Teriparatide therapy for severe, refractory osteoradionecrosis of the jaw.

Although osteoradionecrosis (ORN) is a serious complication of craniofacial radiotherapy, the current management methods remain suboptimal. Teriparatide (TPTD), a recombinant human parathyroid hormone (1-34), has shown beneficial effects on osseous regeneration in medication-related osteonecrosis of the jaw or periodontitis. However, TPTD therapy in irradiated bones has not been indicated yet because of the theoretical risk of osteosarcoma seen in rat models. Hence, we first report here two patients with tongue cancer with late-emerging ORN who were successfully treated with TPTD for 4-6 months with serum calcium and vitamin D supplementation. In contrast to the usual progress of ORN, the bone defect regenerated well and bone turnover markers including serum C-terminal telopeptide of type 1 collagen and osteocalcin were restored with TPTD therapy. Our experience might suggest that TPTD therapy with careful monitoring can provide an effective treatment option for patients with ORN in select refractory cases, with the benefits outweighing the potential risks.

Effects of locally administered rhBMP-2 and bisphosphonate on bone regeneration in the rat fibula.

OBJECTIVE: To evaluate the ability of xenogenic bone and absorbable collagen sponge to function as an rhBMP-2 carrier and the osteoinductivity of bisphosphonate by comparison with recombinant human bone morphogenetic protein-2 (rhBMP-2). MATERIALS AND METHODS: Thirty-two Sprague-Dawley male rats were divided into four groups. Segmental ostectomy of both fibulae was performed, and the defect area was then treated with Rapiderm Pad (absorbable collagen sponge; COL_BMP) or CollaOss (xenogenic bone; XENO_BMP) with application of rhBMP-2. Alternatively, both fibulae were grafted with xenogenic bone with different bisphosphonate concentrations (XENO_Low BP, XENO_High BP). After 4 or 8 weeks, animals were sacrificed, and radiographic, histological, histomorphometric, and immunohistochemical analyses were performed. RESULTS: Recombinant human bone morphogenetic protein-2 promoted bone formation, regardless of the carrier, and exhibited continuity between the graft material and defect area. Moreover, the results showed that higher concentrations of bisphosphonate were associated with greater bone formation than lower concentrations of bisphosphonate. CONCLUSION: Absorbable collagen sponges with rhBMP-2 were advantageous in that there was no remaining graft material and that the bone was remodeled to resemble the existing fibula. The local application of bisphosphonate promoted new bone formation, particularly when used at high concentrations. High-concentration bisphosphonate induced new bone formation comparable to rhBMP-2 with lesser remaining bone material.

A combined prognostic factor for improved risk stratification of patients with oral cancer.

PURPOSE: We aimed to identify a combined prognostic factor for predicting better performance in risk stratification. MATERIALS AND METHODS: We reviewed the clinical and pathological variables of 316 patients with oral squamous cell carcinoma (OSCC) who underwent surgery. To identify a combined predictor, principal component analysis (PCA) was performed. RESULTS: Univariate analysis showed that the independent prognostic variables for overall survival (OS) were pathologic T stage (T1 vs T4, HR = 1.99, 95% CI: = 1.083-3.675, P = 0.026) and pathologic N stage (N0 vs N2, HR=1.90, 95% CI: = 1.17-3.08, P = 0.008). In the multivariate analysis, only pathologic T stage was significant (P = 0.006 and P = 0.007); however, the multivariate model was not significant (P = 0.191). The multivariate model became significant by including lymph node ratio (LNR) instead of pathologic N stage (P = 0.0025 in numeric LNR, P = 0.0007 in categorized LNR). Also, the performance of prediction model was improved by a combined prognostic factor (P = 0.0002). CONCLUSIONS: The newly identified combined prognostic factor included resection margin, differentiation, and LNR, and they were insignificant factors independently except for LNR. This combined prognostic factor showed a good performance although it did not include molecular markers; therefore, it may be used conveniently for risk stratification of patients with OSCC by combining only clinical information.

Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw.

UNLABELLED: The administration of teriparatide (TPTD) in conjunction with periodontal care could provide faster and more favorable clinical outcomes in previously refractory bisphosphonate-related osteonecrosis of the jaws (BRONJ) cases compared to conventional dental care, combination of surgery and antimicrobial treatment. We also found that underlying vitamin D levels might influence the response to TPTD treatment. INTRODUCTION: Treatment of BRONJ is quite challenging and there are no standard treatment modalities. In this retrospective, longitudinal study, we examined whether additional TPTD administration could be beneficial for the resolution of BRONJ lesions compared to conservative management, such as antimicrobial treatment with or without surgery, and also studied the factors influencing the response to TPTD. METHODS: Twenty-four cases of intractable BRONJ were included: 15 subjects were assigned to the TPTD group and the other 9 subjects, who refused TPTD administration, were assigned to the non-TPTD group. All subjects in both groups continued calcium and vitamin D supplementation and the TPTD group additionally received a daily subcutaneous injection of 20 µg TPTD for 6 months. RESULTS: While 60.0% of the non-TPTD group showed one stage of improvement in BRONJ, 40.0% of the group did not show any improvement in disease status. In the TPTD group, 62.5% of the treated subjects showed one stage of improvement and the other 37.5% demonstrated a marked improvement, including two stages of improvement or complete healing, and there was not a single case that did not improve. The clinical improvement of BRONJ was statistically better in the TPTD group after the 6-month treatment (p < 0.05). Moreover, patients with higher baseline serum 25(OH)D levels showed better clinical therapeutic outcomes with TPTD. CONCLUSIONS: We observed the beneficial effects of TPTD on BRONJ, and subjects with optimal serum vitamin D concentrations seemed to reap the maximum therapeutic effects of TPTD. A prospective, randomized, controlled trial should be needed to further evaluate the therapeutic efficacy of TPTD in the resolution of BRONJ.

Socioeconomic disparities of periodontitis in Koreans based on the KNHANES IV.

OBJECTIVES: The aim of this study was to identify the socioeconomic factors associated with the prevalence of periodontitis in Koreans. METHODS: Cross-sectional data from 12 763 subjects, 15 years old and above, who underwent periodontal examinations were obtained from the Korean National Health and Nutrition Examination Survey IV (2007-209). Multivariate linear and logistic regression analyses were applied to estimate the association between socioeconomic indicators and prevalence of periodontitis. RESULTS: A significant association was found between increasing age and periodontitis. Participants with higher income were less likely to have periodontitis (aOR = 0.9 and 95% CI = 0.78-0.98, and aOR = 0.7 and 95% CI = 0.60-0.80 in the middle and highest quintiles of monthly household income, respectively). In addition, participants living in rural areas were less likely to have periodontitis (aOR = 0.9 and 95% CI = 0.81-0.99), and current smokers were more likely to have periodontitis (aOR = 1.7 and 95% CI = 1.49-1.89). The analysis of comorbidities revealed that individuals with diabetes mellitus (DM) were significantly more likely to have periodontitis (aOR = 1.4 and 95% CI = 1.18-1.68). CONCLUSIONS: In a rapidly increasing Korean population, the lower socioeconomic groups as well as individuals with DM were significantly more likely to present with periodontitis.

Prognostic factors and impact of bone invasion in T1/2 size (<4 cm) gingival squamous cell carcinoma.

The aim of this study was to characterize the clinicopathological features and prognostic factors of T1/2 size (<4 cm) gingival squamous cell carcinoma (SCC) and to verify the impact of bone invasion. This was a single-centre, retrospective cohort study involving 206 patients with gingival SCC (maxilla or mandible), treated between 2000 and 2020. The patients were divided into three subgroups based on tumour size and bone invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were 80.6% and 67.6%, respectively. Histological differentiation, advanced T stage, positive resection margin, bone invasion, and postoperative adjuvant therapy were associated with a poor prognosis (P < 0.05). Multivariate Cox analysis indicated that only histological differentiation (hazard ratio (HR) 2.68, P = 0.007) and bone invasion (HR 2.08, P = 0.036) were significantly associated with DFS. Bone invasion was observed in 145 (70.4%) patients, of whom 43 (20.9%) had a T1/2 size tumour. The subgroup with bone invasion and T1/2 size showed significantly worse OS and DFS when compared to the subgroup without bone invasion and similar or worse survival when compared to the subgroup with bone invasion and T3/T4 size. Histological differentiation and bone invasion were poor prognostic factors for gingival SCC, even in cases with small-sized tumours. For suspected bone invasion in small-sized tumours, an adequate bone margin is necessary and postoperative adjunctive therapy needs to be considered.

Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia.

UNLABELLED: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of bisphosphonate therapy. The incidence of BRONJ is known to be low among patients treated with oral bisphosphonates. We investigated the prevalence, demographics, clinical manifestations, and treatment outcome of 24 patients with oral BRONJ in Asian populations. INTRODUCTION: The long-term safety of oral bisphosphonates is clinically important considering the rare but potentially serious complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus the effect of reducing and preventing osteoporotic fracture. The incidence of BRONJ is known to be low among patients treated with oral bisphosphonates around the world. However, the prevalence in those taking oral bisphosphonates for osteoporosis in Asian populations is unknown. Moreover, a recent article, showing that the majority of reported patients who received alendronate were Asian American, raised concern about the prevalence of oral BRONJ in Asian populations. The objective of this study was to investigate the estimated prevalence, clinical characteristics, and treatment outcome of oral BRONJ in Asian populations. METHODS: From October 2005 to December 2008, a retrospective review of medical charts identified 24 patients receiving oral bisphosphonates diagnosed as BRONJ at the Department of Oral and Maxillofacial Surgery, Yonsei University Dental Hospital, Seoul, South Korea. RESULTS: The estimated prevalence of oral BRONJ was 0.05-0.07%. The average oral bisphosphonate treatment duration was 43.1 months (range, 5-120 months). Treatment with oral antibiotics and/or surgery including sequestrectomy or alveolectomy showed relatively favorable results. CONCLUSIONS: The prevalence of oral BRONJ in Korea is similar to that reported previously in Western populations. We suggest that recognition of BRONJ and appropriate management pre- and post-dental surgery might reduce the frequency of BRONJ among patients receiving oral bisphosphonates.

Endovenous laser ablation of the incompetent small saphenous vein with a 980-nm diode laser: our experience with 3 years follow-up.

PURPOSE: To demonstrate the long-term treatment outcomes of endovenous laser ablation (EVA) of incompetent small saphenous veins (SSV) with a 980-nm diode laser. MATERIALS AND METHODS: Eighty-four patients (96 limbs), with varicose veins and reflux in the SSV on duplex ultrasound examination, were treated with a 980-nm diode laser under ultrasound- or fluoroscopy-guidance. Patients were evaluated at 1 week and 1, 3, 6 months, 1 year and yearly thereafter. RESULTS: In the 96 limbs, the technical success rate was 100%. The SSV remained closed in 89 of 93 limbs (96%) after 1 month, all of 82 limbs after 6 months, 77 limbs after 1 year, 71 limbs after 2 years and 55 limbs after 3 years. In four limbs where recanalisation was observed, repeat EVA was done resulting in successful obliteration of the SSV. No major complication occurred however bruising (27%), tightness or pain (13%) and paraesthesia (4.2%) were observed. CONCLUSION: Endovenous laser ablation with a 980-nm laser wavelength is an easy and safe procedure in incompetent SSVs. After successful treatment, there is a very low rate of recanalisation of the SSV, which suggests that the procedure will provide lasting results.

Prognostic value of lymph node count from selective neck dissection in oral squamous cell carcinoma.

Unlike the levels of anatomical exploration, there is no consensus on the extent of lymph node dissection, or lymph node count (LNC), during selective neck dissection (SND). The aim of this study was to validate the prognostic impact of LNC on survival and to determine an optimal LNC cut-off value for SND. A retrospective investigation identified 78 patients with a diagnosis of oral squamous cell carcinoma (OSCC) who underwent SND (levels I-III or levels I-IV). LNC and clinicopathological variables were analyzed for any association with survival in Cox proportional hazards models. Based on the receiver operating characteristic curve, a cut-off value of 19 lymph nodes was found to predict overall survival (OS) (area under the curve 0.732, sensitivity 67.8%, specificity 75.0%; P=0.026) and disease-specific survival (DSS) (area under the curve 0.762, sensitivity 68.1%, specificity 77.8%; P=0.011). On Cox regression, LNC (≥19 vs. <19) was the only independent predictor of OS (hazard ratio 5.29, 95% confidence interval 1.39-20.05; P=0.014) and DSS (hazard ratio 6.76, 95% confidence interval 1.40-32.77; P=0.018). Similar results were obtained in the pathologically lymph node-negative subgroup (n=66). Based on the study findings, SND should include 19 or more lymph nodes for a survival benefit.

Spontaneous bone formation on the maxillary sinus floor in association with an extraction socket.

A case is reported of spontaneous bone formation on the maxillary sinus floor associated with the extraction socket of a maxillary impacted tooth. An impacted maxillary second premolar of a 20-year-old male had been pushed into the maxillary sinus during surgical extraction. The tooth was removed using the sinus elevation technique. After 5 months of healing, the space between the sinus floor and the socket was filled with new bone. Later, implant surgery was successfully carried out without any sinus augmentation. Osteogenic activity of sinus mucosa and the blood clot in the extraction socket beneath the elevated sinus would have been important factors in this spontaneous bone formation.

Mandibular invasion of lower gingival carcinoma in the molar region: its clinical implications on the surgical management.

The spread pattern of a tumour and its extent in the mandible are important in the management of gingival cancer. Sixteen patients with gingival squamous cell carcinoma (SCC) involving the mandible in the molar region were included in this study. Resection specimens of the mandibular bone and adjacent cancer were histologically analysed to identify the type and characteristics of invasion and were compared with the radiological features. Our results showed that the actual width of invasion was underestimated to a greater extent than the actual depth of invasion. For horizontal aspects, four dentate cases had horizontal intramedullary spread underneath intact mucosa or cortical bone extended from the main foci of tumour that infiltrated through the occlusal surface. For vertical aspects, nerve invasion took place in only one of 16 specimens, while five cases showed downward infiltration beyond the inferior alveolar canal without nerve involvement, so that the pattern of tumour spread was mostly transmedullary rather than perineural in previously non-irradiated cases. These cases with deep infiltration showed the infiltrative type of invasion in the dentate mandible. And when the tumour was related with previous dental extractions or curettage, it tended to be more extensive than what was predicted from an imaging point of view. These pathological and clinical features affecting the tumour spread should be considered in the management of gingival SCC in the molar region.

Regional thickness of parietal bone in Korean adults.

To clarify the clinical utility of the parietal bone graft in maxillofacial reconstruction, we performed an anatomical study by measuring the regional thickness of the parietal bone in 47 Korean adult dry skulls. Before sectioning of the calvaria, the appropriate anatomical landmarks were marked on each specimen. We measured the total thickness of the parietal bone, and the thickness of the outer and inner cortical plates at various points in each section of parietal bones using a digital caliper under the stereomicroscope. The total thickness of the parietal bone ranged from 5.04mm to 7.17mm, and there was no statistical difference in the total thickness of the parietal bone on the same points bilaterally. The parietal bone tended to be thicker toward the lambda point than at the coronal suture area. On the other hand, the outer plate of parietal bone was thickest at the point nearest to the coronal suture, and the inner plate proved thickest at the posteromedial area. In conclusion, this study showed that the better donor site of the parietal bone for maxillofacial reconstruction is located at its more posterior and medial area.

Topographical anatomy of the fibula and peroneal artery in Koreans.

Vascularized fibula flaps have many advantages in the restoration of the contour and function of the mandible. Potential disadvantages include, unreliable skin paddle and the limited volume of the fibula. This study was designed, to clarify the anatomy of the peroneal artery to the fibula and lateral leg skin, and to measure the dimensions of the fibula available for dental implant placement in Korean. Through the dissection of 63 legs of Korean cadavers, we demonstrated that in most cases the musculoperiosteal (mp) and septocutaneous (sc) branches of the peroneal artery were distributed at the middle and lower thirds of the fibula. There were double the number of mp perforators to the skin compared to sc branches. This indicates the inclusion of a generous > 1 cm cuff of Peroneous longus and flexor hallucis longus (FHL) in the distal and middle third of the fibula. The location of the nutrient foramen was just proximal to the midpoint. Thus, a 15-20 cm length of the fibula is available in Koreans and an 8 12 mm length of implant can be placed to the fibula, which provides sufficient bone to reconstruct a large mandibular defect.

Mandibular anatomy related to sagittal split ramus osteotomy in Koreans.

Sagittal split ramus osteotomy (SSRO) is one of the surgical techniques used to correct mandibular deformities. In order to prevent many surgical anatomical problems, we observed the anatomical structures related to SSRO. In dry mandibles of Koreans, lingular tips were located somewhat posteriorly and superiorly on the mandibular ramus. On the coronal sections of mandible, the mean cortical width of facial cortex was increased toward the ramus region while the lingual cortex was thinnest in the ramus region. On the same sections, all the fusion points of the buccal and lingual cortical plate were located above the mandibular lingula and beneath the mandibular notch. So, performing the SSRO on Koreans, medial horizontal osteotomy should be done through the superior aspect of the mandibular lingula. The cut line is extended 5-8 mm posterior to the mandibular lingula to preserve sufficient cortical width to strengthen the involved osseous segments and reduce possible surgical complications.

Solitary plasmacytoma of the mandible in a renal transplant recipient.

A solitary plasmacytoma occurring in the mandible of a 15-year-old Korean male 6 years after renal transplantation is reported. The tumour presented as a hyperplastic gingival overgrowth in the right madibular molar area. Histology and immunohistochemistry revealed plasmacytoma and monoclonality of the kappa chain and IgG. In situ hybridization for Epstein-Barr virus encoded RNA (EBER) showed positive signals in the tumour cells. The tumour regressed after reducing the immunosuppressive agents with concurrent radiotherapy. The patient remains in a stable condition with normal renal functions after 7 years without recurrence. This case confirms that Epstein-Barr virus associated B-lymphoproliferative disorders are still a major complication of immunosuppression.

Hyperdense enhancement of pancreatic adenocarcinoma on spiral CT: two case reports.

We are reporting two cases of pancreatic adenocarcinoma that showed dense contrast enhancement on the early phase spiral CT scan and isodensity on the delayed phase scan. Both lesions were located in the head portion of the pancreas, with diameters of 2 cm and 5 cm, respectively. Despite its extremely rare incidence, adenocarcinoma may be included in the differential diagnosis of enhanced pancreatic tumor on early-phase spiral CT scan.

Osteolytic mandible presenting as an initial manifestation of an adult acute lymphoblastic leukaemia.

A case of adult acute lymphoblastic leukaemia is reported. A 35-year-old male presented with an osteolytic lesion of the mandible. There was no definitive involvement in other craniofacial bones. A panoramic radiograph taken 4 months previously showed no bony involvement. A complete blood count showed a slightly decreased red blood cell count, but normal white blood cell count, white blood cell differential count and platelet count. Routine chemistry revealed hypercalcemia with an increased level of parathyroid hormone-related protein. Histopathological examination of bone marrow biopsy confirmed the diagnosis of acute lymphoblastic leukaemia.

Spinal cord injury subsequent to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

Transcatheter arterial chemoembolization is one of the most common treatment modalities for hepatocellular carcinoma. Transcatheter arterial chemoembolization is considered to be a relatively safe procedure, but transcatheter arterial chemoembolization is associated with a number of disastrous complications. Among the ischaemic complications caused by transcatheter arterial chemoembolization, spinal cord injury is very rare, but can occur via the intercostal or lumbar arteries. We report two cases of extremely rare spinal cord injuries after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. The patients had sensory loss below the T9 or T10 dermatomes and paraparesis or paraplegia within 6-8h after transcatheter arterial chemoembolization. One patient sustained paraplegia until death 2 months after transcatheter arterial chemoembolization and the other patient recovered almost completely 2 months after transcatheter arterial chemoembolization.

[Functional scintigraphy of salivary glands of the head during telecobalt radiotherapy]. / Funktionsszintigraphie der Kopfspeicheldrüsen im Verlauf einer Telekobalttherapie.

In order to find out radiogenic lesions to the large salivary glands of the head, the function of parotid and submandibular glands was examined by scintigraphy with 99m-Tc Pertechnetate before, during, and five to eight months after a telecobalt therapy for malignomas of the neck. It was shown that the parotid glands did not function at all immediately after an irradiation with 60 Gy. Five to eight months later, a recovery of about 50% of the secretory function was registered. The function of the submandibular glands was reduced to about 60% of their normal secretion after 30 and 60 Gy. This corresponds to the modification of xerostomia reported by the patients some time after an irradiation of the salivary glands.

Cloning and sequence analysis of another Shiga-like toxin IIe variant gene (slt-IIera) from an Escherichia coli R107 strain isolated from rabbit.

An Escherichia coli R107 strain (O26 serotype) producing a Shiga-like toxin IIe variant (SLT-IIera) was isolated from the mesenteric lymph node of a freshly dead rabbit carcass. The entire structural gene for this SLT-IIera was cloned from chromosomal DNA by PCR using primers based on previously published slt-IIe sequences. Nucleotide sequence analysis indicated that the slt-IIera gene was very similar to slt-IIe (formerly called slt-IIv) from E. coli strains S1191 and 412; five and one nucleotide changes were detected in A and B subunits, respectively, which resulted in changes in amino acid sequences of the corresponding subunits by three and one residues. Recombinant SLT-IIera and SLT-IIe produced using an E. coli host-vector system showed similar cytotoxicity, suggesting that the variations in the structural gene of SLT-IIera have no significant effect on cytotoxic level.