Risk factors of post-tonsillectomy hemorrhage in adults.

OBJECTIVE: Tonsillectomy is an essential surgery and is conducted on both children and adults. However, the risk factors of post-tonsillectomy hemorrhage for adult patients remain unclear. In this study, we analyzed post-tonsillectomy hemorrhage in adult patients. METHODS: We retrospectively analyzed 325 adult patients who underwent a tonsillectomy between 2014 and 2018 in our facilities. RESULTS: The average age of this study's population was 31.7 ± 10.5 years (range: 19-70 years), and 250 (76.9%) patients were male. Overall, post-tonsillectomy hemorrhage occurred in 71 (21.8%) patients and 5 (1.5%) patients required a second surgery for hemostasis. Post-tonsillectomy hemorrhage often occurred on postoperative day zero or six. Using multiple logistic regression analysis, current smoking status (odds ratio 3.491; 95% confidence interval 1.813-6.723), male sex (odds ratio 3.924; 95% confidence interval 1.548-9.944), and perioperative non-steroidal anti-inflammatory drug administration (odds ratio 7.930; 95% confidence interval 1.004-62.64) were revealed as overall post-tonsillectomy hemorrhage risk factors. To analyze the hemorrhage period after tonsillectomy, we categorized the post-tonsillectomy hemorrhage patients into the primary (bleeding within postoperative day one) and secondary hemorrhage (bleeding on or after postoperative day two) groups. The current smoking status and older age were risk factors for primary hemorrhage and the current smoking status and sex (male) were risk factors for secondary hemorrhage. CONCLUSIONS: In this study, smoking status, sex, and perioperative non-steroidal anti-inflammatory drug administration were the clinical risk factors for adult post-tonsillectomy hemorrhage. Thus, smoking cessation is, at least, mandatory for patients who receive tonsillectomy to avoid post-tonsillectomy hemorrhage. LEVEL OF EVIDENCE: 4.

Transoral videolaryngoscopic surgery for laryngeal and hypopharyngeal cancer - Technical updates and long-term results.

OBJECTIVE: Transoral videolaryngoscopic surgery (TOVS) was developed as a non-robotic procedure for en bloc laryngo-hypopharyngeal cancer resection. Straight devices had been used for this procedure, however, some cases had difficulty to reach the lesions especially in hypopharyngeal area. To overcome this problem, technical updates to facilitate transoral manipulation were developed and long term oncological and functional results were analyzed. METHODS: Surgical indications were Tis, T1, T2 and selected T3 cases. In advanced T3 or T4 lesions, neoadjuvant chemotherapy was performed before surgery. Radiation failure cases (rT1 and rT2) were also indicated for TOVS. Resectable nodal involvement can be managed by combination of neck dissection. Ninety hypopharyngeal and 25 supraglottic cancer cases were retrospectively reviewed for survival analyses. In fresh hypopharyngeal cancer, 51 Stage 0-II disease and 32 Stage III-IV disease were included. In supraglottic cancer, 11 Stage I-II disease and 9 Stage III-IV disease were included. Twelve radiation failure cases were analyzed separately. As new devices, malleable forceps and malleable suction coagulator were introduced to reach the whole laryngo-hypopharynx. New curved blades for the FKWO retractor were developed and these were applied for difficult hypopharyngeal exposure cases by conventional blades. Swallowing functional outcome and risk factors for postoperative dysphagia were evaluated by univariate analysis. RESULTS: The 5-year overall survival, disease-specific survival and larynx preservation rate of fresh hypopharyngeal cancer cases were 83.2%, 94.3% and 94.6%, respectively. Those of supraglottic cancer cases were 80%, 95% and 94.7%, respectively. Those of salvage cases were 87.5%, 87.5% and 82.5%, respectively. Those of T3 and T4 hypopharyngeal cancer treated by neoadjuvant chemotherapy with TOVS were 75.0%, 82.5% and 100% respectively. Surgical complication included bleeding (2.6%) and emergency tracheostomy (3.4%). Oral intake was maintained in 94.8% cases. By univariate analysis, patient's age (especially 80 years of age or older), larger resected area, arytenoid resection and tracheostomy were regarded as risk factors for postoperative dysphagia. Among 31 recent cases, 5 cases had difficulty in exposing hypopharyngeal lesions by conventional blades. These exposure problems were solved by curved blades. CONCLUSION: Using malleable devices and new curved blades for the FKWO retractor, exposure problems in the hypopharynx could be solved and TOVS could be applied in more cases. Although oncological outcomes and functional outcomes were good, patients with risk factors for dysphagia should be carefully indicated.

Sentinel Lymph Node-Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model.

In clinical N0 (cN0) cases with head and neck squamous cell carcinoma (HNSCC), a treatment selection is still controversial: elective neck dissection or watchful waiting. We focused on sentinel lymph node (SLN)-targeted therapy using the urokinase-type plasminogen activator (uPA)-dependent oncolytic Sendai virus "BioKnife." The objectives of this study were to investigate BioKnife migration into SLNs and elucidate its antitumor effect on lymph node metastases (LNM). We established an orthotopic nude mouse model of HNSCC, with LNM being frequently induced. We inoculated HSC-3-M3, human highly metastatic tongue squamous cell carcinoma cells, in the tongue of the nude mice, and after 2 weeks, we injected BioKnife into the primary tumor. We tracked BioKnife migration into the SLNs by immunostaining, RT-PCR, and an in vivo imaging system. We also examined its antitumor effects and mechanisms through serial section analysis of lymph nodes. GFP reporter expression was clearly visible in the lymph nodes of virus groups, which corresponded to SLNs. Relative GFP mRNA was significantly increased in both the tongues and lymph nodes in the virus groups compared with that in the control group (P < 0.05). Serial section analysis showed that BioKnife infected cancer cells and exhibited significant antitumor effect against LNM compared with the control groups (P < 0.05). We detected apoptosis in LNM infected by BioKnife. BioKnife migrated into SLNs after its injection into the primary tumor and effectively suppressed LNM, suggesting that SLN-targeted therapy using BioKnife has great potential to provide a novel and promising alternative to elective neck dissection in cN0 patients with HNSCC.

Oncolytic Sendai virus-induced tumor-specific immunoresponses suppress "simulated metastasis" of squamous cell carcinoma in an immunocompetent mouse model.

BACKGROUND: The objectives of this study were to demonstrate anti-metastatic effect of BioKnife, uPA activity-dependent oncolytic Sendai virus, after BioKnife treatment for primary tumor, and analyze its mechanisms in a simulated metastasis mouse model of head and neck squamous cell carcinoma (HNSCC). METHODS: We established a simulated metastasis mouse model using a murine HNSCC cell line "SCCVII." We assessed a tumor size and an induction of tumor-specific immunoresponses using cytotoxic T-lymphocyte (CTL) assay, flow cytometry (FCM) in spleen and immunohistochemistry (IHC) in secondary tumor. RESULTS: Secondary tumors were significantly smaller in BioKnife-treated group. CTL activities were significantly improved in BioKnife group. FCM revealed that induction of dendritic cells and CD4+ /CD8+ lymphocytes was significantly higher in BioKnife group. IHC showed that CD8+ lymphocytes invaded secondary tumor. CONCLUSION: Tumor-specific immunoresponses induced by BioKnife has great potential to be a novel, safe, and less invasive option for control and prevention of metastasis.

Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model.

Activator protein-1 (AP-1) is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. The purpose of our study was to assess the therapeutic effects of a novel selective AP-1 inhibitor, T-5224, in preventing lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) in an orthotopic mouse model. We assessed the effect of T-5224 on HNSCC cell invasion, migration, proliferation, and MMP activity by carrying out an in vitro study using an invasion assay, scratch assay, WST-8 assay, and gelatin zymography. We also observed morphological changes in HNSCC cells by time-lapse microscopy. Furthermore, cervical lymph node metastasis was assessed using an orthotopic tumor model of human oral squamous cell carcinoma cells (HSC-3-M3) injected in the tongue of a BALB/c nude mouse. T-5224 (150 mg/kg) or vehicle was given orally every day for 4 weeks. Animals were killed and assessed for lymph node metastasis by H&E staining of resected lymph nodes. T-5224 significantly inhibited the invasion, migration, and MMP activity of HNSCC cells in a dose-dependent manner; there was no significant influence on cell proliferation. The antimetastatic effect of T-5224 was also confirmed in our animal study. The rate of cervical lymph node metastasis in the model was 40.0% in the T-5224-treated group (n = 30) versus 74.1% in the vehicle-treated group (n = 27; P < 0.05). In conclusion, T-5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph node metastasis in head and neck cancer in an animal model.

Serum midkine as a biomarker for malignancy, prognosis, and chemosensitivity in head and neck squamous cell carcinoma.

Improved therapies for individuals with head and neck squamous cell carcinoma (HNSCC) may be developed by identification of appropriate biomarkers. The aim of this study was to evaluate the usefulness of serum midkine measurement as a biomarker for HNSCC. Pretreatment serum midkine concentrations were measured in 103 patients with HNSCC and 116 control individuals by enzyme-linked immunosorbent assay. Midkine expression in tumor tissues from 33 patients with HNSCC who underwent definitive surgical resection without preoperative treatment was examined by immunohistochemistry. The cut-off serum midkine concentrations for predicting the presence of head and neck malignancy and chemosensitivity to induction chemotherapy, as determined using receiver operating characteristic curves, were 482 and 626 pg/mL, respectively. Spearman bivariate correlations showed positive correlations between serum midkine levels and immunohistochemistry staining score (r = 0.612, P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of serum midkine concentration for detection of HNSCC were 57.3, 85.3, 77.6, 69.2, and 72.1%, respectively. However, for predicting the response to induction chemotherapy, the values were 84.6, 60.9, 71.0, 77.8, and 73.5%, respectively. Serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, using Cox's proportional hazards model (P = 0.027). Overexpression of serum midkine yielded a relative risk of death of 3.77, with 95% confidence limits ranging from 1.15 to 17.0. Serum midkine levels in patients with HNSCC were associated with malignancy, chemosensitivity, and prognosis. Serum midkine may be a useful, minimally invasive biomarker for early detection, therapeutic decision-making, and predicting prognosis.

The beneficial effect of Hangesha-shin-to (TJ-014) in gentamicin-induced hair cell loss in the rat cochlea.

OBJECTIVE: Ototoxic damage caused by aminoglycosides (AG) leads to the loss of cochlear hair cells (HCs). In mammals, mature cochlear HCs are unable to regenerate, and their loss results in permanent hearing deficits. Our objective was to protect the inner ear from damage after an AG challenge. The generation of reactive oxygen species (ROS), one of the earliest events in the process of AG ototoxicity, is considered to play a key role in the initiation of HC death. We examined whether Hangesha-shin-to (TJ-014), a traditional Japanese Kampo medicine considered to be a potent antioxidant, protects HCs from gentamicin (GM)-induced damage. METHODS: Organ of Corti explants removed from postnatal day 3-5 rats were maintained in tissue culture and exposed to 50µM GM for up to 48h. The effects of TJ-014 on GM-induced ototoxicity were assessed by HC counts and immunohistochemistry against cleaved caspase-3, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and a probe reacting to mitochondrial function changes. RESULTS: TJ-014 treatments significantly reduced GM-induced HC loss and immunoreactivities for cleaved caspase-3 and 8-OHdG; these effects were correlated with increasing TJ-014 concentrations. Moreover, TJ-014 protected the mitochondrial membrane potential from GM ototoxicity. CONCLUSION: These findings indicate the potential of TJ-014 to prevent GM-induced cochlear damage involving ROS.

Risk factors for dysphagia after transoral videolaryngoscopic surgery for laryngeal and pharyngeal cancer.

BACKGROUND: Transoral surgery is gaining attention as a minimally invasive treatment option for laryngeal and pharyngeal cancer. Postoperative swallowing function is satisfactory in most cases, but occasionally dysphagia persists. METHODS: Swallowing function of 86 patients who underwent transoral videolaryngoscopic surgery (TOVS) for laryngeal and pharyngeal cancers was evaluated by the Functional Outcome Swallowing Scale (FOSS) and risk factors for dysphagia were identified. RESULTS: FOSS stage was 0 to 1 in 90%, 2 in 5.8%, 3 in 3.5%, and 4 in 1.2% of the patients. Only 1 patient had indication for percutaneous endoscopic gastrostomy (PEG). Univariate analysis revealed that resection of the pyriform sinus (p = .0280) and arytenoid (p = .0139), pulmonary dysfunction (p = .0353), and large mucosal defect (p = .0223) were associated with postoperative dysphagia. CONCLUSION: Although the rate of PEG dependency is low in transoral surgery, surgeons should mention the risk of postoperative dysphagia when counseling patients preoperatively.

Minimally invasive surgery for pyriform sinus fistula by transoral videolaryngoscopic surgery.

Pyriform sinus fistula is a rare branchial anomaly that manifests as recurrent cervical infection resulting from contamination of the fistula internal orifice in the pyriform sinus. Although open neck surgery to resect the fistula has been recommended as a definitive treatment, identifying the fistula within the scar is difficult and occasionally results in recurrence. Here, we describe a novel transoral surgical technique for pyriform sinus fistula using transoral videolaryngoscopic surgery (TOVS) as a definitive treatment to resect and close the fistula without skin incision. Needle cautery enables fine excision and delicate dissection of the fistula tract. TOVS is a safe, easy, and reliable treatment and is a suitable first line treatment.

A traditional Japanese medicine--Hangeshashinto (TJ-14)--alleviates chemoradiation-induced mucositis and improves rates of treatment completion.

PURPOSE: Oral mucositis induced by radiation or chemoradiation can cause devastating quality of life issues for patients undergoing treatment for head and neck cancer. In this study, we investigated the efficacy of a traditional Japanese medicine-Hangeshashinto (TJ-14)-for (chemo)radiation-induced oral mucositis. METHODS: Eighty patients who underwent whole neck radiation of >60 Gy with or without chemotherapy (high-dose cisplatin or low-dose docetaxel) were enrolled in this retrospective study; 40 had received TJ-14 during treatment, and 40 had not (controls). Factors related to alleviation of oral mucositis were identified by multivariate logistic regression analysis. Rates of completion of (chemo)radiation treatments were compared between the patients who received TJ-14 and the control group according to the treatment regimen. The comparison of the nutrition status between groups was also performed. RESULTS: Multivariate analysis indicated that the use of TJ-14 (p = 0.019), gender (p = 0.024), and primary tumor location (p = 0.028) were significant factors associated with the severity of oral mucositis. TJ-14 was associated with a significantly improved rate of completion of chemoradiation with cisplatin (p = 0.002). In the investigation of nutritional status, only serum albumin was significantly maintained better in the TJ-14 group than the control group in terms of mean change before and after (chemo)radiation (p = 0.024). CONCLUSIONS: The present study indicates that TJ-14 is effective for ameliorating oral mucositis induced by (chemo)radiation in patients with head and neck cancers. TJ-14 was associated with improved completion rates of chemoradiation treatments with cisplatin. A randomized controlled trial is necessary to confirm the efficacy of TJ-14 for chemoradiation-induced mucositis in head and neck cancer patients.

[Total laryngectomy using a linear stapler for laryngeal cancer].

Total laryngectomy is a well established method for the treatment of laryngeal cancer. In some cases such as elderly patients or patients with severe complications, a shorter surgical time is preferred. Total laryngectomy using a linear stapler is reportedly advantageous for shortening of the surgical time and for lowering the rate of pharyngeal fistula formation. We applied this surgical technique in three laryngeal cancer cases. After skeletonization of the larynx, the linear stapler is inserted between the larynx and the pharyngeal mucosa. Excision of the larynx and suturing of the pharyngeal mucosa are performed simultaneously. Although the number of cases is small for statistical analysis, the surgical time was shortened by about 30 minutes compared to laryngectomy with manual suturing. Total laryngectomy by linear stapler cannot be applied in all cases of advanced laryngeal cancer. However, if the tumor is confined to the endolarynx, it is a useful tool for some cases that require a shorter surgical time.

Facial baroparesis caused by scuba diving.

Middle ear barotrauma is one of the common complications of SCUBA diving representing acute otalgia, hearing loss, and bleeding. But occurrence of facial palsy is rare. Here we report a case of a 30-year-old navy diver suffered middle ear barotrauma with transient facial palsy after SCUBA diving. He felt difficulty in equalizing the pressure in middle ear with Valsalva maneuver during diving, and suffered right facial palsy and aural fullness after diving. Clinical examination showed remarkable bulging of the right tympanic membrane and right facial palsy without other neurological findings. But facial palsy was disappeared immediately after myringotomy. We considered that the etiology of this case was neuropraxia of facial nerve in middle ear caused by over pressure of middle ear.