Ultrasonography predicts the results of labial salivary gland biopsy in patients with suspected Sjögren's syndrome: a matrix risk model.

OBJECTIVE: Although a positive result of labial salivary gland biopsy (LSGB) is critical for the diagnosis of Sjögren's syndrome, rheumatologists prefer assessing the non-invasive objective items and hope to learn the predicted probability of positive LSGB before referring patients with suspected Sjögren's syndrome to receive biopsy. This study aimed to explore the predictive value of combined B-mode ultrasonography (US) and shear-wave elastography (SWE) examination on LSGB results. METHODS: A derivation cohort and later a validation cohort of patients with suspected Sjögren's syndrome were recruited. All participants received clinical assessments, B-mode US and SWE examination on bilateral parotid and submandibular glands before LSGB. Positive LSGB was defined by a focus score ⩾1 per 4 mm2 of glandular tissue. RESULTS: In the derivation cohort of 91 participants, either the total US scores or the total SWE values of four glands significantly distinguished patients with positive LSGB from those with negative results (area under the curve (AUC) = 0.956, 0.825, both p < 0.001). The positive predictive value (PPV) was 100% in patients with total US scores ⩾9 or with total SWE values ⩾33 kPa. The negative predictive value (NPV) was 100% in patients with total US scores <5, but 68% in patients with total SWE values <27 kPa. A matrix risk model was derived based on the combination of total US scores and total SWE values. Patients can be stratified into high, moderate, and low risk of positive LSGB. In the validation cohort of 52 participants, the PPV was 94% in the high-risk subpopulation and the NPV was 93% in the low-risk subpopulation. CONCLUSION: A novel matrix risk model based on the combined B-mode US and SWE examination can help rheumatologists to make a shared decision with suspected Sjögren's syndrome patients on whether the invasive procedure of LSGB should be performed.

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-Specific CAR T Cells in Solid Tumors.

PURPOSE: The limited efficacy of chimeric antigen receptor (CAR) T-cell therapies with solid malignancies prompted us to test whether epigenetic therapy could enhance the antitumor activity of B7-H3.CAR T cells with several solid cancer types. EXPERIMENTAL DESIGN: We evaluated B7-H3 expression in many human solid cancer and normal tissue samples. The efficacy of the combinatorial therapy with B7-H3.CAR T cells and the deacetylase inhibitor SAHA with several solid cancer types and the potential underlying mechanisms were characterized with in vitro and ex vivo experiments. RESULTS: B7-H3 is expressed in most of the human solid tumor samples tested, but exhibits a restricted expression in normal tissues. B7-H3.CAR T cells selectively killed B7-H3 expressing human cancer cell lines in vitro. A low dose of SAHA upregulated B7-H3 expression in several types of solid cancer cells at the transcriptional level and B7-H3.CAR expression on human transgenic T-cell membrane. In contrast, the expression of immunosuppressive molecules, such as CTLA-4 and TET2, by T cells was downregulated upon SAHA treatment. A low dose of SAHA significantly enhanced the antitumor activity of B7-H3.CAR T cells with solid cancers in vitro and ex vivo, including orthotopic patient-derived xenograft and metastatic models treated with autologous CAR T-cell infusions. CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.

Comparison of 3 techniques of surgical treatment of carotid body tumors.

OBJECTIVE: Carotid body tumors (CBTs) are benign but challenging. This study compared outcomes of 3 techniques of the surgical treatment of CBTs. STUDY DESIGN: This retrospective observational study was conducted from April 2013 to March 2019. The 38 patients enrolled in the study had primary tumors, including 1 with bilateral tumors and another with adrenal gland pheochromocytoma. We collected data on age, sex, size of tumor, Shamblin classification, treatment, blood loss, operative time, hospital stay, complications, and recurrence. Statistical analyses were performed using IBM SPSS Statistics version 20 software. RESULTS: Twenty-four patients were male, and 12 were female, and they ranged in age from 11 to 71 years. Cases were assigned to Shamblin groups I (n = 6), II (n = 19), and III (n = 14). Tumor size ranged from 2.0 × 2.0 cm to 5.0 × 6.0 cm. Eleven CBTs underwent blunt dissection (BD), 20 underwent BD plus resection of external carotid artery division plus vessels of encapsulation with allograft dermal matrix (BD + RECA + VE), and 8 tumors underwent surgical resection of tumors plus common carotid artery-internal carotid artery artificial vascular reconstruction (SR +C-IAVR). No perioperative death or stroke occurred. There was a significant difference between Shamblin groups I, II, and III in terms of the size of the tumor, type of treatment used, blood loss, operative time, hospital stay, and complications. Six patients had mandibular branch facial nerve transient paresis; 7 patients had hypoglossal nerve dysfunction; 3 patients had Horner syndrome; and dysphasia occurred in 2 patients. The patients were seen in follow-up for 16 to 45 months, and 1 recurrence was observed. CONCLUSIONS: Three surgical techniques-BD, BD + RECA + VE, and SR + C-IAVR-are safe and feasible for the treatment of CBTs according to Shamblin classifications.

Vermilionectomy followed by reconstruction of the vermilion mucosa using allograft dermal matrix in patients with actinic cheilitis of the lower lip.

BACKGROUND: When treating actinic cheilitis (AC), it is essential to minimize the risk of malignant transformation (MT) and maintain lip functionality and cosmesis. AIMS: We evaluated the outcomes of vermilionectomy followed by reconstruction of the vermilion mucosa using allograft dermal matrix (ADM) in patients with AC of the lower lip. MATERIALS AND METHODS: We evaluated eight patients with lower lip AC who underwent vermilion mucosa reconstruction using ADM after vermilionectomy. We enrolled five males and three females ranging in age from 55 to 70 years (mean, 62.1 years). The ADM ranged in area from 1.3 × 5.0 to 1.7 × 5.8 cm (median, 1.6 × 5.5 cm). All patients were followed up for at least 3 months postoperatively by a panel of three surgeons who assessed the esthetic results, and orbicularis oris and speech functions. RESULTS: All patients underwent successful reconstruction of the vermilion mucosa using ADM after vermilionectomy, without complications. The postoperative esthetic results, and the orbicularis oris and speech functions, were satisfactory to excellent in all patients. Patients were followed up for 18-38 months (median, 26.1 months). No MT or recurrence was noted. CONCLUSIONS: Vermilionectomy followed by reconstruction of the vermilion mucosa with ADM is safe and feasible for AC patients.

Comparison of postoperative cytokine and hormone between endoscopically assisted and open parotid tumor resection.

OBJECTIVE: Endoscopically assisted extracapsular dissection through a single incision along the cephaloauricular furrow has been adapted as a method of access for operating on benign parotid gland tumors. However, no study has compared the immune and stress responses after surgery between the endoscopic procedure and conventional open surgery. METHODS: Through a randomized method, 50 patients with benign parotid gland tumors were assigned to undergo either endoscopically assisted extracapsular dissection or open parotidectomy. The postoperative inflammatory changes and hormonal response in the patients were analyzed at serum level during the preoperative period and at 12, 24, and 72 hr after either surgery. RESULTS: Twenty-three patients received an endoscopic procedure, while 27 underwent open surgery. The size of the incision, amount of intraoperative bleeding, volume of drainage, postoperative pain score, and satisfaction with appearance were all improved in the endoscopic procedure group. Additionally, the serum levels of C-reactive protein, interleukin (IL)-6, IL-10, and cortisol were significantly lower in the endoscopy group in comparison with those in the open surgery group. CONCLUSION: Endoscopically assisted extracapsular dissection on patients with benign parotid gland tumors is associated with lower inflammatory changes and hormone responses than open surgery, thereby reducing perioperative pathophysiological disturbance and enhancing recovery after surgery.

A Dexamethasone-Eluting Porous Scaffold for Bone Regeneration Fabricated by Selective Laser Sintering.

Additive manufacture (AM) has been widely and rapidly applied in fabrication of 3D porous scaffolds for tissue engineering applications. For synthetic polymers of high melting temperature, the melting-extruding technique is the most applied AM method for such fabrication of polymer porous scaffolds. This results in a big challenge to directly process the scaffolds using the polymers and thermosensitive substances simultaneously because of deactivation under high temperature. In this article, the selective laser sintering (SLS) method was proposed to make a poly(l-lactic acid) (PLLA) porous scaffold containing dexamethasone (Dex) simultaneously. Dex was encapsulated in two groups of PLLA-bioactive glass (BG) composite microspheres with an average diameter of 115-120 µm and loading amounts of 0.68 ± 0.09 and 0.84 ± 0.10 µg/mg, respectively. The drug-loading composite microspheres were then fabricated into scaffolds under a laser fluence of 0.83-2.08 J/mm2. The average pore size and compressive modulus for the porous scaffold were 450-500 µm and 18-25 MPa, respectively. Drug release experiments showed that Dex was released from the scaffold in a controlled manner until about a month. The eluting time of HPLC tests before or after SLS processing both presented at 4 min indicated no chemical structure changes for the drug. Ex vivo cell experiments also testified the comparable effect of released Dex with commercial products, showing that the bioactivities were not affected after SLS. Implantation of the composite scaffolds in rat cranium defects demonstrated that new bone and blood vessel formation was faster in the Dex-releasing scaffolds than in the groups without drug loading.

Reconstruction of Large Anterior Palatal Fistulae Using Anteriorly Based Dorsal Tongue Flaps.

BACKGROUND: An anterior palatal fistula in a bilateral cleft lip and palate is a challenging clinical dilemma. The authors evaluate the feasibility and outcomes of the reconstruction of large anterior palatal fistulae using anteriorly based dorsal tongue flaps. METHODS: Eight patients with anterior palatal fistulae after repair of a bilateral cleft lip and palate using anteriorly based dorsal tongue flaps. The defect size varied from 1.0 × 1.0 cm to 1.5 × 2.0 cm, and the tongue flap size varied from 1.5 × 3.5 cm to 2.0 × 3.5 cm. RESULTS: All patients underwent successful reconstruction of palatal defects using anteriorly based tongue flaps, and no case of spontaneous detachment of the tongue flap occurred. The patients with palatal fistulae were followed up for 10 to 30 months, and no recurrence was encountered. CONCLUSION: An anteriorly based dorsal tongue flap is a safe and feasible surgical technique for the closure of anterior palatal fistulae.

Use of an anteriorly based ventral tongue flap to reconstruct the lower vermilion following early-stage cancer ablation.

BACKGROUND: Reconstruction of lower vermilion defects is surgically challenging. AIMS: This study evaluated whether lower vermilion defects can be repaired using tongue flaps, and the reconstructive outcomes. MATERIALS AND METHODS: We evaluated 11 patients with early-stage lower vermilion cancers who underwent lower vermilion reconstruction using anteriorly based ventral tongue flaps following cancer ablation. We treated eight males and three females aged 54-67 years (median, 59.8 years). The defect/tongue flap dimensions ranged from 1.8 × 3.5 to 2.0 × 4.5 cm (median, 1.87 × 3.81 cm). RESULTS: No major complication developed in any patient. The postoperative esthetic results, orbicularis oris functions, and speech functions were excellent in six, eight, and nine patients, and satisfactory in five, three, and two, respectively. The patients were followed up for 13-36 months (median, 21.7 months); two local recurrences developed, and these patients underwent salvage surgeries. CONCLUSIONS: An anteriorly based ventral tongue flap is a safe and feasible option for reconstruction of lower vermilion defects.

IncRNA H19 promotes tongue squamous cell carcinoma progression through ß-catenin/GSK3ß/EMT signaling via association with EZH2.

H19 is involved in tumor metastasis and associated with tumor progression. Enhancer of zest homolog 2 (EZH2) is overexpressed in multiple cancer types and correlates with tumor proliferation, epithelial-mesenchymal transition, and poor prognosis. However, the interaction between H19 and EZH2 to promote tongue squamous cell carcinoma (TSCC) progression remains largely uncharacterized. Insitu hybridization and quantitative reverse-transcription PCR (qRT-PCR) were performed to measure H19 expression in primary TSCC and adjacent normal tissues and cell lines. EZH2 expression was determined by immunohistochemistry in matched primary TSCC and adjacent normal tissues. The correlation between H19 and EZH2 expression and clinicopathological characteristics were analyzed. The roles of H19 in cell proliferation, apoptosis, and invasion were analyzed using a H19-targeted lentivirus. Western blot and qRT-PCR were carried out to detect downstream signal pathway changes. Expression levels of downstream signaling proteins in primary TSCC tissues and adjacent normal tissues were analyzed by immunohistochemistry. H19 and EZH2 were upregulated in TSCC tissues compared to matched normal tissues, and significantly correlated with WHO grade, lymph node metastasis, and poor prognosis. H19 silencing attenuated cell proliferation, apoptosis, and invasion in vitro. H19 knockdown inhibited the activation of ß-catenin/GSK-3ß/cyclin D1/c-myc, upregulated E-cadherin and zonula occludens-1 (ZO-1), and inhibited N-cadherin, vimentin, Snail1, Twist1, and ZEB1. Silencing H19 expression also inhibited tumor progression and lung metastasis in an animal model. Our findings indicate that H19 promotes TSCC progression through association with EZH2, and affects downstream ß-Catenin/GSK3ß/EMT signaling, suggesting that H19 inhibition might be a potential target for the treatment of TSCC.

Postoperative immune response and surgical stress in selective neck dissection: Comparison between endoscopically assisted dissection and open techniques in cT1-2N0 oral squamous cell carcinoma.

BACKGROUND: Endoscopically assisted selective neck dissection (SND) has recently been applied in clinical N0 cases of oral squamous cell carcinoma (OSCC). However, nothing is known of the immune response after surgery. METHODS: A total of 60 patients with cT1-2N0 OSCC randomly underwent endoscopically assisted SND and open operations. The serum levels of IL-6, IL-8, IL-10, IL-1b, TNF-a, CRP, cortisol, ACTH, and growth hormone were analyzed before the start of the surgery (T0) and at 2 (T1), 6 (T2), 24 (T3), and 72 h (T4) after surgery. RESULTS: A total of 31 patients were randomized for endoscopic SND, whereas 29 underwent open procedures. The release of IL-6, IL-10 and CRP was significantly lower in the endoscopic group than in the open surgery group (p < 0.05), and cortisol levels were also lower in the endoscopic group (p < 0.05). CONCLUSIONS: Endoscopic SND could effectively provide lower inflammatory responses and surgical stress, reducing peri-operative trauma and accelerating recovery.

A comparative study of the endoscopy-assisted transoral approach versus external approaches for the resection of large benign parapharyngeal space tumors.

OBJECTIVE: The advantages and limitations of the endoscopy-assisted transoral approach (EATA) and external approaches (EAs) in resection of parapharyngeal space tumors (PSTs) remain unclear. In our study, we compared the use of the EATA and the EAs for the resection of large, benign PSTs. STUDY DESIGN: Forty-four patients with PSTs were divided into the EATA and EA groups. The perioperative and postoperative outcomes of the patients were evaluated. RESULTS: All of the tumors were completely removed. However, the procedure was converted to an open procedure for four patients in the EATA group and for six patients in the EA group who required endoscopic assistance. The intraoperative blood loss, amount and duration of drainage, postoperative pain, total hospital stay, and cosmetic outcomes were superior in the EATA group (P < .05). CONCLUSIONS: Use of the EATA for resection of large, benign PSTs decreased the surgical invasiveness of the procedure and resulted in better aesthetic outcomes. However, use of the combined surgical approach allowed for improved access for the resection of PSTs.

Synchronous reconstruction of bilateral osteoradionecrosis of the mandible using a single fibular osteocutaneous flap in patients with nasopharyngeal carcinoma.

BACKGROUND: The reconstruction of bilateral osteoradionecrosis (ORN) of mandibular defects using a single free bone flap is rarely performed because extensively radiated neck tissue with severe fibrosis is usually unsuitable for vascularized reconstruction. METHODS: Thirty-one patients with nasopharyngeal carcinoma (NPC) underwent bilateral reconstruction of advanced ORN in the mandible using a single fibular osteocutaneous flap. Clinical factors associated with the operation were assessed, including classification of mandible defects, types of recipient vessels, perioperative complications, and postoperative outcomes. RESULTS: All of the fibular osteocutaneous flaps survived completely, with the exception of 1 inner skin paddle that presented partial necrosis in a reconstruction of through-and-through defects. All patients experienced an improvement in cosmetic results 6 months after the reconstruction, whereas 23 patients experienced improved mouth opening compared to the preoperative condition. CONCLUSION: Advanced bilateral ORN in patients with NPC could be synchronously reconstructed with a single fibular osteocutaneous flap. © 2015 Wiley Periodicals, Inc. Head Neck 38: E-E, 2016.

miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1.

Mitochondria play an important role in the initiation of apoptosis. However, whether cisplatin can induce apoptosis by initiating a mitochondrial fission pathway and the mechanism underlying this effect remain poorly understood. In this study, we show that the mitochondrial fission protein FIS1 is upregulated upon cisplatin treatment in tongue squamous cell carcinoma (TSCC) cells. FIS1 knockdown can attenuate mitochondrial fission and cisplatin sensitivity. We found that FIS1 is a direct target of miR-483-5p and that miR-483-5p can inhibit mitochondrial fission and cisplatin sensitivity in vitro and in vivo. Furthermore, we found that miR-483-5p and FIS1 are significantly associated with cisplatin sensitivity and with overall survival in patients with TSCC in a retrospective analysis of multiple centers. This study revealed that a novel mitochondrial fission pathway composed of miR-483-5p and FIS1 regulates cisplatin sensitivity. The modulation of miR-483-5p and FIS1 levels may provide a new approach for increasing cisplatin sensitivity.

Mitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1-miR-593-5p-MFF axis.

Cisplatin has been widely employed as a cornerstone chemotherapy treatment for a wide spectrum of solid neoplasms; increasing tumor responsiveness to cisplatin has been a topic of interest for the past 30 years. Strong evidence has indicated that mitochondrial fission participates in the regulation of apoptosis in many diseases; however, whether mitochondrial fission regulates cisplatin sensitivity remains poorly understood. Here, we show that MFF mediated mitochondrial fission and apoptosis in tongue squamous cell carcinoma (TSCC) cells after cisplatin treatment and that miR-593-5p was downregulated in this process. miR-593-5p attenuated mitochondrial fission and cisplatin sensitivity by targeting the 3' untranslated region sequence of MFF and inhibiting its translation. In exploring the underlying mechanism of miR-593-5p downregulation, we observed that BRCA1 transactivated miR-593-5p expression and attenuated cisplatin sensitivity in vitro. The BRCA1-miR-593-5p-MFF axis also affected cisplatin sensitivity in vivo. Importantly, in a retrospective analysis of multiple centers, we further found that the BRCA1-miR-593-5p-MFF axis was significantly associated with cisplatin sensitivity and the survival of patients with TSCC. Together, our data reveal a model for mitochondrial fission regulation at the transcriptional and post-transcriptional levels; we also reveal a new pathway for BRCA1 in determining cisplatin sensitivity through the mitochondrial fission program.