Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy.

BACKGROUND: Adoptive transfer of in vitro expanded tumor-infiltrating lymphocytes (TILs) has been effective in regressing several types of malignant tumors. This study assessed the yield and factors influencing the successful expansion of tumor-infiltrating lymphocytes (TILs) from head and neck squamous cell carcinoma (HNSCC), along with their immune phenotypes. METHODS: TILs were expanded from 47 surgically resected HNSCC specimens and their metastasized lymph nodes. The cancer tissues were cut into small pieces (1-2 mm) and underwent initial expansion for 2 weeks. Tumor location, smoking history, stromal TIL percentage, human papillomavirus infection, and programmed death-ligand 1 score were examined for their impact on successful expansion of TILs. Expanded TILs were evaluated by flow cytometry using fluorescence-activated cell sorting. A second round of TIL expansion following the rapid expansion protocol was performed on a subset of samples with successful TIL expansion. RESULTS: TILs were successfully expanded from 36.2% samples. Failure was due to contamination (27.6%) or insufficient expansion (36.2%). Only the stromal TIL percentage was significantly associated with successful TIL expansion (p = 0.032). The stromal TIL percentage also displayed a correlation with the expanded TILs per fragment (r = 0.341, p = 0.048). On flow cytometry analysis using 13 samples with successful TIL expansion, CD4 + T cell dominancy was seen in 69.2% of cases. Effector memory T cells were the major phenotype of expanded CD4 + and CD8 + T cells in all cases. CONCLUSION: We could expand TILs from approximately one-third of HNSCC samples. TIL expansion could be applicable in HNSCC samples with diverse clinicopathological characteristics.

Is conservative treatment (enucleation using modified Carnoy's solution) of odontogenic keratocyst in the maxilla good prognosis?

Odontogenic keratocysts (OKCs) located in the maxillae have rarely been reported in the literature. Standard treatment modalities for OKC range from marsupialization to marginal resection. However, most of the studies on OKC treatment have been related to mandibular OKCs. The anatomical structure and loose bone density of the maxillae and the empty space of the maxillary sinus could allow rapid growth of a lesion and the ability to tolerate tumor occupancy in the entire maxilla within a short period of time. Therefore, OKCs of the maxillae require more aggressive surgery, such as resection. As an alternative, this report introduces a modified Carnoy's solution, a strong acid, as an adjuvant chemotherapy after cyst enucleation. This report describes the clinical outcomes of enucleation using a modified Carnoy's solution in patients with large OKCs on the posterior maxillae. In three cases, application of a modified Carnoy's solution had few side effects or morbidity. Each patient was followed for four to six years, and none showed any signs of recurrence. In conclusion, adjuvant treatment with a modified Carnoy's solution can be considered a treatment option capable of reducing the recurrence rate of OKC in the maxillae.

Case series and technical report of nasal floor approach for mesiodens.

Objectives: This case series aims to introduce the nasal floor approach for extracting inverted mesiodens. Materials and Methods: Through a retrospective chart review between January 2022 and February 2023, we included the mesiodens patients using nasal floor approach, and analysis the location of mesiodens from the anterior nasal spine (ANS), total operation time, and complications. Results: Each mesiodens was located 10 to 12 mm from the ANS and was covered with a cortical layer of the nasal floor. All mesiodens were successfully extracted without exposing the adjacent incisors or nasopalatine nerve within 30 minutes from draping to postoperative dressing. Conclusion: The nasal floor approach is an efficient extraction method that reduces bone removal and prevents anatomical damage while removing the mesiodens just below the nasal floor bone.

ATRX protein is a potential prognostic marker in clear cell renal cell carcinoma.

Objective: Cancer cells activate either telomerase or alternative lengthening of telomeres (ALT) to maintain telomere length and achieve immortalization. Alpha thalassemia/mental retardation X-linked (ATRX) is involved in chromatin remodeling. Mutations in ATRX genes are associated with the loss of nuclear expression and correlated with the ALT phenotype. ATRX expression has been evaluated in various cancers, especially sarcoma and neuroendocrine tumors, and its clinical significance has been shown to be diverse, depending on the tumor types. The role and prognostic value of ATRX expression in clear cell renal cell carcinoma (CCRCC) have not been elucidated. Methods: We investigated the messenger RNA (mRNA) expression levels of ATRX using the gene expression profiling interactive analysis (GEPIA) database and evaluated the expression of ATRX using immunohistochemical (IHC) staining in 302 CCRCC cases. Results: Loss of ATRX expression was significantly associated with larger tumor size, higher nuclear grade (NG), lymphovascular invasion (LVI), pathologic T (pT) stage, recurrence/metastasis, and stage. Although ATRX was not an independent prognostic factor, patients with loss of ATRX expression showed poor survival. Conclusion: Our findings suggest that loss of ATRX expression could be a potential biomarker for predicting aggressive tumor behavior and poor clinical outcomes in CCRCC.

Coronoidectomy for reduction of superolateral dislocation of mandible condyle.

Superolateral dislocation of the condyle is a rare mandibular fracture. The treatment goal is to return the dislocated condyle to its original position to recover normal function. This study reports on superolateral dislocation of the condyle with mandibular body fracture. The mandibular body was completely separated, and the medial pole of the condyle head was fractured. The condyle segment was unstable and easily dislocated after reduction. The temporalis muscle on the condyle segment might have affected the dislocation of the condyle. A coronoidectomy was performed to disrupt the function of the temporalis muscle on the condyle segment in order to successfully reduce the dislocated condyle. Coronoidectomy is a simple procedure with minimal complications. We successfully performed a coronoidectomy to reduce the superolateral displaced condyle to its original position to achieve normal function. Coronoidectomy can be effectively used for reduction of superolaterally displaced condyles combined with severe maxilla-mandibular fractures.

Speech-aid prosthesis in velopharyngeal incompetency patient with cleft palate: can speech aids be applicable for adult patient?

BACKGROUND: Velopharyngeal incompetence (VPI) therapy for cleft palate (speech therapy alone, speech therapy using speech aids, or combined therapy such as speech therapy using a pharyngeal flap), is more effective in younger patients than in adult patients. Speech therapy is known as very difficult for patients who still have VPI as an adult. Because of the possibility of subsequent speech disorders, the timing of surgery for cleft palate is accelerating. Herein, we present a case of an adult with articulation disorder due to VPI who was treated by speech therapy and a speech-aid prosthesis. CASE PRESENTATION: A woman who underwent cleft palate surgery at 8 years of age still had difficulty with articulation due to VPI as a 24-year-old adult because of a lack of continuous speech therapy. We decided to use a speech-aid application using palatal lift, and a reduction program was conducted four times, along with simultaneous speech therapy, over a period of 1 year and 7 months. During the therapy period, she was able to speak normally within a relatively short period of time, and after implementation of the reduction program, the therapy was completed by completely removing the device. Long-term observations have shown normal speech function without recurrence, even after the device was removed. CONCLUSION: As seen in this case, speech therapy using speech aids can show a good result for adult patients with cleft palate who missed the usual timing for the treatment of articulation disorders, depending on the situation. Therefore, it is hereby reported as a therapy option worthy of consideration.

Conservative management with Carnoy's solution in ameloblastoma involving two unerupted teeth: a report of two cases.

Marsupialization is widely used as a primary treatment modality for reducing size of large cysts. However, there is no recommendation for specific duration of marsupialization. In addition, Carnoy's solution usually is applied at the time of enucleation as a fixative agent. In this report, we present an appropriate marsupialization duration of ameloblastoma involving two unerupted teeth. In this present study, marsupialization using a Foley catheter was performed in two cases of ameloblastoma of the mandible involving two adjacent impacted teeth. Carnoy's solution was applied for 3-5 minutes after enucleation in both patients. Periodically during marsupialization, the size of the radiolucency was measured in panoramic view, and clinical examination was performed. No remarkable paresthesia or soft tissue injury was observed after application of Carnoy's solution or during follow-up. We recommend 12 to 16 weeks as an adequate marsupialization duration for a large ameloblastoma involving two impacted teeth based on increased radiopacity along the margins of the lesions. Poor oral hygiene was an issue after 12 weeks of marsupialization in one case. There were no remarkable complications with Carnoy's solution in either case. The Foley tube has a two-way system that is more effective for irrigating the cavity than is the conventional one-way system.

High MCM6 Expression as a Potential Prognostic Marker in Clear-cell Renal Cell Carcinoma.

AIM: Minichromosome maintenance (MCM) proteins are involved in initiation of DNA replication and cell-cycle progression. Loss of MCM function results in genomic instability and causes carcinogenesis. Among MCM genes, the role and prognostic value of MCM6 expression in clear-cell renal cell carcinoma (ccRCC) has not been elucidated. MATERIALS AND METHODS: We assessed the mRNA expression level of MCM6 using the Gene Expression Profiling Interactive Analysis database and investigated MCM6 protein expression by immunohistochemistry in 238 ccRCC cases. RESULTS: High MCM6 expression was significantly associated with increasing tumor size, pT, stage, tumor necrosis, and metastasis. Furthermore, high MCM6 expression was significantly associated with shorter overall and disease-free survival, and was an independent unfavorable prognostic marker. Regarding patients with metastasis, high MCM6-expressing ccRCC conferred significantly shorter survival than for those with low expression. CONCLUSION: A high MCM6 expression level may be a promising biomarker to predict tumor progression, metastasis, and survival in patients with ccRCC.

An unusual presentation of non-specific cystic degeneration of craniofacial fibrous dysplasia: a case report and review of literature.

BACKGROUND: Fibrous dysplasia (FD) is a rare, sporadic, and benign congenital condition in which normal cancellous bone is replaced by fibro-osseous tissue with immature osteogenesis. FD localized in the cranial and facial bones is called craniofacial fibrous dysplasia (CFD). Cystic degeneration in CFD cases is rare; cystic degeneration appearing in both the maxilla and the mandible FD lesion is even rarer. The aim of this article was to report a case of fibrous dysplasia of the mandible and maxilla complicated by nonspecific cystic degeneration. CASE PRESENTATION: A 30-year-old woman presented with a rare case of non-specific cystic degeneration in a mandible and maxilla FD lesion that occurred 11 years after surgery. She was diagnosed with polyostotic CFD and underwent maxillary and mandibular bone contouring. Cyst enucleation under general anesthesia was performed in the mandibular region due to pain and discomfort. CONCLUSIONS: In cases involving non-aggressive and non-invasive FD cystic degeneration in focal areas, conservative treatment is recommended. However, if cystic degeneration of FD develops rapidly and causes discomfort, pain, or dysfunction, surgical treatment should be considered.

A clinical study of inferior alveolar nerve damage caused by Carnoy's solution used as a complementary therapeutic agent in a cystic lesion.

BACKGROUND: Cyst enucleation, which extracts only the tumor with the application of Carnoy's solution (CS), has been suggested as a conservative treatment with a low recurrence rate and morbidity. However, there has been a concern that CS's contact with inferior alveolar nerve (IAN) can cause neurons to degenerate and cause sensory dysfunction. The purpose of this retrospective cohort study aimed to investigate the neurosensory function after surgical treatment with or without the application of CS. METHODS: While controlling the effects of sex, age, follow-up period, and invasion size of the tumor, we performed the binary logistic regression analysis to examine whether or not the sensory function of the patients who were treated with CS (n = 19) for the cyst enucleation procedure was significantly different from those who were not treated with CS (n = 58) at the end of the follow-up period. RESULTS: The logistic regression result showed that the use of CS was not significantly related to the normalness of sensory function at the end of the follow-up period. Rather, the invasion size of the cyst was significantly associated with sensory dysfunction. CONCLUSIONS: CS may be used for patients who are diagnosed with OKC and UAM without much fear of its impact on sensory dysfunction. However, a small number of patients who were treated with CS experienced severe sensory damage and did not recover at the end of the follow-up period, suggesting the need for further analysis of these patients.

Treatment of velopharyngeal insufficiency in a patient with a submucous cleft palate using a speech aid: the more treatment options, the better the treatment results.

BACKGROUND: The submucous cleft palate (SMCP) is a type of cleft palate that may result in velopharyngeal insufficiency (VPI). Palate muscles completely separate oral and nasal cavities by closing off the velopharynx during functional processes such as speech or swallow. Also, hypernasality may arise from anatomical or neurological abnormalities in these functions. Treatments of this issue involve a combination of surgical intervention, speech aid, and speech therapy. This case report demonstrates successfully treated VPI resulted from SMCP without any surgical intervention but solely with speech aid appliance and speech therapy. CASE PRESENTATION: A 13-year-old female patient with a speech disorder from velopharyngeal insufficiency that was caused by a submucous cleft palate visited to our OMFS clinic. In the intraoral examination, the patient had a short soft palate and bifid uvula. And the muscles in the palate did not contract properly during oral speech. She had no surgical history such as primary palatoplasty or pharyngoplasty except for tonsillectomy. And there were no other medical histories. Objective speech assessment using nasometer was performed. We diagnosed that the patient had a SMCP. The patient has shown a decrease in speech intelligibility, which resulted from hypernasality. We decided to treat the patient with speech aid (palatal lift) along with speech therapy. During the 7-month treatment, hypernasality measured by a nasometer decreased and speech intelligibility became normal. CONCLUSIONS: Surgery remains the first treatment option for patients with velopharyngeal insufficiencies from submucous cleft palates. However, there were few reports about objective speech evaluation pre- or post-operation. Moreover, there has been no report of non-surgical treatment in the recent studies. From this perspective, this report of objective improvement of speech intelligibility of VPI patient with SMCP by non-surgical treatment has a significant meaning. Speech aid can be considered as one of treatment options for management of SMCP.

CD9 Expression in Tumor Cells Is Associated with Poor Prognosis in Patients with Invasive Lobular Carcinoma.

PURPOSE: We investigated the prognostic significance of CD9 expression in tumor cells of patients with invasive lobular carcinoma (ILC). METHODS: CD9 expression was evaluated by immunohistochemistry in 113 ILC tissue samples. Correlation of CD9 expression with the patients' clinicopathological parameters and overall survival was assessed. RESULTS: CD9 expression was detected in 48 (42.5%) ILC patients. However, no significant relation could be determined between CD9 expression and the clinicopathological parameters of the patient including tumor size, lymph node metastasis, lymphovascular invasion, histologic grade, expression of hormone receptors, human epidermal growth factor receptor 2 status, and Ki-67 labeling index. Patients with CD9 expression had worse overall survival (p = 0.051) and disease-free survival (DFS, p = 0.014) compared to patients without CD9 expression. Multivariate analysis revealed that CD9 expression was an independent prognostic factor for DFS (p = 0.049). CONCLUSION: CD9 expression in tumor cells could be a significant prognostic marker in patients with ILC.

Ankylosis of the Coronoid Process to the Zygomatic Bone: A Case Report and Review of the Literature.

PURPOSE: Extra-articular temporomandibular bony ankylosis between the zygomatic bone and coronoid process is a rare condition. Currently, there are fewer than 40 cases reported in the English-language literature. The aim of this study was to report a case of zygomatico-coronoid ankylosis with surgical intervention and a literature review. MATERIALS AND METHODS: Through a PubMed search from 1946 to February 2018, using the terms ("extra-capsular" OR "zygomatico-coronoid" OR "extra-articular") AND ("ankylosis"), 61 articles were initially identified. After screening, manual reviewing, and including additional articles through reviews of the reference lists, 26 reports (33 patients) were included in the analysis. RESULTS: Patients' age ranged from 12 to 71 years (mean, 36.62 yr; standard deviation, 16.24 yr). The gender composition of patients was male (n = 20; 60.6%), female (n = 12; 36.4%), and unknown (n = 1; 0.3%), with a clear male predominance. The etiologies were trauma (n = 25; 75.8%), infection (n = 3; 9.1%), surgical complication (n = 4; 12.1%), and radiotherapy for maxillary cancer (squamous cell carcinoma; n = 1; 3.0%). The treatment options were surgical intervention through an intraoral approach (n = 19; 57.6%), an extraoral approach (n = 10; 30.3%), and intraoral and extraoral approaches (n = 2; 6.1%) and nonsurgical intervention (n = 2; 6.1%). CONCLUSION: Zygomatico-coronoid ankylosis is a possible cause of mouth-opening limitation, particularly in relation to facial trauma. However, it can be easily overlooked because of the rarity of zygomatico-coronoid ankylosis and the attention focused on the joint. Surgical intervention is regarded as a good treatment to improve mouth-opening limitation.

Ovarian Gynandroblastoma with a Juvenile Granulosa Cell Tumor Component in a Postmenopausal Woman: A Case Report and Literature Review.

Gynandroblastoma is an extremely rare sex cord-stromal tumor with both female (granulosa cell tumor) and male (Sertoli-Leydig cell tumor) elements. Juvenile granulosa cell tumors are also very rare and are so named because they usually occur in children and adolescents. A 71-year-old woman with right upper quadrant abdominal pain visited our hospital. Pelvic computed tomography showed a large multilocular cystic mass, suspected to be of ovarian origin. We performed a total abdominal hysterectomy (total abdominal hysterectomy was performed) with bilateral salpingooophorectomy. A 13-cm multilocular cystic mass with serous fluid was observed in her right ovary. Upon microscopic examination, the solid component of the mass showed both Sertoli-Leydig cell and juvenile granulosa cell differentiation, which we diagnosed as gynandroblastoma. Gynandroblastoma with a juvenile granulosa cell tumor component is extremely rare and, until now, only six cases have been reported in the English literature. We report the first gynandroblastoma with a juvenile granulosa cell tumor component diagnosed in an elderly patient, along with a literature review.

Utility of sodium tetradecyl sulfate sclerotherapy from benign oral vascular lesion.

BACKGROUND: Hemangioma and vascular malformation are benign vascular lesions that often occur in cephalic and cervical region. Currently, surgical resection, laser therapy, angiographic embolization, use of steroids, and sclerotherapy are used as treatments. CASE PRESENTATION: This study reports three cases of benign vascular lesions that are remarkably treated by sodium tetradecyl sulfate (STS) injection, of which occurred in oral cavity and around the mouth. Three percent of STS was diluted with 0.9 % of normal saline, and it was injected to the lesion site at least once. The result of treatment was evaluated based on clinical findings. CONCLUSION: Surgical treatment of hemangioma and vascular malformation occurred in oral cavity is not normally used because of esthetic issues and potential hemorrhage. On the other hand, sclerotherapy using STS is an effective therapy compare to surgical treatment. Despite the number of STS injection was different for each patient, all three patients had reached satisfactory level through the treatment with gradual diminution of lesions.

Requirement of Smad4-mediated signaling in odontoblast differentiation and dentin matrix formation.

Dentin is the major part of tooth and formed by odontoblasts. Under the influence of the inner enamel epithelium, odontoblasts differentiate from ectomesenchymal cells of the dental papilla and secrete pre-dentin which then undergo mineralization into dentin. Transforming growth factor-beta (TGF-ß)/bone morphogenetic protein (BMP) signaling is essential for dentinogenesis; however, the precise molecular mechanisms remain unclear. To understand the role of TGF-ß/BMP signaling in odontoblast differentiation and dentin formation, we generated mice with conditional ablation of Smad4, a key intracellular mediator of TGF-ß/BMP signaling, using Osr2 or OC-Cre mice. Here we found the molars of Osr2CreSmad4 mutant mice exhibited impaired odontoblast differentiation, and normal dentin was replaced by ectopic bone-like structure. In Osr2CreSmad4 mutant mice, cell polarity of odontoblast was lost, and the thickness of crown dentin was decreased in later stage compared to wild type. Moreover, the root dentin was also impaired and showed ectopic bone-like structure similar to Osr2CreSmad4 mutant mice. Taken together, our results suggest that Smad4-dependent TGF-ß/BMP signaling plays a critical role in odontoblast differentiation and dentin formation during tooth development.

Manifestation and treatment in a cleidocranial dysplasia patient with a RUNX2 (T420I) mutation.

Cleidocranial dysplasia is an autosomal dominant heritable skeletal disorder. The characteristic features of cleidocranial dysplasia (CCD) may include hypoplasia of the clavicle, delayed closure of frontanelles, late tooth eruption, and other skeletal disorders. This case report describes clinical and radiographic manifestations at the age of 11 and 29 of a CCD patient, investigates the mutation of core-binding factor A1 (CBFA1) based on gene analysis, and illustrates successful oral reconstruction with fixed prosthesis and dental implant after the extraction of multiple teeth.

Rice hull extracts inhibit proliferation of MCF-7 cells with G1 cell cycle arrest in parallel with their antioxidant activity.

Rice (Oryza sativa L.) has been a major dietary staple worldwide for centuries. Growing interest in the beneficial effects of antioxidants has inspired investigation of rice hulls as an attractive source of chemopreventive compounds for breast cancer intervention. We prepared methanol extracts from rice hulls of three Korean bred cultivars (japonica), Ilpum, Heugjinju, and Jeogjinju, and one japonica weedy rice, WD-3. We examined the antiproliferative potential of the hull extracts on MCF-7 human breast cancer cells and the related mechanisms thereof. Hull extracts inhibited proliferation of the cells and mediated G0/G1 phase arrest by suppressing cyclins and cyclin-dependent kinases, where WD-3 extract showed the most potent. Blockage of p21 expression by small interfering RNA transfection attenuated G1 phase arrest induced by WD-3 extract. The WD-3 extract exhibited greater antioxidant potential and total phenolic compounds, compared with other rice hulls. Gas chromatography-mass spectrometry analysis for the F4 fractioned from WD-3 extract revealed that cinnamic acid derivatives were the major active constituents. The F4 fraction most potently inhibited proliferation of MCF-7 cells than WD-3 extract through the suppression of cell cycle regulatory factors. Collectively, our results suggest that the pigmented rice hulls possess greater antioxidant and chemopreventive activity against breast cancer than the other rice cultivars tested, demonstrating that WD-3 rice hulls are an attractive source of chemopreventive bioactive compounds.