lamina) and kept in a submuscular pocket for 2 to 4 months. Buccal mucous membrane is grafted to create a new ocular surface. In stage two, the OOKP lamina is retrieved and surrounding excess soft tissue is removed.The lamina is then implanted between the buccal mucous membrane and the cornea, after removing the iris, lens, and anterior vitreous.Through the fixed optical cylinder, the patient recovers vision (Fig. 1). In this report, we describe the first successful case of OOKP surgery in Japan, with our original modification.

Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC

The prognosis for patients with advanced esophageal or head-and-neck squamous cell carcinoma (ESCC or HNSCC) remains poor, and the identification of additional oncogenes and their inhibitors is needed. In this study, we evaluated the sensitivities of several ESCC and HNSCC cell lines to HER inhibitors (cetuximab, erlotinib, and afatinib) in vitro and found two cell lines that were hypersensitive to afatinib. Sequence analyses for the afatinib-targeted HER family genes in the two cell lines revealed that one cell line had a previously reported activating EGFR L861Q mutation, whereas the other had an HER4 G1109C mutation of unknown function. No amplification of HER family genes was found in either of the two cell lines. The phosphorylation level of HER4 was elevated in the HER4 G1109C mutation-overexpressed HEK293 cell line, and the mutation had a transforming potential and exhibited tumorigenicity in an NIH3T3 cell line, indicating that this HER4 mutation was an activating oncogenic mutation. Afatinib dramatically reduced the phosphorylation level of EGFR or HER4 and induced apoptosis in the two cell lines. In vivo, tumor growth was also dramatically decreased by afatinib. In a database, the frequencies of HER family gene mutations in ESCC or HNSCC ranged from 0% to 5%. In particular, HER4 mutations have been found relatively frequently in HNSCC. Considering the addiction of cancer cells to activating oncogenic EGFR or HER4 mutations for proliferation, HNSCC or ESCC with such oncogenic mutations might be suitable for targeted therapy with afatinib. Mol Cancer Ther; 15(8); 1988–97. ©2016 AACR.

Suppurative arthritis of the temporomandibular joint associated with bisphosphonate: a case report.

a o The prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) has recently increased, and this condition is difficult to manage. A patient is diagnosed with BRONJ if the following 3 characteristics are present: 1) current or previous treatment with a bisphosphonate (BP), 2) exposed bone in the maxillofacial region that has persisted for more than 8 weeks, and 3) no history of radiotherapy of the jaws. BPs are potent inhibitors of osteoclastic bone resorption for the control of hypercalcemia associated with malignancy, multiple myeloma, metastatic bone disease, and bone loss resulting from breast cancer treatment. Other well-established indications are osteoporosis and Paget disease of bone. Suppurative arthritis of the temporomandibular joint (TMJ) is not common. It arises either from hematogenous spread of microorganisms through the highly vascularized synovial membrane or from direct extension of contiguous infection. Several cases have been reported in the literature, and most of hem are associated with predisposing factors. Supurative arthritis of the TMJ has multiple etiologies ncluding trauma, head and neck infection, extraction f a third molar, TMJ arthrosis, or TMJ arthroscopy. Suppurative arthritis of the TMJ associated with BP dministration has not been previously reported. We resent a rare case of suppurative arthritis of the TMJ

Development of resurgent and persistent sodium currents in mesencephalic trigeminal neurons

Sodium channels play multiple roles in the formation of neural membrane properties in mesencephalic trigeminal (Mes V) neurons and in other neural systems. Mes V neurons exhibit conditional robust high‐frequency spike discharges. As previously reported, resurgent and persistent sodium currents (INaR and INaP, respectively) may carry small currents at subthreshold voltages that contribute to generation of spike firing. These currents play an important role in maintaining and allowing high‐frequency spike discharge during a burst. In the present study, we investigated the developmental changes in tetrodotoxin‐sensitive INaR and INaP underlying high‐frequency spike discharges in Mes V neurons. Whole‐cell patch‐clamp recordings showed that both current densities increased one and a half times from postnatal day (P) 0–6 neurons to P7–14 neurons. Although these neurons do not exhibit subthreshold oscillations or burst discharges with high‐frequency firing, INaR and INaP do exist in Mes V neurons at P0–6. When the spike frequency at rheobase was examined in firing Mes V neurons, the developmental change in firing frequency among P7–14 neurons was significant. INaR and INaP density at −40 mV also increased significantly among P7–14 neurons. The change to an increase in excitability in the P7–14 group could result from this quantitative change in INaP. In neurons older than P7 that exhibit repetitive firing, quantitative increases in INaR and INaP density may be major factors that facilitate and promote high‐frequency firing as a function of age in Mes V neurons.

Four Patients Undergoing Labioplasty and Lip Reconstruction for Lip Deformity

We managed four patients who had neoplastic, posttraumatic, atrophic and postoperative lip deformity, respectively. Case 1: The patient had a hemangioma (17 × 14 mm) confined to the vermilion part of the lower lip. We performed the wedge excision of the tumor and labioplasty. The postoperative appearance and function of the lip were satisfactory. Case 2: The patient had posttraumatic deformity of the upper lip. We performed correction by Cronin’s triangular flap method. The postoperative appearance of the lip was satisfactory. Case 3: The patient had severe atrophy of the upper lip and difficulty closing mouth due to progressive hemifacial atrophy. We performed reconstruction of the upper lip on the atrophic side with a cross-lip vermilion flap from the non-atrophic lower lip. The postoperative appearance and function of the lip were satisfactory. Case 4: The patient had postoperative lower lip deformity and difficulty closing mouth after tumor resection and reconstruction with a myocutaneous pectoralis major flap. We performed debulking of the bulky flap and covered the raw surface with a local rotation flap. The postoperative lip closure was satisfactory. In patients with lip deformity, it is important to perform appropriate correction or reconstruction according to each patient’s clinical features in order to achieve satisfactory cosmetic and functional outcomes.

A national opinion study supports tobacco cessation by oral health professionals in Japan

Background: Oral health professionals (OHPs) could have an important role in contributing to tobacco-dependence treatment of patients who visit dental clinics. How the public may perceive the role of OHPs in this capacity, however, has not been formally evaluated. The objective of this study was to assess national awareness and receptivity among Japanese in terms of the implementation of tobacco cessation counseling and treatment (TCCT) by OHPs in dental settings covered by National Health Insurance (NHI). The study participants’ awareness and knowledge on tobacco-related health disparities were also examined. Method: A questionnaire survey was used to assess the opinions among patients who visited hospital dental and oral and maxillofacial departments and private dental clinics (n = 27) spread across several prefectures in Japan on their acceptance if tobacco cessation services were given by dentists and dental hygienists. Result: Overall, 963 survey sheets were eligible for the analysis. To the inquiry on tobacco-related oral diseases (TRODs), majority were aware of tooth staining (85%) and bad breathe (80%). However, less than half of respondents were aware of oral cancer (47%) and only 32% of oral precancer. OHPs were acceptable to the majority of respondents for TCCT: ≥70 age-group (84%), ex-smokers (84%) or never smokers (81%), never drinkers (83%), and students (86%). Paradoxically, current smokers (60%) were less likely to accept OHP for TCCT. However, those willing to quit within a month (89%) were willing to accept any help from OHP than those with no decision to quit (58%) (p = 0.029). Conclusion: The result of this nationwide survey in Japan supported an expansion of duties of OHPs to provide TCCT to dental patients covered by NHI. Japanese patients who were willing to quit smoking were likely to accept TCCT in a dental setting, supporting the scheme for the introduction of tobacco control in dentistry.

Effectiveness of an Interdisciplinary Medical Hospital Admission Center: The Role of the Dental Section in the Interdisciplinary System for Perioperative Management of Patients Awaiting Surgery

Perioperative oral functional management (POFM) involves total oral management of a patient before surgery. Considerable benefits have been reported, but POFM remains scarce in medical settings. An interdisciplinary Medical Hospital Admission Center (MHAC) opened in our hospital in December 2014, and has since provided unified perioperative management for patients. This study reports on the clinical system and contributions of the systematized, standardized POFM applied through the MHAC. Patients awaiting surgery undergo oral screening before admission, with patients classified into three groups: red, needing surgical oral management (tooth extraction or other oral surgery) before surgery; yellow, needing non-surgical oral management before surgery, due to the planned surgery or the risk of tooth injury in connection with general anesthesia; or green, patients with good oral hygiene considered capable of suitable oral self-management. Patients categorized as red or yellow undergo POFM in the dental section of the MHAC before surgery. Almost all patients (88.8%) awaiting surgery now undergo preoperative oral screening, excluding emergent surgeries. In addition, oral screening is important for preventing tooth injury during endotracheal intubation for general anesthesia, and a need for preventive measures was identified in 6.1% of patients. No traumatic injuries of the teeth in connection with general anesthesia have occurred since the opening of the MHAC. Standardized POFM through an interdisciplinary MHAC thus seems extremely useful.