Changes in Quality of Life After Secondary Closure of Palatal Defects: Prosthetic Obturation Versus Surgical Reconstruction.

BACKGROUND: The closure of palatal defects after tumor resection or irradiation is performed with either a prosthesis or autogenous tissue; however, there are no clear criteria regarding selection of the method. Thus, this study aimed to investigate the real-world situation and problems of palatal closure using prostheses, and examined patient opinion on how palatal closure using autogenous tissue improved their postoperative quality of life (QOL). METHODS: In 5 patients whose palatal defects resulted from treatment for head and neck cancer and were closed with a prosthesis, the palate was closed secondarily with autogenous tissue; a questionnaire on daily life was administered pre- and post-operatively. RESULTS: Functional improvements in terms of speech and eating were achieved in all and in 4 of 5 cases, respectively. In all cases, the QOL was better for palatal closure with autogenous tissue than with the prosthesis. CONCLUSIONS: As postoperative QOL was considered to be better when reconstructing the palate with autogenous tissue than with the prosthesis, we recommend to actively select autogenous tissue for palate reconstruction.

Morphological Changes and Durability of Skin and Mucosal Flaps in Intraoral and Pharyngeal Reconstructions: Long-term Follow-up and Literature Review for Potential Second Carcinomas.

The long-term changes in tissues implanted in the oral cavity and pharynx after head and neck reconstruction have not been fully evaluated. This study aimed to clarify the morphological changes, long-term durability, and potential for secondary carcinogenesis in such tissues. In our single-center study, the rough morphological changes in 54 cases of intraoral and pharyngeal skin and mucosal flaps were evaluated more than 10 years after flap transfer. In addition, the literature on the development of second carcinomas from skin flaps was reviewed. The mean follow-up period for transferred flaps was 148 months. The reconstruction areas and the probability of morphological changes were significantly correlated (p=0.006), especially in cases with tongue, lower gingiva, and buccal mucosal reconstruction. Free jejunal flap surfaces were well maintained, whereas tubed skin flaps showed severe morphological changes in cases with pharyngeal reconstruction. None of the flaps in our series developed second primary carcinomas. Skin flaps generally had good durability for > 10 years in intraoral environments, while mucosal flaps had better durability for pharyngeal reconstruction. Second squamous carcinomas arising from skin flaps are extremely rare; however, surgeons should take this possibility into consideration and conduct meticulous and long-term follow-up.

The Incidence of Oral and Oropharyngeal Cancers in Betel Quid-Chewing Populations in South Myanmar Rural Areas.

Oral cancer is a very common disease in South and Southeast Asia. Betel quid (BQ)- chewing and tobaccosmoking habits are etiological factors for oral cancer patients in these regions. We conducted an oral cancer screening in BQ-chewing endemic rural areas in South Myanmar for the early detection of oral cancer in BQ-chewing and smoking individuals. We examined 105 subjects who were at high risk of oral cancer due to their oral habits (BQ users and/or smokers). Three carcinoma cases were detected, and there were 8 dysplasia cases. The carcinoma detection rate was 2.9%, and the carcinoma and precancerous lesion detection rate was 10.5%. In Myanmar, oral cancer screening has been conducted sporadically on a voluntary basis, and nationwide surveys have never been performed. There are also few reports of oral cancer screening for high-risk groups among the general population in Myanmar. Our present findings highlight the need for further screening and surveys. Education on betel quid chewing- and tobacco- related oral diseases and screening for the early detection of oral cancer are of the utmost importance in the control and prevention of oral cancer.

Structure of a New Palatal Plate and the Artificial Tongue for Articulation Disorder in a Patient with Subtotal Glossectomy.

A palatal augmentation prosthesis (PAP) is used to facilitate improvement in the speech and swallowing functions of patients with tongue resection or tongue movement disorders. However, a PAP's effect is limited in cases where articulation disorder is severe due to wide glossectomy and/or segmental mandibulectomy. In this paper, we describe speech outcomes of a patient with an articulation disorder following glossectomy and segmental mandibulectomy. We used a palatal plate (PP) based on a PAP, along with an artificial tongue (KAT). Speech improvement was evaluated by a standardized speech intelligibility test consisting of 100 syllables. The speech intelligibility score was significantly higher when the patient wore both the PP and KAT than when he wore neither (p＝0.013). The conversational intelligibility score was significantly improved with the PP and KAT than without PP and KAT (p＝0.024). These results suggest that speech function can be improved in patients with hard tissue defects with segmental mandibulectomy using both a PP and a KAT. The nature of the design of the PP and that of the KAT will allow these prostheses to address a wide range of tissue defects.

Secondary head and neck reconstruction using free flap to improve the postoperative function or appearance of cancer survivors.

BACKGROUND: Secondary reconstructive operations are needed when patients with head and neck cancers have complications such as tumor recurrence after initial treatment. These reconstructive procedures are also performed to improve the function and appearance of the head and neck region for many cancer survivors. We reviewed the patients who underwent secondary head and neck reconstruction to improve function and appearance and considered the significance of this procedure for cancer survivors, as well as its associated problems. METHODS: Among the secondary reconstruction patients, 20 patients underwent reconstruction to improve their function and/or appearance. The goal of reconstruction for the patients was functional improvement in eight cases, appearance improvement in ten cases, and both function and appearance in two cases. Chi-square analyses were performed between the secondary and primary reconstructive groups with regard to the incidence of postoperative complications. RESULTS: All transferred flaps survived completely. We performed a small postoperative modification procedure in four cases. Minor complications not requiring surgical correction occurred in 2 of 20 patients. Additional operations were required owing to major postoperative complications in 2 of 20 patients. No significant associations were identified between the secondary and primary reconstructive groups with regard to postoperative complications. CONCLUSION: The outcomes of the present report suggest that secondary reconstructive surgery is a relatively safe procedure. The decision to perform adaptation operations depends on various factors after sufficient discussion with patients.

Effects of radiation therapy on postoperative complications and adverse events in patients with head and neck reconstruction with flaps.

BACKGROUND: Radiation therapy is an essential treatment for head and neck cancer. However, the condition of the operative field is entirely altered after radiation therapy. This study aimed to examine the effects of preoperative radiation therapy on complications in patients who underwent head and neck reconstruction with flaps. METHODS: We retrospectively reviewed 252 instances of head and neck reconstruction with flaps in 240 patients between October 2000 and May 2011 at Okayama University Hospital. Of the participants, 51 had preoperative radiation exposure (21.3%) and 189 had no radiation exposure (78.7%). Postoperative complications were divided into three categories: minor complications that healed with conservative medical treatment within 4 weeks without a need for surgery; major complications requiring reoperation within 1 week after surgery (reoperation); and major complications needing additional operation later than 1 week after surgery (additional operation). RESULTS: Preoperative radiation therapy was only associated with major complications requiring reoperation later than 1 week after surgery (P < 0.001), open cervical wounds (P = 0.0030), and skin grafting for cervical skin necrosis (P = 0.0031) when compared to no radiation exposure. The results of flap failure were not significantly different between both groups (P = 0.3820). CONCLUSIONS: Minor complications and reoperation in the early postoperative period were not influenced by radiation exposure. The complications of radiation tend to be protracted and associated with additional operation later than 1 week after the initial surgery. It was thought that shortening of the duration of treatment was successful when we needed to perform early additional operations.

Sturge-Weber syndrome with cemento-ossifying fibroma in the maxilla and giant odontoma in the mandible: A case report.

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome with vascular lesions of the cerebral meninges, port wine spots on the face, and glaucoma of the eyes; it is a congenital, non-genetic disease whose etiology and mechanisms are unknown. In this report, we describe a rare case of SWS with unilateral large odontogenic tumors in the maxilla and mandible. The histopathological diagnosis of the maxillary bone lesion on biopsy was juvenile psammomatoid ossifying fibroma, which is considered a type of ossifying fibroma of craniofacial bone origin. However, the final pathological diagnosis of the excision was cemento-ossifying fibroma derived from periodontal ligament cells, and we discuss the histopathology in detail. In addition, the mandibular lesion was one of the largest odontomas reported to date. Furthermore, in this case, we suggest the possibility that the maxillary and mandibular bone lesions are not separate lesions, but a series of lesions related to SWS.

Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma.

Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro-tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph-circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC.

Toluene Exposure Leads to a Change in Expression Patterns of ß Defensins in the Mouse Tracheal Epithelium.

Defensins are generally implicated in the quick resistance of epithelial surfaces to microbials; however, recent reports have indicated that defensins also have unknown purposes in relation to noninfectious diseases. In this study, the localization patterns of anti-microbial peptides, ß defensins (BDs), in the tracheal epithelium of male C3H mice under exposure to toluene were analyzed by immunohistochemistry. Mice were exposed one to ten times to toluene for 30 min by nose-only inhalation. Expression of BDs was revealed by immunohistochemistry in serial sections of trachea after the final exposure. Expression of BD-1 was usually observed at almost the same levels in all exposure groups, and expression of BD-2 was observed in the control group; however, the signals for BD-2 decreased gradually with frequency of exposure. In the group exposed ten times, expression of BD-2 decreased to far lower than that of the control group. No expression of BD-3 was detected in any groups. Interestingly, expression of BD-4 increased to the maximum in the group exposed four times and decreased to a level lower than that of the control in the group exposed ten times. The results of the present study indicated that toluene gas might change the expression pattern of BDs in the tracheal epithelial cells. The oscillation of expression of BD-4 was quite characteristic and might contribute to morphological damage in on the epithelial cells.

Bone quality and quantity of the anterior maxillary trabecular bone in dental implant sites.

OBJECTIVES: The aim of this study was to investigate the characteristics of implant sites on the edentulous alveolar ridge in the anterior maxilla. We studied the bone quantity and quality of implant sites at the anterior maxilla using CT images for the 33 implant sites on patients who underwent dental implant therapy in our Department since 2006. MATERIALS AND METHODS: Computed tomography (CT) images of 33 patients (20 women: 13 men) encompassing 33 implant sites were chosen and examined. The recipient sites for implant placement were determined based on CT data using an implant planning software (Simplant 11.0). The mean bone density values in Hounsfield unit (HU) were recorded using Simplant for both the simulated implant areas and the trabecular bone width. We classified the edentulous alveolar ridge and bone quality according to a classification based on Lekholm and Zarb (1985). RESULTS: Incisors had higher bone densities than canines. Women had lower bone densities than men. Canines displayed greater trabecular bone density and alveolar bone widths than incisors. No maxillary sites were judged to have a bone quality of 1 in this group. Quality 3 accounted for 69.7% of the total samples. CONCLUSIONS: An assessment of bone quality in the anterior alveolar ridge may well reflect age-related systemic pathological conditions and should be used in dental implant treatment planning to avoid associated risk factors.

Epidemiological Correlations Between Head and Neck Cancer and Hepatitis B Core Antibody Positivity.

BACKGROUND/AIM: Hepatitis B core (HBc) antibody positivity indicates a history of hepatitis B virus (HBV) infection and latent infection. PATIENTS AND METHODS: We conducted a retrospective case-control study of 512 and 495 head and neck cancer (HNC) and non-HNC patients treated at the Okayama University Hospital, Head and Neck Cancer Center from 2008-2017. Demographic data and risk factors that might affect HNC diagnosis were analyzed to assess their effects. RESULTS: Cancer diagnosis was found to correlate with HBc antibody positivity [odds ratio (OR)=1.50, 95% confidence interval (CI)=1.09-2.08], smoking (OR=3.03, 95%CI=2.16-4.25), and a previous history of cancer (OR=4.12, 95%CI=2.79-6.09). The HBs antigen positivity rate in both groups was very close to that observed in the general Japanese population. The HBc antibody positivity rate was very high only in the HNC group. CONCLUSION: HBc antibody positivity and HNC are epidemiologically correlated.

Localization of antimicrobial peptides human beta-defensins in minor salivary glands with Sjögren's syndrome.

Sjögren's syndrome is a common systemic autoimmune disease associated with inflammatory cells that infiltrate exocrine glands. The antimicrobial peptides human beta-defensin-1, human beta-defensin-2, and human beta-defensin-3 are expressed in various human epithelial cells and in normal salivary glands. Antimicrobial peptides provide local protection against infection and participate in inflammatory responses. Because of the presence of inflammation, we hypothesized that human beta-defensin expression in minor salivary glands may be increased in subjects with Sjögren's syndrome. However, the expression of human beta-defensins 1 and 2 was decreased in salivary glands affected by Sjögren's syndrome in comparison with the human beta-defensin expression patterns in salivary glands from normal subjects. In addition, the reduction in expression of human beta-defensin-2 was greater than the reduction in expression of human beta-defensin-1. The aforementioned result suggests that the reduction in expression of human beta-defensin-2 may occur earlier than the reduction in expression of human beta-defensin-1, which may lead to a greater decrease in human beta-defensin-2 than in human beta-defensin-1 during disease progression.

Relationship Between Renal Dysfunction and Oral Mucositis in Patients Undergoing Concurrent Chemoradiotherapy for Pharyngeal Cancer: A Retrospective Cohort Study.

BACKGROUND/AIM: The aim of this retrospective cohort study was to investigate the association between renal dysfunction (RD) and the development of oral mucositis (OM) in patients undergoing concurrent chemoradiotherapy (CCRT) for pharyngeal cancer including radiation to the oral cavity. PATIENTS AND METHODS: Of 130 patients diagnosed as having pharyngeal cancer who received CCRT at the Okayama University Hospital Head and Neck Cancer Center, 44 were finally selected. RESULTS: During the observation period, 24 (54.5%) patients experienced severe OM (grade 3). The Cox proportional hazards regression model demonstrated that RD (hazard ratio(HR)=2.45, 95% confidence interval(CI)=1.067-6.116, p=0.035) and nasopharynx/oropharynx as center of the irradiated area (HR=2.56, 95% CI=1.072-5.604, p=0.034) were significantly associated with the incidence of severe OM (grade 3). CONCLUSION: In patients with pharyngeal cancer treated with CCRT including radiation to the oral cavity, RD at baseline can be a risk factor for developing severe OM.

Histological comparison of bone induced from autogenously grafted periosteum with bone induced from autogenously grafted bone marrow in the rat calvarial defect model.

Both periosteum and bone marrow have the potential to induce heterotopic bone when grafted. Whether the process of bone formation is controlled by the recipient environment where the donor graft is placed or by factors from the donor site is not well documented. The purpose of this study was to examine the histology of new bone induced by either autogenously grafted periosteum or autogenously grafted bone marrow using the rat calvarial defect model in Sprague-Dawley rats. Grafts of either bone marrow or periosteum obtained from tibias were placed in calvarial defects with beta-tricalcium phosphate. Ten days after grafting, active cell proliferation was observed in the defects of both types of grafts. After 20 days, cancellous bone formation was observed in the defects with bone marrow grafts, and intramembranous bone formation was observed in the defects with periosteal grafts. After 30 days, bone marrow grafts had developed bone with a bone marrow-like structure, and the periosteal grafts had produced cortical bone structure in the defects. The findings suggest that the type of bone formation is determined by characteristics of the donor site.

High concentration of beta-defensin-2 in oral squamous cell carcinoma.

We have previously reported the presence of human beta-defensin-2 (HBD-2), a peptide with antimicrobial and cytotoxic properties, in oral squamous cell carcinomas. The aim of the present study was to measure the concentration of HBD-2 in abnormal tissues such as oral squamous cell carcinomas. HBD-2 was extracted from tissue samples in the presence of retinoic acid and subjected to reversed-phase HPLC. The fraction representing peak 17 (P17) was obtained by elution using a linear gradient of acetonitrile. Amino acid sequencing and homology studies were subsequently performed, and the molecular weight of P17 was calculated to be 432702 daltons. This molecular weight was consistent with HBD-2. The concentration of HBD-2 in the oral squamous cell carcinoma samples was 3.85+/-1.87 microg/mg which was much higher than in normal oral epithelium (0.04+/-0.02 microg/mg).

Different expression patterns of beta-defensins in human squamous cell carcinomas.

The expression of human beta-defensin genes in oral squamous cell carcinomas(SCCs) was demonstrated by in situ hybridization. The expression of HBD-2 was observed not only in the inflamed lesions with bacterial infection but also in the non-inflamed carcinomas themselves (evident in 15 out of 20 carcinomas). However, HBD-3 expression was found in only 4 out of 20 SCCs. In the normal oral epithelia, the expression of HBD-2 and HBD-3 was only detected in the areas adjacent to the SCCs. These results suggest that HBD-2 might play a role in SCCs, which is different from the native defensive role of these proteins. HBD-2 may lead to the death of normal keratinocytes adjacent to the SCCs, which might, in turn, indirectly assist in the multiplication of tumor cells.

Mortality of human epidermal keratinocytes in co-culture with oral squamous cell carcinoma cells.

Normal human epidermal keratinocytes (NHEK) died after 5 days of co-culture with an oral carcinoma cell line (HSC-4). However, the HSC-4 cells did not change in either mitotic character or shape. We analyzed the changes in the mitotic activity and DNA synthetic activity of NHEK in co-culture with the HSC-4 cells. The mitotic index of the NHEK decreased gradually with the presence of human beta-defensin-2 (HBD-2) in the media. However, the mitotic index (MI) of the HSC-4 cells did not change. The shape of the NHEK cells did not change during co-culture. The time changes of the labeling index (LI) measured by BrdU incorporation, and the LI decreased in neither NHEK nor in HSC-4 cells in the presence of HBD-2. Moreover, in co-culture with an anti-HBD-2 antibody, the MI of both NHEK and HSC-4 cells did not change. These results indicate that HBD-2 might not lead to apoptosis or necrosis, but rather to cellular reproductive death in NHEK cells. However, HSC-4 cells might be more tolerant of HBD-2, so that HBD-2 does not cause cellular reproductive death. HBD-2 does not diminish the DNA synthesis rate but decreases the mitotic activity in NHEK cells in vitro. HBD-2 diminishes neither the DNA synthesis rate nor the mitotic activity in HSC-4 cells.

Expression pattern of cisplatin-induced metallothionein isoforms in squamous cell carcinoma.

Cisplatin (CDDP) is a useful drug for the treatment of malignant solid tumors of the head and neck. Because CDDP includes the heavy metal platinum as a component, it is thought metallothionein (MT) may be involved in CDDP-resistance. However, functional differences between the four MT isoforms (MT-I, II, III and IV) remain unclear. The aim of this study was to investigate the relationship between MT isoform expression and CDDP-resistance. Two human tongue squamous cell carcinoma cell lines not exposed to anticancer chemotherapy were studied. The cell lines were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) analysis before and after CDDP-treatment. Both cell lines expressed MT-I/II and MT-IV isoforms but not the MT-III isoform. Following CDDP treatment, MT-I/II mRNA levels were induced only in the CDDP-resistant cell line. Our results showed that expression of the MT I/II isoform was induced by CDDP treatment, and may play an important role in CDDP-resistance in squamous cell carcinoma of the human tongue.

Immunohistochemical observations of cellular differentiation and proliferation in endochondral bone formation from grafted periosteum: expression and localization of BMP-2 and -4 in the grafted periosteum.

PURPOSE: To clarify the involvement of bone morphogenetic proteins (BMPs) in the proliferation and differentiation of osteo/chondrogenic cells during the process of bone formation from grafted periosteum. MATERIAL AND METHODS: Tibial periosteum of young Japanese white rabbits was grafted into suprahyoid muscles and removed after 7, 9, 14 or 21 days. BMP-2, -4, proliferative cell nucleus antigen (PCNA) immunoreaction and Alcian blue staining in grafted periosteum was then sought microscopically. RESULTS: PCNA positive cells in the grafted periosteum expressed BMP-2 at 7 days. These cells differentiated into chondroblasts that expressed BMP-2 and Alcian blue at 9 days. After 14 days, cartilage formation was seen, and BMP-2 and -4 expressions were observed in mature and hypertrophic chondrocytes. Endochondral ossification was observed at 21 days and osteoblasts showed both BMP-2 and -4 expression. CONCLUSION: Both BMP-2 and -4 appear to play regulatory roles in the process of endochondral ossification from grafted periosteum, due to their involvement in the proliferation and differentiation into chondrogenic and osteogenic cells.

Pathology of the temporomandibular joint of patients with rheumatoid arthritis--case reports of secondary amyloidosis and macrophage populations.

INTRODUCTION: The pathogenetic features of rheumatoid arthritis of the temporomandibular joint (TMJ) are not well defined. In this paper the histological features of TMJs affected by rheumatoid arthritis, and the detection of secondary amyloidosis and macrophage populations in the TMJs of two patients with progressive rheumatoid arthritis are described. METHODS: In two patients (64-year-old man and 61-year-old woman) with rheumatoid arthritis total TMJ replacement were performed. The surgical specimens were studied histologically. RESULTS: It was found that the articular cartilage had been completely replaced by proliferating fibrous tissue. Congo red staining and polarizing microscopy revealed amyloid deposition in the connective tissue of the joint space. Immunohistochemical staining showed CD 68 positive macrophages around the amyloid deposition in the proliferating soft tissue. CONCLUSION: TMJ involvement in rheumatoid arthritis followed the same destructive pathway as in other joints. Amyloid deposition and macrophage populations were detected in two TMJs affected by rheumatoid arthritis.