Radiotherapy Plus Cetuximab for Squamous Cell Carcinoma of the Oral Cavity: A Multicenter Retrospective Study of 79 Patients in Japan.

There are a few reports that focus on radiotherapy (RT) and cetuximab (CET) therapy exclusively for oral cancer. This retrospective study aimed to investigate the efficacy and safety of RT and CET therapy for locally advanced (LA) or recurrent/metastatic (R/M) oral squamous cell carcinoma (OSCC). Seventy-nine patients from 13 hospitals who underwent RT and CET therapy for LA or R/M OSCC between January 2013 and May 2015 were enrolled in the study. Response, overall survival (OS), disease-specific survival (DSS), and adverse events were investigated. The completion rate was 62/79 (78.5%). The response rates in patients with LA and R/M OSCC were 69% and 37.8%, respectively. When only completed cases were examined, the response rates were 72.2% and 62.9%, respectively. The 1- and 2-year OS were 51.5% and 27.8%, respectively (median, 14 months), for patients with LA OSCC, and 41.5% and 11.9% (median, 10 months) for patients with R/M OSCC. The 1- and 2-year DSS were 61.8% and 33.4%, respectively (median, 17 months), for patients with LA OSCC, and 76.6% and 20.4% (median, 12 months) for patients with R/M OSCC. The most common adverse event was oral mucositis (60.8%), followed by dermatitis, acneiform rash, and paronychia. The completion rate was 85.7% in LA patients and 70.3% in R/M patients. The most common reason for noncompletion was an inadequate radiation dose due to worsening general conditions in R/M patients. Although the standard treatment for LA or R/M oral cancer is concomitant RT with high-dose cisplatin (CCRT) and the efficacy of RT and CET therapy for oral cancer is not considered to be as high as that for other head and neck cancers, it was thought that RT and CET therapy could be possible treatments for patients who cannot use high-dose cisplatin.

Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC.

OBJECTIVES: The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined. PATIENTS AND METHODS: The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis. RESULTS: ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor. CONCLUSIONS: These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients. CLINICAL RELEVANCE: This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.

Platelet-rich fibrin has a healing effect on chemotherapy-induced mucositis in hamsters.

OBJECTIVE: The aim of this study was to evaluate the healing effect of topically applied platelet-rich fibrin (PRF) on experimental oral mucositis induced by chemotherapy in hamsters. STUDY DESIGN: Oral mucositis was induced in 93 Syrian golden hamsters by an intraperitoneal injection of 5-fluorouracil, which was followed by light scratching of the cheek pouch. The hamsters were randomly divided into a PRF group, a fibrin group, and an untreated control group. The recovery stage of oral mucositis was evaluated through daily weighing, measurements of the ulcer area, histopathologic analysis, and a myeloperoxidase activity assay. RESULTS: The PRF group exhibited significant improvements in the size and histologic features of the ulcer and in the myeloperoxidase activity compared with the control group (P < .05). CONCLUSIONS: The current findings suggest the consideration for future clinical trials in humans.

Bone regeneration with self-assembling peptide nanofiber scaffolds in tissue engineering for osseointegration of dental implants.

The aim of this study was to evaluate the correlation between the osseointegration of dental implants and tissue-engineered bone using a nanofiber scaffold, PuraMatrix (PM). The first molar and all premolars in the mandibular regions of dogs were extracted, and three bone defects were prepared with a trephine bur on both sides of the mandible after 4 weeks. The experimental groups were as follows: (1) PM, (2) PM and dog mesenchymal stem cells (dMSCs), (3) PM, dMSCs, and platelet-rich plasma, and (4) control (defect only). Implants were placed in the prepared areas 8 weeks later and were assessed by histologic and histomorphometric analyses (bone-to-implant contact [BIC]). The BICs for groups 1, 2, 3, and 4 were 40.77%, 50.35%, 55.64%, and 30.57%, respectively. The findings indicate that PM may be useful as a scaffold for bone regeneration around dental implants.

Self-assembling peptide nanofiber scaffolds, platelet-rich plasma, and mesenchymal stem cells for injectable bone regeneration with tissue engineering.

The purpose of this study was to investigate a capability of PuraMatrix (PM), which is a self-assembling peptide nanomaterial, as a scaffold for bone regeneration in combination with dog mesenchymal stem cells (dMSCs) and/or platelet-rich plasma (PRP) using tissue engineering and regenerative technology. Initially, teeth were extracted from an adult hybrid dog's mandible region. After 4 weeks, bone defects were prepared on both sides of the mandible with a trephine bar. The following graft materials were implanted into these defects: (1) control (defect only), (2) PM, (3) PM/PRP, (4) PM/dMSCs, and (5) PM/dMSCs/PRP. From scanning electron microscope images, PM had a three-dimensional nanostructure, and dMSCs attached on the surface of PM. At 2, 4, and 8 weeks after implantation, each sample was collected from the graft area with a trephine bar and assessed by histologic and histomorphometric analyses. It was observed that the bone regenerated by PM/dMSCs/PRP was of excellent quality, and mature bone had been formed. Histometrically, at 8 weeks, newly formed bone areas comprised 12.39 +/- 1.29% (control), 25.28 +/- 3.92% (PM), 27.72 +/- 3.15% (PM/PRP), 50.07 +/- 3.97% (PM/dMSCs), and 58.43 +/- 5.06% (PM/dMSCs/PRP). The PM/dMSCs and PM/dMSCs/PRP groups showed a significant increase at all weeks compared with the control, PM, or PM/PRP (P < 0.05 at 2, 4, and 8 weeks, analysis of variance). These results showed that MSCs might keep their own potential and promote new bone regeneration in the three-dimensional structure by PM scaffolds. Taken together, it is suggested that PM might be useful as a scaffold of bone regeneration in cell therapy, and these results might lead to an effective treatment method for bone defects.

Injectable soft-tissue augmentation by tissue engineering and regenerative medicine with human mesenchymal stromal cells, platelet-rich plasma and hyaluronic acid scaffolds.

BACKGROUND AIMS: The aim of this study was to evaluate the possibility of soft-tissue augmentation adopting tissue engineering and regenerative medicine (TERM) technology for a longer duration of injected implants. METHODS: TERM is the combination and re-organization of three types of injection materials to regenerate organs and tissues: (i) living cells, including cultured human mesenchymal stromal cells (hMSCs) and human fibroblasts (hFibro); (ii) scaffolds of hyaluronic acid (HA); and (iii) growth factors of platelet-rich plasma (PRP). The experimental combinations were as follows: HA, HA/hFibro, HA/hMSCs, HA/PRP, HA/PRP/hFibro and HA/PRP/hMSCs. These were injected intradermally into immunodeficient rats and evaluated by histologic analysis, percentage of original volume and maintenance volume. RESULTS: The percentage of original volume values at 14 days were 0.02 +/- 0.01% (HA), 0.20 +/- 0.03% (HA/hFibro), 0.50 +/- 0.02% (HA/hMSCs), 11.66 +/- 1.81% (HA/PRP), 24.36 +/- 8.97% (HA/PRP/hFibro) and 28.04 +/- 4.11% (HA/PRP/hMSCs), respectively. There were significant differences between groups with and without PRP. Regarding maintenance volume values, HA/PRP, HA/PRP/hFibro and HA/PRP/hMSCs from 7 to 14 days were also higher, at 46.25 +/- 1.21%, 78.39 +/- 2.90% and 88.81 +/- 5.97%, respectively. HA/PRP/hMSCs groups maintained the shape and dimensions of the injected implant, indicating that the injected cells produced type I collagen. CONCLUSIONS: The findings suggest that a soft tissue-engineered procedure with MSCs may be useful for longer lasting soft-tissue augmentation.

Injectable tissue-engineered bone using autogenous bone marrow-derived stromal cells for maxillary sinus augmentation: clinical application report from a 2-6-year follow-up.

This clinical study used injectable tissue-engineered bone, along with bone marrow-derived stromal cells (BMDSCs) and platelet-rich plasma (PRP), to conduct maxillary sinus floor augmentation by the simultaneous placement of bone graft and dental implants and to examine the state of regenerated bone after functional loading in 16 sinus augmentations in 12 patients whose alveolar crestal bone height was 2-10 mm. We used PRP as an autologous scaffold-which provides signal molecules-with in vitro expanded BMDSCs to enhance osteogenesis. All 41 dental implants prepared with the materials were clinically stable after second-stage surgery. The height of mineralized tissue at 2 years showed the mean increases of 8.8 +/- 1.6 mm compared to preoperative values, and no adverse effects and remarkable bone absorption were seen in the 2-6-year follow-up time. Although these results are preliminary, injectable tissue-engineered bone would stably predict the success of bone formation and dental implants, reduce patient burden, and provide minimally invasive cell therapy for patients.