Changes in maxillofacial morphology and velopharyngeal function with two-stage maxillary distraction-mandibular setback surgery in patients with cleft lip and palate.

Maxillary distraction is increasingly used for the correction of severe maxillary retrusion in patients with cleft lip and palate. However, control of the maxillary movement is difficult, and the need to wear visible distractors for a long period of time causes psychosocial problems. A two-stage surgical approach consisting of maxillary distraction and mandibular setback was developed to overcome these problems. In this study, changes in maxillofacial morphology and velopharyngeal function were examined in 22 patients with cleft lip and palate who underwent this two-stage approach. Lateral cephalograms taken just before the first surgery, immediately after the second surgery, and at completion of the active post-surgical orthodontic treatment were used to examine maxillofacial morphology. Velopharyngeal function was evaluated by speech therapists using a 4-point scale for hypernasality. The average forward movement of the maxilla with surgery at point A was 7.5mm, and the average mandibular setback at pogonion was 8.6mm. The average relapse rate during post-surgical orthodontic treatment was 25.2% for the maxilla and 11.2% for the mandible. After treatment, all patients had positive overjet, and skeletal relapse was covered by tooth movement during postoperative orthodontics. Velopharyngeal function was not changed by surgery. This method can shorten the period during which the distractors have to be worn and reduce the patient burden.

Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients.

Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma. EGFR mutants were previously shown to exhibit ligand-independent activation. We have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD) suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. We herein demonstrate that SFTPD downregulates ligand-independent signaling in cells harboring EGFR mutations such as TKI-sensitive exon 19 deletion (Ex19del) and L858R mutation as well as TKI-resistant T790M mutation, subsequently suppressing cellular growth and motility. Lectin blotting and ligand blotting in lung cancer cell lines suggested that EGFR mutants express oligomannose-type N-glycans and interact with SFTPD directly. Cross-linking assay indicated that SFTPD inhibits ligand-independent dimerization of EGFR mutants. We also demonstrated that SFTPD reduced dimerization-independent phosphorylation of Ex19del and T790M EGFR mutants using point mutations that disrupted the asymmetric dimer interface. It was confirmed that SFTPD augmented the viability-suppressing effects of EGFR-TKIs. Furthermore, retrospective analysis of 121 patients with lung adenocarcinoma to examine associations between serum SFTPD levels and clinical outcome indicated that in TKI-treated patients with lung cancer harboring EGFR mutations, including Ex19del or L858R, high serum SFTPD levels correlated with a lower number of distant metastases and prolonged overall survival and progression-free survival. These findings suggest that SFTPD downregulates both TKI-sensitive and -resistant EGFR mutant signaling, and SFTPD level is correlated with clinical outcome. These findings illustrate the use of serum SFTPD level as a potential marker to estimate the efficacy of EGFR-TKIs.

Venous superdrained gastric tube pull-up procedure for hypopharyngeal and cervical esophageal reconstruction reduces postoperative anastomotic leakage and stricture.

Gastric pull-up is a common procedure to reconstruct the continuity of the upper digestive tract after esophageal resection. However, this technique sometimes causes postoperative anastomotic leakage or stricture, resulting from insufficient blood flow at the distal end. To overcome this problem, additional microvascular venous anastomoses were performed. The purpose of this study was to compare the outcomes of post-surgical anastomotic leakage and stricture in patients with and without additional microvascular venous superdrainage after cervical esophageal and hypopharyngeal resection and gastric tube reconstruction. A total of 29 consecutive patients with esophageal or hypopharyngeal cancer who underwent total esophagectomy and hypopharyngectomy with gastric tube reconstruction in the National Organization Nagasaki Medical Center between April 2014 and May 2016 were analyzed in this study. Of these patients, 20 underwent additional venous anastomoses (superdrainage group), and 9 did not undergo additional procedures (standard group). We compared the frequency of post-surgical stricture and leakage in the two groups retrospectively. Three of nine patients (33.3%) developed postoperative leakage in the standard group, and 1 of 20 (5.0%) did so in the superdrainage group. Six of nine patients (66.7%) showed postoperative anastomotic stricture in the standard group, but none did so in the superdrainage group. Patients who did not undergo additional venous superdrainage were significantly more likely to develop postsurgical leakage (P < 0.05, Chi-square test) and anastomotic stricture (P < 0.001, Chi-square test). Our study revealed that only additional venous anastomoses could reduce the incidence of postoperative anastomotic leakage and stricture. This procedure is of merit to perform after total esophagectomy and hypopharyngectomy with gastric tube reconstruction.

A novel method for designing and fabricating custom-made artificial bones.

Artificial bones are useful for tissue augmentation in patients with facial deformities or defects. Custom-made artificial bones, produced by mirroring the bone structure on the healthy side using computer-aided design, have been used. This method is simple, but has limited ability to recreate detailed structures. The authors have invented a new method for designing artificial bones, better customized for the needs of individual patients. Based on CT data, three-dimensional (3D) simulation models were prepared using an inkjet printer using plaster. The operators applied a special radiopaque paraffin wax to the models to create target structures. The wax contained a contrast medium to render it radiopaque. The concentration was adjusted to achieve easy manipulation and consistently good-quality images. After the radiopaque wax was applied, the 3D simulation models were reexamined by CT, and data on the target structures were obtained. Artificial bones were fabricated by the inkjet printer based on these data. Although this new technique for designing artificial bones is slightly more complex than the conventional methods, and the status of soft tissue should also be considered for an optimal aesthetic outcome, the results suggest that this method better meets the requirements of individual patients.

Cyclooxygenase-2 activity is important in craniofacial fracture repair.

The aim of this study was to examine the effect of cyclooxygenase (COX)-2 on bone repair after craniofacial fracture in mice. A 4-mm fracture was created in the parietal bone of 8-week-old male COX-2 wild-type (COX-2(+/+)) and knockout (COX-2(-/-)) mice. Ribonucleic acid was extracted from the fractured bone and analysed. For morphological and histological analysis, the mice were killed 8 and 12 weeks after treatment, and sections were prepared. Three-dimensional computed tomography was performed, and the sections were stained with hematoxylin-eosin for histological examination. Expression of COX-2 messenger ribonucleic acid was induced in COX-2(+/+) mice, but not in COX-2(-/-) mice. Ossification at the fracture site was almost complete 12 weeks after fracture in COX-2(+/+) mice. In COX-2(-/-) mice, incomplete union had occurred at the fracture site. In both types of mice, the fracture site contained no cartilaginous tissue, and the callus formed from the periosteal side. These results suggest that COX-2 plays an important role in craniofacial fracture repair and that COX-2-selective non-steroidal anti-inflammatory drugs might interfere with fracture repair of the membranous viscerocranium in the clinical setting.

Unilateral expansion of a narrow mandibular dental arch combined with bimaxillary osteotomies in a patient with hypoglossia.

A 23-year-old female with hypoglossia, who had a narrow mandibular dental arch, was treated using the gradual expansion technique. Three lower incisors were missing and the right molar occlusion showed a scissor bite. Her speech was acceptable. Gradual unilateral expansion of the mandibular alveolar bone was performed. Orthodontic tooth alignment was performed prior to surgical treatment. A tooth-borne expander was devised using a hyrax-type screw to move the inclined right alveolar bone into an upright position. Alveolar bone osteotomies were performed under general anesthesia and the expander was placed in the mandibular dental arch. After a 5-day latency period, the screw was activated for 21 days. After expansion, the width of the mandibular dental arch increased by 10mm at the first molar region and the right molars were moved to an upright position. After a consolidation period of 7 days, simultaneous two-jaw surgery that combined Le Fort I osteotomy and intraoral vertical ramus osteotomies was performed to obtain a stable occlusion. After post-surgical orthodontic and prosthodontic treatment, her occlusion improved without deterioration of her speech. The results indicate that this technique is useful for unilateral expansion of distorted mandibular alveolar process.

A case of tumoural calcinosis in the temporomandibular joint associated with systemic sclerosis.

Systemic sclerosis (SSc) is a relatively rare condition characterized by the excessive production and deposition of collagen within tissue. This condition is thought to be immunologically mediated and, in addition to its notorious cutaneous manifestations, often involves multiple organs. A case is presented of systemic sclerosis associated with extensive tumoural calcinosis in the temporomandibular joint. There has been no evidence of recurrence or complications during approximately 2 years of follow up, but long-term follow up is essential.

Cyclooxygenase-2 activity is essential for the osseointegration of dental implants.

The aim of this study was to examine the effect of cyclooxygenase (COX)-2 on bone response after the placement of implants in the femurs of mice. titanium implants 1.0mm in diameter were placed into the middle of the femurs of 9-week-old male COX-2 wild-type (COX-2(+/+)) and knockout (COX-2(-/-)) mice. For RNA analysis, the mice were killed 0, 1, 2, 4, 7 and 56 days after implantation. RNA was extracted from the bone surrounding the implants. For histological analysis, the mice were killed 4 and 8 weeks after treatment, and undecalcified sections were prepared. Contact microradiography was performed, and the sections were stained with 1% toluidine blue for histological examination. Histomorphometric measurements were obtained with a computer-based image analyser to quantify bone newly formed around the implant and the rate of implant-bone contact. Expression of COX-2 and osteocalcin mRNA was induced in bone surrounding implants in COX-2(+/+) mice, but not in COX-2(-/-) mice. In cortical bone, the implant surface was in direct contact with newly formed bone lamellae in COX-2(+/+) mice; new bone formation was minimal in COX-2(-/-) mice. These results suggest that COX-2 plays an essential role in osseointegration and provide evidence that COX-2-selective non-steroidal anti-inflammatory drugs may interfere with osseointegration clinically.

A 2-stage procedure combining maxillary advancement by distraction technique with mandibular setback surgery in patients with cleft lip and palate.

A 2-stage procedure combining maxillary advancement by distraction technique with mandibular setback surgery was used to correct jaw deformities in 5 patients with severe maxillary retrusion secondary to cleft lip and palate. First, a Le Fort I maxillary osteotomy was performed. Immediately after maxillary distraction, the distraction device was removed. The advanced maxilla was fixed with miniplates after adjusting the length and direction of advancement, and mandibular setback surgery was performed simultaneously to obtain a normal occlusal relationship. This 2-stage procedure resulted in stable occlusion and a markedly improved facial profile.

[Anesthetic management for gastrojejunostomy in a patient with hemiplegia and recurrent laryngeal nerve palsy].

A 70-year-old man who had undergone a low anterior resection for primary rectal cancer 9 years before complained of anorexia, hemiplegia, and recurrent laryngeal nerve palsy. The anorexia was caused by duodenal stenosis due to swollen lymph nodes, the hemiplegia was caused by a metastatic brain tumor, and the recurrent laryngeal nerve palsy was caused by metastases of the cancer to the mediastinal space. Metastases were also found in the bilateral lungs, liver, ureter, and cervical vertebra. In choosing the anesthesia for the gastrojejunostomy to improve the malnutrition of this patient, we decided, on the basis of the patient's full stomach, malnutrition, hypovolemia, hemiplegia, cerebral compression, recurrent laryngeal nerve palsy, renal dysfunction, and respiratory dysfunction, to use thoracic epidural anesthesia rather than spinal anesthesia or general anesthesia. Thoracic epidural anesthesia could provide sufficient analgesia, and the operation was uneventful. In anesthetic management of an end-stage patient undergoing a palliative operation like this, we should consider the purpose of the operation, its complications, and further complications which may be induced by anesthesia in order to plan out an anesthetic regimen unlikely to lead to harmful events in perioperative period.

[Anesthetic management of a hyper-obese patient by target-controlled infusion (TCI) of propofol and fentanyl].

We gave total intravenous anesthesia to an over-100% hyper-obese patient using target-controlled infusion (TCI) of propofol and fentanyl. To keep him asleep, we maintained his BIS in a range of 40 to 60 by adjusting the target concentration of propofol. For the target concentration of fentanyl, we chose 2 ng.ml-1 at incision and 1.6 ng.ml-1 during the operation. At the patient's emergence from anesthesia, his estimated blood concentration of propofol was 1.51 micrograms.ml-1 and his BIS was 80. The relationship between BIS value and effect-site concentration of propofol was almost the same as that assessed in ordinary adults of a normal weight. We conclude that the estimated concentration of propofol is a good indicator of the effect of propofol and that TCI is a useful technique in obese patients as well as in ordinary adults.

[The effect of intravenous prostaglandin F 2 alpha on the motility of the gastrointestinal tracts after major abdominal surgery (author's transl)].

TThe effect of prostaglandin F 2 alpha was studied clinically and electromyographically on the motility of the gastric antrum, duodenum, jejunum, ileum and transverse colon in 20 patients by giving 2 hours intravenous drip infusion at 0.3 approximately 0.5 microgram/kg/min for 2 hours after major abdominal surgery. Folling results were obtained. 1. The motility of stomach and colon was least active than any other site of alimentary tract during 48 hours after surgery. This seems to be one of the most important causes of so called postoperative ileus. 2. Recovery from reflex inhibition of motility of the alimentary tract after surgery was seen in duodenum at first, and then in jejunum and ileum in order. It was proved that intravenous drip infusion of PGF 2 alpha at 0.3 approximately 0.5 microgram/kg/min for 2 hours had produced the increase of electrical activity in any site of gastrointestinal tract and subsequently brought about increasing of propulsive movement. The effect of PGF 2 alpha is proportional to its concentration. 4. tit was concluded that PGF 2 alpha could be administered most effectively by intravvenous drip infusion at 0.5 microgram/kg/min 3 times daily for 3 days after surgery for the satisfactory recovery from the postoperative ileus, and no appreciable side effect was observed.