Three-dimensional analysis of decompression efficacy and influencing factors in the maxillofacial cystic lesions: a retrospective study.

Objectives: To evaluate the effectiveness of decompression and various parameters that may affect volume change in cystic lesions. Patients and. Methods: This retrospective study included patients who visited the Department of Oral and Maxillofacial Surgery at Ewha Womans University Medical Center between 2012 and 2022 for decompression of cystic lesions of the jaw. To measure volume changes, pre- and post-decompression cone-beam computed tomography was performed and reconstructed in three dimensions using Mimics 25.0 software (Materialise NV). A comparative analysis was performed based on sex, age, initial cyst volume, location, degree of cortical layer expansion, and pathologic diagnosis using the Mann-Whitney U and Kruskal-Wallis tests. Results: In all 20 cases, the duration of decompression was 7.84±3.35 months, and all patients successfully completed the decompression period without any complications. Significant differences were observed in the reduction rate and shrinkage speed based on the degree of cortical layer expansion. However, only the shrinkage speed (not the reduction rate) showed a significant difference with respect to the initial cyst volume. Significant differences were not observed based on sex, age, location, or pathologic diagnosis. Conclusion: Although the present study involved a small number of cases, the effectiveness of decompression was confirmed. In particular, 3D analysis overcame the shortcomings of previous studies of decompression and allowed earlier resection. Further studies with more patients are required to provide a rationale for these results and identify factors that influence decompression.

Prediction of medication-related osteonecrosis of the jaws using machine learning methods from estrogen receptor 1 polymorphisms and clinical information.

Objective: The purpose of this study was to evaluate the effect of estrogen receptor 1 (ESR1) polymorphisms on the development of medication-related osteonecrosis of the jaws (MRONJ) in women with osteoporosis. Methods: A total of 125 patients taking bisphosphonates was evaluated the relationship between MRONJ occurrence and single nucleotide polymorphisms (SNPs) of ESR1. Clinical information was collected, including current age, treatment duration, and comorbidity. Univariate and Multivariable regression analyzes were performed to evaluate the independent predictive factors for MRONJ occurrence. Predictive models were constructed using machine learning methods such as Lasso regression, Random forest (RF), and Support vector machine (SVM). The area under the receiver-operating curve (AUROC) was used to evaluate the performance of a binary classifier. Result: Two SNPs of ESR1 (rs4870056 and rs78177662) were significantly associated with MRONJ development. Patients with variant allele (A) of rs4870056 showed 2.45 times (95% CI, 1.03-5.87) the odds of MRONJ occurrence compared to those with wild-type homozygote (GG) after adjusting covariates. Additionally, carriers with variant allele (T) of rs78177662 had higher odds than those with wild-type homozygote (CC) (adjusted odds ratio (aOR), 2.64, 95% CI, 1.00-6.94). Among demographic variables, age ≥ 72 years (aOR, 3.98, 95% CI, 1.60-9.87) and bisphosphonate exposure ≥48 months (aOR, 3.16, 95% CI, 1.26-7.93) were also significant risk factors for MRONJ occurrence. AUROC values of machine learning methods ranged between 0.756-0.806 in the study. Conclusion: Our study showed that the MRONJ occurrence was associated with ESR1 polymorphisms in osteoporotic women.

Six-month stability following extensive alveolar bone augmentation by sausage technique.

BACKGROUND: Resorption of alveolar bone is a common sequela of tooth loss and presents a clinical problem, especially in the esthetic zone. When ridge resorption occurs, adequate bone augmentation is essential to obtain satisfactory esthetic results. The purpose of this study was to determine the increase and retention rate of bone height or width in patients who received extensive bone augmentation and to analyze factors affecting its prognosis and stability. METHODS: This study was performed on patients who received extensive bone augmentation by sausage technique at the Department of Oral and Maxillofacial Surgery at Ewha Womans University Mok-dong Hospital from January 1, 2018, to February 28, 2022. CBCT images were taken before and 6 months after surgery to compare the amount of increase in bone height or width at the graft site. They were measured using reliable points such as adjacent implants or cephalometric landmarks, inferior alveolar nerve canals as reference points. RESULTS: A total of 8 patients underwent extensive bone grafting during the given period (mean age was 53.75 years, 2 males and 6 females). Four patients received horizontal augmentation, and 4 received vertical augmentation. When divided by surgical site, 4 patients are in maxilla and 4 in mandible. The average amount of increase in bone width or bone height was 5.38 mm, and the retention rate was about 79.9% after 6 months. The retention rate of horizontal augmentation was 88.8%, which was higher than that of vertical augmentation, which was 74.5%. The maxillary area accounted for 92.2%, and the amount of bone resorption was lower than that of the mandibular area, which was 72.6%. The average stitch out period was about 2.4 weeks, and postoperative dehiscence was observed about 37.5% of the total, more frequently in the mandible (50.0%) than in the maxilla (25.0%). CONCLUSION: In conclusion, extensive bone augmentation achieved significant horizontal or vertical bone height or width increase, and the retention rate after 6 months was also high. In addition, surgery in the maxillary region showed a more successful bone augmentation than in the mandible, with a higher maintenance rate and fewer cases of dehiscence.

Narrow Alveolar Ridge Management with Modified Ridge Splitting Technique: A Report of 3 Cases.

Purpose: In this study, we report the usefulness of implant placement with modified ridge splitting technique from three cases of patients with narrow alveolar ridge. Materials and Methods: Three patients were those who visited the Department of Oral and Maxillofacial Surgery of Ewha Medical Center for consultation regarding implant placement. Through clinical and radiographic evaluation, narrowed alveolar ridge after tooth loss was confirmed in all three patients. For them, it was necessary to use the modified ridge split technique with bone augmentation for the implant to be well placed with enough bone width. Results: In all cases, sufficient bone width was confirmed for implant placement, and bone volume was well maintained after prosthetic restoration without any complications. Initial width of alveolar bone was 4.9 mm on average and was well maintained at an average of 7.6 mm at 1-year follow-up after implant installation. Conclusion: Although the number of subjects in this case report was small and was done by only one surgeon, we suggest that modified ridge splitting technique might be a useful surgical method to enhance narrow edentulous alveolar ridges and enable successful implant placement with shorter healing period compared with single guided bone regeneration.

Serum biomarkers for bisphosphonate-related osteonecrosis of the jaw: a prospective clinical study.

In this prospective study, serum levels of 12 possible biomarkers were compared between osteonecrosis of the jaw (ONJ) and control groups, before and after dentoalveolar surgery. The results suggest that patients with abnormal serum levels of specific biomarkers should be monitored closely for the prevention and early diagnosis of ONJ. INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaw (ONJ) is an adverse effect of long-term bisphosphonate therapy. This study aimed to identify bone biomarkers for ONJ risk assessment and diagnosis. METHODS: This prospective study included patients with histories of bisphosphonate therapy without current ONJ who were in need of dentoalveolar surgery of the jaw area. Serum levels of 12 possible bone markers, selected based on their involvement in ONJ pathogenesis, were compared between ONJ and control groups before dentoalveolar surgery (T0), at 8 postoperative weeks (T1), and at 4 months after diagnosis(T2). RESULTS: Seventy-six patients who met the inclusion criteria were included in the study; 33 were assigned to the ONJ group, and 43 patients without ONJ signs or symptoms after dentoalveolar surgery were assigned to the control group. In the ONJ group, at both T0 and T1, the mean tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) levels were significantly lower and the mean Dickkopf-related protein 1 (DKK1) levels were significantly higher than the corresponding values for the control group. Linear mixed model analysis revealed significant group effects over time for serum TRACP 5b and DKK1 after adjusting for demographic, pharmacological, and diagnostic variables. Lower serum levels of TRACP 5b under a specified cut-off value (≤ 2.899 U/L) at T0 indicated a 20.40-fold increased risk of ONJ development. CONCLUSION: Patients with abnormally low serum levels of TRACP 5b and high serum levels of DKK1 should be monitored closely before and after dentoalveolar surgery for the prevention and early diagnosis of ONJ.

Innovative method of alopecia treatment by autologous adipose-derived SVF.

BACKGROUND: Alopecia refers to a condition developed by gradual reduction of hair loss by various abnormal causes such as endocrine system, genetic factors, and stress. Stromal vascular fraction (SVF) isolated from the fat is one of the latest innovative solutions in the field of regeneration therapy. We focused on presenting effectiveness of clinical cases to improve AGA through transplantation of autologous SVF into the scalp. OBJECTIVE: To confirm the efficacy of the autologous SVF usage to the patients with AGA. METHODS: Nine patients (age range 43-64 years; 4 men, grade IV to V and 5 women, grade I to III), who are suffering from androgenic alopecia (AGA), were treated with single transplantation of autologous SVF in the upper scalp. Autologous SVF was isolated and characterized prior to the injection of live 7-9 × 106 cells into the patients' treatment site. The hair loss improvement effect was assessed by three test criteria: hair skin quality, hair thickness and hair density 3 and 6 months after post-injection compared to pre-injection status. RESULTS: Hair density of SVF-treated side was significantly increased after 3 and 6 months of transplantation compared to non-treated side (P = 0.01 and P = 0.009 per each). And significant improvement in the score of the keratin on the scalp was seen in the injected area as compared to the non-injected area 6 months after transplantation (P = 0.032). Although thickness increase was observed at 3 and 6 months after transplantation, there was no statistical significance (P = 0.142 and 0.155, respectively). CONCLUSIONS: One transplantation of autologous SVF for the AGA patients, hair density and score for the keratin were significantly increased within 6 months. This study shows that SVF is a very effective way to treat hair loss and most of subjects are satisfied with the result after treatment.

Medication-related osteonecrosis of the maxilla: Prognosis of oral surgery combined with endoscopic sinus surgery.

OBJECTIVES: To evaluate the effect of functional endoscopic sinus surgery (FESS) on the resolution of maxillary medication-related osteonecrosis of the jaw (MRONJ). PATIENTS AND METHODS: This study included 62 patients diagnosed with MRONJ in the maxillary posterior area with or without maxillary sinusitis (MS). All patients underwent oral surgery. The concomitant MS was evaluated, and if indicated, FESS was performed on the same operation. Follow-up included clinical and radiological examinations at 4 months postoperation. RESULTS: Of the 62 patients, 24 (38.7%) showed no evidence of MS and 38 (61.3%) showed MS. Advanced MRONJ (stage 3), which has bony destruction of the sinus floor and signs of MS according to its definition, was seen in 27 patients (43.5%). In stage 3 MRONJ, patients with combined treatment of oral surgery and FESS compared to those treated with oral surgery alone showed higher percentage of resolution (84.2%, 37.5%, respectively) at 4 months postoperatively, and the results were statistically significant. CONCLUSION: Simultaneous management of MRONJ and sinusitis with combined treatment of oral surgery and FESS for the treatment of maxillary MRONJ can be an effective method, especially for advanced cases, to address its associated lesions.

Pharmacoepidemiology and clinical characteristics of medication-related osteonecrosis of the jaw.

BACKGROUND: The aim of this study was to investigate clinical and pharmacoepidemiologic characteristics of medication-related osteonecrosis of the jaw. METHODS: The study population is comprised of 86patients who were diagnosed with ONJ at Ewha Womans University Mokdong Hospital from 2008 to 2015. Factors for epidemiologic evaluation were gender, age, location of lesion, and clinical history. The types of bisphosphonates, duration of intake, and the amount of accumulated dose were evaluated for therapeutic response. Clinical symptoms and radiographic images were utilized for the assessment of prognosis. RESULTS: Among the 86 patients, five were male, whereas 81 were female with mean age of 73.98 (range 45-97). Location of the lesion was in the mandible for 58 patients and maxilla in 25 patients. Three patients had both mandible and maxilla affected. This shows that the mandible is more prone to the formation of ONJ lesions compared to the maxilla. ONJ occurred in 38 cases after extraction, nine cases after implant surgery, six cases were denture use, and spontaneously in 33 cases. Seventy-six patients were taking other drugs aside from drugs indicated for osteoporosis. Most of these patients were diagnosed as osteoporosis, rheumatic arthritis, multiple myeloma, or had a history of cancer therapy. Higher weighted total accumulation doses were significantly associated with poorer prognosis (P < 0.05). CONCLUSION: Dose, duration, route, and relative potency of bisphosphonates are significantly associated with treatment prognosis of osteonecrosis of the jaw.

Impaired osseointegration of dental implants associated with orthognathic surgery: Possible regional acceleratory phenomenon.

BACKGROUND: Regional acceleratory phenomenon (RAP) is demonstrated to decrease regional bone mineral density and accelerate bone turnover. Hypothesizing that RAP can negatively affect the osseointegration of biomaterials, this study aimed to investigate the possible influence of the RAP on dental implant osseointegration. MATERIALS AND METHODS: Orthognathic surgery, one of the major surgeries on oral and maxillofacial region was set as intervention for RAP. Considering that RAP exerts its physiologic effects until 4 months after noxious stimuli, patients were classified according to the time interval between orthognathic surgery and dental implant installation; group I was designated to patients who had implant installation within 4 months from orthognathic surgery. Group II were those with installation after 4-12 months and group III was longer than 12 months. Radiographic and clinical evaluations of dental implants including peri-implant marginal bone changes (MBR), implant stability, cumulative survival rates were analyzed. RESULTS: A total of 54 patients with 106 implants (mean follow-up of 72.6 months) were included in the study. MBR was significantly higher in group I (2.62 ± 0.91 mm) and II (2.25 ± 0.95 mm) compared to that of group III (0.94 ± 0.90 mm) at last follow up (P < 0.05) and this group difference over time was also significant (P < 0.001). Compared to group III, groups I and II exhibited lower ISQ values and higher biological complications including peri-implantitis and peri-implant gingivitis (P < 0.05). Group I showed significantly low-cumulative survival rate (89.2%; implant-level) compared to groups II and III. CONCLUSIONS: In this study, impaired osseointegration of dental implants was demonstrated associated with orthognathic surgery. Micro-environmental changes of hard tissue induced by major surgery on the jaw showed deteriorating effects on integrity of biomaterial osseointegration. Special considerations should be addressed for ideal treatment results and prognosis.

A case of dystrophic calcification in the masseter muscle.

BACKGROUND: Dystrophic calcification can occur in any soft tissue with the absence of a systemic mineral imbalance and is often associated with trauma, infection, or inflammation. It is easily found in the site of the heart and skeletal muscles and rarely appears in the head and neck area. CASE REPORT: We present a rare case of multiple calcified masses in the left masseter muscle of a 26-year-old female with a history of trauma in the area. In computed tomography, multiple radiopaque masses were observed inside the left masseter muscle and blood test results were normal. The calcified masses were diagnosed as dystrophic calcification and removed by surgery without any complications. CONCLUSION: Different types of calcifications may occur in the cheek area, and they need to be distinguished from dystrophic calcification. Thorough clinical examination and history taking is required together with blood testing and radiographic examinations.

Malignant tracheal necrosis and fistula formation following palliative chemoradiotherapy: a case report.

Concurrent chemoradiotherapy is an essential treatment strategy for inoperable locally advanced non-small cell lung cancer (NSCLC). Although supportive care has improved, unexpected complications due to the disease or treatment can occur. Tracheomediastinal fistulas are very rare but can be a serious problem. Herein, we report a case of severe chondronecrosis of the distal trachea with formation of a fistula into a metastatic lymphadenopathy in a patient with stage IIIB NSCLC. The patient received external beam radiotherapy with a total dose of 35 Gy in 14 fractions, which was approximately half of the conventional therapeutic radiotherapy dose, along with concurrent cisplatin based chemotherapy. Careful evaluation, early detection, and timely intervention are essential to prevent and appropriately treat chondronecrosis, even in cases of low-dose radiotherapy application to central tumors.

Traumatic Buccal Fat Pad Herniation in Young Children: A Systematic Review and Case Report.

PURPOSE: Traumatic herniation of a buccal fat pad, predominantly seen in young children, is a rare condition. Because of its rarity and clinical features that resemble tumors, clinicians are faced with challenges at the initial diagnosis. This report describes a case of buccal fat pad herniation with excellent long-term prognosis after surgical relocation and conservative treatment and presents a systematic review of the literature on its management. MATERIALS AND METHODS: Through a PubMed search, 811 articles were initially identified. Case series, case reports, technical notes, case and review reports, and retrospective case series were included. After screening and manual review, the sample was narrowed to 35 reports (41 patients) based on eligibility criteria. Articles were included if the standard criteria for traumatic intraoral herniation of buccal fat pad were met. RESULTS: Patients' ages ranged from 4 months to 12 years, with no specific gender predilection. Management consisted of excision (82.9%), relocation (14.6%), and observation (2.4%). Follow-up ranged from 1 week to 4 months. No reports presented a follow-up longer than 4 months; hence, data on long-term prognosis were not reported. For the present case report, a 19-month-old boy diagnosed with traumatic buccal fat pad herniation was successfully treated with surgical relocation and antibiotic support. Twelve-month follow-up showed no esthetic or functional disturbance or recurrence. CONCLUSION: Traumatic herniation of the buccal fat pad requires special attention at the initial diagnosis. Considering its clinical importance in young children and few studies have reported long-term postresection follow-up, surgical relocation can be regarded as an excellent and more conservative treatment option.

Does the Addition of Bone Morphogenetic Protein 2 to Platelet-Rich Fibrin Improve Healing After Treatment for Medication-Related Osteonecrosis of the Jaw?

PURPOSE: To investigate the effect of the addition of bone morphogenetic protein 2 (BMP-2) to leukocyte-rich and platelet-rich fibrin (L-PRF) on the treatment of medication-related osteonecrosis of the jaws (MRONJ), this study compared the healing outcome of combined use of BMP-2 and L-PRF with single use of L-PRF. PATIENTS AND METHODS: Of 55 patients who were diagnosed with MRONJ, 25 were treated with L-PRF alone and 30 were treated with L-PRF and recombinant human BMP-2. For each patient, surgical sites were evaluated postoperatively at 4 and 16 weeks. Associations between the treatment method and the resolution of MRONJ were analyzed with the adjustment of patient-specific factors that may influence the treatment outcome. RESULTS: At 4 and 16 weeks postoperatively, patients with MRONJ who were treated with both L-PRF and BMP-2 showed favorable outcomes with complete resolution of the lesions, which was statistically significant compared with that of the therapy using L-PRF alone (P = .028). Therefore, the additional use of BMP-2 considerably improved MRONJ healing. Among patient-specific factors, the existence of a bacterial colony in the biopsy specimen was a significant factor that negatively affected disease resolution (P = .017). CONCLUSIONS: The combined use of BMP-2 and L-PRF leads to the early resolution of MRONJ; thus patients who need to continue antiresorptive therapy may benefit from the combined regimen.

The sequential management of recurrent temporomandibular joint ankylosis in a growing child: a case report.

BACKGROUND: Temporomandibular joint (TMJ) ankylosis in children often leads to facial deformity, functional deficit, and negative influence of the psychosocial development, which worsens with growth. The treatment of TMJ ankylosis in the pediatric patient is much more challenging than in adults because of a high incidence of recurrence and unfavorable growth of the mandible. CASE REPORT: This is a case report describing sequential management of the left TMJ ankylosis resulted from trauma in early childhood. The multiple surgeries including a costochondral graft and gap arthroplasty using interpositional silicone block were performed, but re-ankylosis of the TMJ occurred after surgery. Alloplastic TMJ prosthesis was conducted to prevent another ankylosis, and signs or symptoms of re-ankylosis were not found. Additional reconstruction surgery was performed to compensate mandibular growth after confirming growth completion. During the first 3 years of long-term follow-up, satisfactory functional and esthetic results were observed. CONCLUSIONS: This is to review the sequential management for the recurrent TMJ ankylosis in a growing child. Even though proper healing was expected after reconstruction of the left TMJ with costal cartilage graft, additional surgical interventions, including interpositional arthroplasty, were performed due to re-ankylosis of the affected site. In this case, alloplastic prosthesis could be an option to prevent TMJ re-ankylosis for growing pediatric patients with TMJ ankylosis in the beginning.

Perceptions of medical doctors on bisphosphonate-related osteonecrosis of the jaw.

BACKGROUND: This study aimed to investigate medical doctors' awareness of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and the status of dental referrals. METHODS: Self-administered questionnaires were distributed to medical doctors practicing internal medicine, family medicine, and orthopedics at the 6 tertiary medical centers located in Seoul, Korea. The survey consisted of 22 questions regarding the general characteristics, bisphosphonate therapy, awareness of BRONJ, and implementation of dental referrals. RESULTS: Among 192 medical doctors, 21.9 % had not heard of the disease. Only 8.9 % correctly answered all 5 questions testing BRONJ knowledge. Dental referrals made by medical doctors were implemented in less than 30 % of the total patients. Oncology specialists most often recognized the necessity of dental referrals followed in decreasing order by endocrinology, rheumatology, family medicine, and orthopedic specialists. CONCLUSION: Given medical doctors' low BRONJ perception and implementation level of dental referrals, enhancing information dissemination on BRONJ and development of a highly accessible educational program recognizing the need for dental referrals are urgent.

Midfacial Soft-Tissue Changes after Paranasal Augmentation with Porous Polyethylene.

The aim of this study was to determine the effect of porous polyethylene in paranasal augmentation on the overlying soft tissue. Thirty-three patients underwent paranasal augmentation using 3-mm-thick porous polyethylene and mandibular setback, and 35 patients underwent mandibular setback only. Lateral cephalograms were taken before and 6 months after the surgery to compare the soft-tissue changes in the paranasal area. Complications and patient satisfaction following the surgery were also analyzed. The average soft-tissue change in the paranasal area after the augmentation was 2.42 ± 0.33 mm, while there was no definite soft-tissue change in the paranasal area after mandibular setback alone. The ratio of soft-tissue changes to paranasal implant thickness was 80.7%. All patients in the augmentation group were satisfied with their surgical outcomes, which led to convex lateral profile with increase in midface volume. There were no complications such as postoperative infection or foreign body reaction requiring removal of implants. Paranasal augmentation using porous polyethylene is a predictable method providing minimal morbidity in patients with paranasal deficiency.

Biomarkers for Bisphosphonate-Related Osteonecrosis of the Jaw.

PURPOSE: The aim of this study was to investigate a possible biomarker for bisphosphonate-related osteonecrosis of the jaw (BRONJ) in an animal model. MATERIALS AND METHODS: Forty-eight Sprague-Dawley rats were randomly divided into the bisphosphonate group (n = 36), who were injected once a week with zoledronic acid, and the control group (n = 12), who were injected once a week with saline. After 6 weeks, surgical intervention was performed, and injections were continued up to 8 weeks. Rats in the bisphosphonate group were then further classified to the ONJ group, and the non-ONJ group, and biomarkers, including CTx, Glu-OC, TRACP 5b, RANKL, and OPG, were assessed at baseline (T0), at surgical intervention (T1), and at sacrifice (T2). Histomorphometric analysis for quantification of osteoclasts was performed. RESULTS: Repeated measures analysis of variance revealed that TRACP 5b levels and the RANKL/OPG ratio were significantly decreased over time in the ONJ group compared with the non-ONJ group (p < .05). At T2, the area under the curve was 0.807 for TRACP 5b (sensitivity: 88.9%, specificity 66.7% at cutoff) and 0.765 for the RANKL/OPG ratio (sensitivity: 77.8%, specificity 62.9% at cutoff). TRACP 5b showed a lower least significant change (29.6%) with lower intra-assay coefficient of variability (CV; 6.32%) and interassay CV (11.20%) compared with those of the RANKL/OPG ratio (39.27%) and showed a higher signal-to-noise ratio (2.76) than that of the RANKL/OPG ratio (1.62). N.Oc/T.Ar and N.Oc/B.Ar demonstrated significantly decreased number of osteoclasts in ONJ group versus non-ONJ group. CONCLUSIONS: These results show that serum TRACP 5b and the RANKL/OPG ratio were possible biomarkers for BRONJ. These data may provide useful additional information for future ONJ research. Further studies are needed to validate these results in humans with ONJ.

A Case of Cryptogenic Organizing Pneumonia after Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma.

Cryptogenic organizing pneumonia (COP) is an inflammatory lung disease involving the distal bronchioles, respiratory bronchioles, bronchiolar ducts, and alveolae. The etiology is usually unknown; however, there are several known causes and associated systemic diseases. Corticosteroid therapy is the best treatment option and the prognosis of COP is good, with recovery in up to 80% of patients. We described a patient with in-operable hepatocellular carcinoma (HCC) undergoing chemoembolization with doxorubicin in a drug-eluting bead (DEB). COP developed in the patient after chemoembolization but resolved spontaneously in several months.

Clinical features of lung adenocarcinomas with epidermal growth factor receptor mutations and miliary disseminated carcinomatosis.

BACKGROUND: We have occasionally encountered advanced lung cancer patients with disseminated carcinomatosis throughout the body and/or within the lung. This study investigated the clinical characteristics and outcomes of advanced lung adenocarcinoma patients with miliary disseminated carcinomatosis. METHODS: Patients with adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations who presented with miliary disseminated carcinomatosis (either intrapulmonary or distant site) were enrolled in the study. Clinical characteristics, treatment responses, and survival outcomes were collected from medical records. RESULTS: The most frequent EGFR mutation was an in-frame deletion in exon 19 (n = 44, 68.8%). Arginine substitution of leucine 858 in exon 21 and alanine substitution of glycine 719 in exon 18 were detected in 19 patients (29.7%) and one patient (1.6%), respectively. Patients with miliary disseminated carcinomatosis tended to be female and non-smokers. They expressed the E19 deletion more frequently than patients without miliary dissemination and had shorter progression-free survival times in response to EGFR tyrosine kinase inhibitors (9.7 vs. 12.8 months, P = 0.003) and poorer overall survival (15.9 vs. 29.0 months, P = 0.077). Multivariate analyses revealed that metabolic tumor volume correlated with shorter overall survival time. CONCLUSIONS: Our data indicate that lung adenocarcinoma patients with miliary dissemination have relatively shorter survival times than those without miliary dissemination. The poor prognosis of patients with miliary dissemination may reflect a high tumor burden, as represented by metabolic tumor volume.

Animal model for medication-related osteonecrosis of the jaw with precedent metabolic bone disease.

Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group (n=48) and sham-operated group (n=48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n=36 each) and control group (n=12 each) and injected with zoledronic acid and normal saline, respectively, once a week. After additional 6weeks, surgical intervention was performed, and the injections were continued for 8 more weeks. The animals were then sacrificed for further macroscopic, histological, histomorphometric, radiological, and bone biomarker investigations. As histologically determined, the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group (47.2%; P<0.05). Micro-structural and histomorphometric assessments revealed that rats with ONJ (ONJ group) presented with deteriorated bone architectures with higher necrotic bone fraction and lower number of osteoclasts (P<0.05). Compared to the sham-operated ONJ group, the Ov ONJ group showed significantly lower values of Tb.N, Tb.Sp, Conn.D, N.Oc/T.Ar, and TRACP 5b and CTX/TRACP (P<0.05). The ovariectomized rat model in this study successfully mimicked human ONJ lesions with an underlying bone disease and showed different bone characteristics than that of the previous ONJ model. Based on the differences, further researches for investigating pathophysiology of ONJ, including various pharmacological responses for deteriorated bone environment, are required.