Case Report: Solid variant of papillary thyroid carcinoma in a young adult with Turner syndrome with chronic thyroiditis.

Turner syndrome is associated with an increased risk of developing several neoplasms. In particular, a clinical feature of Turner syndrome with chronic thyroiditis implies a relationship with thyroid malignancies. We report a very rare case of a solid variant of papillary thyroid carcinoma that was identified during a follow-up of chronic thyroiditis in a 22-year-old woman with Turner syndrome. The patient had no notable history of radiation exposure. No genetic mutations relating to the occurrence of the solid variant of papillary thyroid carcinoma, including RET/PTC rearrangements and mutations in the BRAF or RAS, were detected by a gene panel test, namely, the Oncomine™ Dx Target test. To the best of our knowledge, this is the first report of a solid variant of papillary thyroid carcinoma in a young adult with Turner syndrome with chronic thyroiditis. Our case suggests that in patients with Turner syndrome, there may be different pathogeneses from those previously reported, including exposure to radiation or known genetic mutations for the development of a solid variant of papillary thyroid carcinoma.

Chondroma Arising from the Temporomandibular Joint: A Case Report.

Periarticular chondromas are common in the humerus and femur but rarely occur in the temporomandibular joint. We report a case of a chondroma in the anterior part of the ear. One year prior to his visit, a 53-year-old man became aware of swelling in the right cheek region which gradually increased in size. In the anterior part of the right ear, there was a palpable 25 mm tumor, elastic and hard, with poor mobility and without tenderness. A contrast-enhanced computed tomography CT showed a mass lesion with diffuse calcification or ossification in the upper pole of the parotid gland and areas of poor contrast within. A magnetic resonance imaging showed a low-signal mass lesion at the parotid gland with some high signals in both T1 and T2. Fine-needle aspiration cytology did not lead to diagnosis. Using a nerve monitoring system, the tumor was resected with normal tissue of the upper pole of the parotid gland in the same way as for a benign parotid tumor. Distinguishing between pleomorphic adenoma, including diffuse microcalcification of the parotid gland and cartilaginous tumors of the temporomandibular joint, may be sometimes difficult. In such cases, surgical resection may be a beneficial treatment option.

Reliable and safe salivary duct repositioning technique with partial transection and intraductal stenting: Technical notes.

Salivary duct repositioning is often performed after excision of malignant tumors or removal of sialoliths to maintain salivary function and minimize the risk of swelling or pain due to the obstruction of the gland. However, there is risk of intraoperative tissue damage due to traumatic manipulation, leading to stenosis; in addition, the small diameter of the duct also renders this procedure difficult. Recently, we improved our method of salivary duct repositioning as follows. In the first technique, partial transection is made on the lateral wall of the duct ligated with thread at the end. Pulling the thread provides a view of the lumen, and appropriate tension enables a reliable and non-invasive procedure without requiring the operator to grasp the edge of the duct directly. When the diameter of the duct is small, intraductal stenting, the second technique, can be combined with the former technique by probe insertion to expand the lumen. Our approach is technically easy and simple which can be accepted by any clinicians and it could also be a promising technique that can serve as a less invasive and effective treatment.

A rare case of Pseudomonas aeruginosa enteritis induced by pembrolizumab.

A 72-year-old male had pseudomonal enteritis related to pembrolizumab. Chemotherapy for hypopharyngeal carcinoma with lung metastasis comprised cisplatin, 5-FU, and pembrolizumab. On day 14 of chemotherapy treatment he had a sudden prominent abdominal bulge, decreased consciousness, and drop in blood pressure in septic shock. CT scan showed marked intestinal gas through to intrahepatic bile ducts. Pseudomonas aeruginosa was simultaneously detected in both blood and stool cultures. Intestinal endoscopy revealed ulcerative lesions from the transverse colon to the rectum. Pathological investigations indicated apoptosis of the villus. The patient was diagnosed with pseudomonal enteritis induced by immune-related adverse events from the use of pembrolizumab. Treatment by corticosteroid and meropenem were subsequently switched to cefepime and metronidazole, and this successfully improved his colitis. In this new era of biological-targeted drugs and as clinical experience grows, we recommend a high level of alertness for potential diagnosis of infectious complications.

Respiratory quinolones can eradicate amoxicillin-induced mature biofilms and nontypeable Haemophilus influenzae in biofilms.

OBJECTIVES: Biofilm is thought to be involved in the persistent bacterial infections caused by nontypeable Haemophilus influenzae (NTHi). This study aims to evaluate the efficacy of antibiotics against NTHi biofilms. METHODS: A 96-wells pin replicator assay was applied for evaluation of antimicrobial efficacies against NTHi biofilms. The NTHi IH-202 strain for the standard and 10 clinical strains were evaluated, as well as the viability of NTHi in biofilms after antimicrobial exposures. RESULTS: Biofilms formed by IH-202 strain accumulated during incubation. AMPC if not high concentrations, neither reduce or inhibit biofilm formation, nor eradicate matured NTHi biofilms. The NTHi in matured biofilm were alive after exposure to amoxicillin (AMPC). Even high concentration of AMPC produced live NTHi after suspension of exposure, while tosufloxacin and garenoxacin inhibited biofilm formation of NTHi and eradicated matured biofilms. The respiratory quinolones, but not AMPC, killed NTHi in biofilms even at sub-MIC. CONCLUSIONS: NTHi persists in biofilms, even after exposure to AMPC. These findings may eventually lead to a better understanding of effective use of antibiotics to eradicate NTHi growing as biofilms, or even to the development of novel therapeutic agents for treating patients with mucosal NTHi biofilm infections. Meanwhile, respiratory quinolones are attractive agents in reducing NTHi biofilm formation and destroying established biofilm.

Lateral approach contributes to shortened surgical time in video-assisted neck surgery (VANS) for thyroid nodule.

Background: Despite endoscopic thyroid surgery contributing to excellent cosmetic outcomes, it requires longer surgical time than open surgery. This study evaluates the factors associated with operative time in video-assisted neck surgery. Methods: We retrospectively reviewed patients who underwent hemithyroidectomy by video-assisted neck surgery at a single hospital between 2017 and 2021. The clinical parameters were evaluated: age, sex, body weight, body mass index, coexistence of Hashimoto thyroiditis, side of operation, surgical approach to thyroid (midline approach or lateral approach), operation time, amount of blood loss during surgery, maximum tumor diameter and tumor volume, and postoperative complications. These parameters were compared to investigate the association of operative time and surgical approach. Results: Seventy consecutive patients were enrolled in this study, the median age at operation was 50 years, and there were 6 (8.6%) men and 64 (91.4%) women. The median body weight and body mass index at operation were 56.6 kg and 21.5, respectively. Coexistence of Hashimoto thyroiditis was found in 17 (24.3%) patients. Significant differences were found between the groups with longer and shorter operation time than median 201 minutes in surgical approaches to the thyroid (P < .001) and the amount of bleeding during surgery (P = .039). There were no differences in other candidates between the groups. Median operation times were 242 minutes in midline approach and 131 minutes in lateral approach (P < .001). Conclusion: The lateral approach of video-assisted neck surgery to the thyroid can contribute to shortened surgical time in the case of benign thyroid nodules.

A case of concurrent occurrence of carcinoma showing thymus-like differentiation and follicular variant of papillary thyroid cancer in the same thyroid.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare thyroid cancer. This is the first report of a case of concurrent occurrence of CASTLE with papillary thyroid carcinoma (PTC). A 66-year-old male patient had hoarseness with right vocal cord paralysis. Ultrasonography revealed a hypoechoic nodule in the inferior pole of the right thyroid lobe. Ultrasound-guided fine-needle aspiration cytology suggested differentiated thyroid cancer. The patient underwent total thyroidectomy with neck dissection. Pathological examination revealed two different thyroid cancers: a CASTLE and a follicular variant of PTC. Postoperative radiation therapy was performed. The patient was still alive after 5 year following the initial treatment without evidence of recurrence. The oncological management of patients with concurrent occurrence of different thyroid cancers should consider the biological behavior of both tumors.

Pharyngolaryngectomy with thoracoscopic esophagectomy via the left thoracic approach for cervical esophageal cancer with right aortic arch: Case report.

We performed pharyngolaryngectomy with thoracoscopic esophagectomy via the left thoracic approach and reconstruction of the elongated gastric conduit with microvascular anastomosis for an 83-year-old male patient with esophageal cancer and right aortic arch. For such cases, a surgical approach via the left thoracic cavity is rational, and cases of pharyngolaryngectomy with thoracoscopic esophagectomy require a long reconstruction organ. Also, in cases of right aortic arch, a longer reconstruction route is made to avoid Kommerell's diverticulum. The patient had laryngeal cancer and was diagnosed with cervical esophageal cancer and preoperative computed tomography revealed right aortic arch. There were no complications after surgery, and food intake was good. Pharyngolaryngectomy with thoracoscopic esophagectomy via the left thoracic approach and reconstruction of the elongated gastric conduit with microvascular anastomosis is suggested to be a safe and feasible technique for cases of cervical esophageal cancer with right aortic arch.

Impact of the practical guideline on appropriate usage of antimicrobial treatments for surgical site infections in reconstructive surgery of head and neck cancer.

OBJECTIVES: In 2016, Japanese Society of Chemotherapy and Japan Society for Surgical Infection presented the practical guideline for appropriate usage of antimicrobial agents to prevent postoperative infections. This study aims to exhibit the validity of the guideline as a series of effective strategies for prevention of surgical site infections (SSIs) during reconstructive surgery of the head and neck cancer. METHODS: We retrospectively evaluated patients who underwent head and neck reconstructive surgery with free or pedicle flaps in a single institute in Japan between July 2010 and July 2020. We evaluated the incidence of SSIs, patient backgrounds, and microbiological characteristics on the basis of antimicrobial prophylaxis recommended by the guideline. RESULTS: Enrolled in this study were 102 patients in our institution who underwent head and neck reconstructive surgery with free or pedicle flaps between July 2010 and July 2020. In the period between January 2018 to July 2020 after the SSI guideline was advocated (SSI guideline period), the ratio of administration of sulbactam/ampicillin (SBT/ABPC) was significantly higher (P < 0.001) and the duration of prophylactic antimicrobial treatment was significantly shorter than in the period between July 2010 to December 2017 before the SSI guideline was advocated (Pre-SSI guideline period) (P < 0.001). Incidence of SSIs were similar, even when antibiotic use was changed to be short-term single-agent administration in accordance with the practical guideline. CONCLUSIONS: Adherence to the current Japanese practical guideline on appropriate antimicrobial prophylaxis for SSIs can shorten the duration of usage of antimicrobial treatment without increasing the risk for occurrence of SSIs.

Starplasty contributes to reduce tracheostomal granulation in pediatric tracheostomy.

BACKGROUND: Starplasty tracheostomy for pediatric patients has been suggested to reduce complications, including accidental decannulation and granulation. OBJECTIVES: This study, based in a single hospital, aims to evaluate whether starplasty tracheostomy decreases the incidence of postoperative granulation of tracheostoma. MATERIAL AND METHODS: A retrospective review was performed of patients that underwent tracheostomy under the age of 10 years in a single center between January 2001 and August 2020. RESULTS: Of the 46 patients reviewed, 18 were males and 28 were females, and the median age at the initial operation was 6 months. Methods of tracheostomy were starplasty in 16 patients, vertical in 15 patients, horizontal H-shaped in 10 patients, fenestration in 3 patients, and trap door/inverted U-shaped in two patients. During observation, tracheostoma granulation was found in 25 patients and bleeding from tracheostoma occurred in one patient. No other major complications were observed. The incidence of postoperative tracheostoma granulation was significantly lower in patients that underwent starplasty tracheostomy compared with patients that underwent other types of tracheostomy (p = .007). There was no difference in survival outcomes or ratio of decannulations. CONCLUSIONS: Starplasty tracheostomy was shown to decrease the incidence of tracheostoma granulation compared with other types of tracheostomy.

Cancer Stem Cells in Oropharyngeal Cancer.

Oropharyngeal cancer (OPC), which is a common type of head and neck squamous cell carcinoma (HNSCC), is associated with tobacco and alcohol use, and human papillomavirus (HPV) infection. Underlying mechanisms and as a result prognosis of the HPV-positive and HPV-negative OPC patients are different. Like stem cells, the ability of self-renewal and differentiate, cancer stem cells (CSCs) have roles in tumor invasion, metastasis, drug resistance, and recurrence after therapy. Research revealed their roles to some extent in all of these processes but there are still many unresolved points to connect to CSC-targeted therapy. In this review, we will focus on what we currently know about CSCs of OPC and limitations of our current knowledge. We will present perspectives that will broaden our understanding and recent literature which may connect to therapy.

A Rare Case of Thyroid Carcinoma Showing Thymus-Like Differentiation in a Young Adult.

Thyroid carcinoma showing thymus-like differentiation (CASTLE) is thought to originate from ectopic thymic tissue or remnants of the developing thymus within or adjacent to the thyroid. This case report describes a mass located on the left thyroid of a 28-year-old man. Fine-needle aspiration cytology revealed a number of lymphoid cells without atypia that were similar to those seen in a malignant lymphoma of the thyroid, and surgery was performed. Based on additional histopathological findings, the tumor was finally diagnosed as a CASTLE. It is difficult to diagnose this neoplasm using fine-needle aspiration cytology. However, it is possible to differentially diagnose CASTLE based on its histological features. CD5 is useful for diagnosing CASTLE with immunohistochemical staining.

Synergistic Effects of Lenvatinib (E7080) and MEK Inhibitors against Anaplastic Thyroid Cancer in Preclinical Models.

E7080, known as lenvatinib, is an oral multitargeted tyrosine kinase inhibitor that has been shown to improve the survival rate of patients with radioiodine-refractory thyroid cancer. However, a majority of patients do not continue lenvatinib intake due to disease progression or significant toxicity. To improve treatment success rates, we propose the combination of lenvatinib with mitogen-activated protein kinase (MEK) inhibitors. To test this hypothesis, we tested the effects of lenvatinib with the MEK inhibitor U0126 in vitro using two human anaplastic thyroid cancer (ATC) cell lines, 8505C and TCO1, and with another MEK inhibitor, selumetinib (AZD6244), in an ATC mouse model. We found that the combination of lenvatinib with MEK inhibitors enhanced the antitumor effects of monotherapy with either agent in vitro and in vivo, and these effects may be through the AKT (Protein Kinase B) and extracellular signal-regulated kinase (ERK) signaling pathways. Furthermore, the combination does not have significant adverse effects in the ATC mouse models in terms of body weight, blood biochemical parameters, and histopathology. In conclusion, the combination of lenvatinib with an MEK inhibitor is a potentially viable therapeutic approach for ATC treatment.

A case report of synchronous bilateral tonsillar carcinoma associated with human papilloma virus.

The case of a 69-year-old man with bilateral synchronous tonsillar carcinoma is reported. The patient complained of nasal closure, strange voice, and discomfort in his pharynx when he was admitted to the Department of Otolaryngology Head and Neck Surgery at Wakayama Medical University, Wakayama, Japan, in March 2017. The palatine tonsils were enlarged and the surface was irregular. Left cervical lymphadenopathy was also evident. Histological examination from both tonsils was performed and bilateral tonsillar squamous cell carcinoma was diagnosed. PCR analysis showed the same HPV-DNA pattern from bilateral tonsils. Concurrent chemoradiotherapy was performed. Total 70 Gy of irradiation (2Gy/day×35 day) was applied to bilateral tonsillar tumours and upper neck. Follow up was conducted every three months and the patient was free of recurrence for three years. Patient's informed consent was taken to publish the case report.

MicroRNA 200b promotes mesenchymal-to-epithelial transition in anaplastic thyroid carcinoma.

Anaplastic thyroid cancer (ATC) remains a cancer with one of the worst prognoses, despite novel targeted therapies. The median survival rate has not improved for decades. Epithelial-to-mesenchymal transition (EMT) is a crucial step in physiological processes and in cancer progression, but the underlying mechanisms are not yet fully understood. The current study examined the role of microRNA (miR)-200b in mesenchymal-to-epithelial transition in ATC. Total RNA and miR isolation were performed from ATC cell lines transfected with a miR-200b mimic. After miR-200b mimic transfection, expression levels of E-cadherin, vimentin and zinc finger E-box binding homeobox 1 (ZEB1) were confirmed by reverse transcription-quantitative PCR and western blotting. Additionally, cell migration was evaluated using miR-200b mimic and scrambled negative control-transfected cells. A total of 14 human ATC and 15 non-cancerous human thyroid tissues were immunohistochemically stained and scored as controls for E-cadherin, vimentin and ZEB1. In ATC tissues and cell lines, the mesenchymal marker ZEB1 was significantly upregulated and the epithelial marker E-cadherin was significantly downregulated. Additionally, the mesenchymal marker vimentin was significantly upregulated in ATC tissues and in one ATC cell line. MiR-200b mimic transfection significantly increased vimentin and ZEB1 expression, but E-cadherin expression remained below the measurement sensitivity. Furthermore, miR-200b overexpression decreased cell migration. The current study suggested that miR-200b may regulate the expression levels of mesenchymal markers such as vimentin and ZEB1 in ATC and may promote mesenchymal-to-epithelial transition.

Subjective Loudness Using External Noise Reflects the Loudness and Distress of Tinnitus: A Cross-Sectional Study.

OBJECTIVES: Subjective tinnitus loudness has been measured using loudness matches, which compare tinnitus loudness with pure tones from an audiometer. When patients compare the sound pressure of certain noises with the tinnitus loudness, however, there may be remarkable differences from the measurements according to loudness matches. Subjective loudness (SubL) is an estimation of the sound pressure of tinnitus loudness by comparison of noises considered to be most similar to tinnitus loudness of patient. We examine whether SubL is inferior to loudness matches in measurement of subjective tinnitus loudness. DESIGN: Single-group cross-sectional study. PATIENTS: Included in this study were a clinical group of 111 patients with the chief complaint of subjective tinnitus. Seven of the 111 patients were excluded due to missing audiometry or questionnaire data. METHODS: Patients assessed the tinnitus loudness and related distress using visual analogue scales (VAS-L and VAS-S) and answered the Tinnitus Handicap Inventory (THI). Hearing acuity, tinnitus pitch, and loudness were then measured using an audiometer. RESULTS: VAS-L, VAS-S, and THI scores significantly correlated with loudness match using Goodwin's method (SL2) and SubL. Subgroup analysis based on patient ages indicated that all correlations of SL2 with VAS-L, VAS-S, and THI scores were no longer seen in patients more than 60 years of age. Meanwhile, SubL correlated with VAS-L, VAS-S, and THI scores in all subgroups. CONCLUSIONS: SubL was a good reflection of self-reported loudness and distress of tinnitus. It may therefore be a simple and easy means of assessing tinnitus loudness and associated distress during pre-examination without an audiometer.

A rare case of the recurrent surgery for cribriform-morular variant of papillary thyroid carcinoma.

INTRODUCTION: The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is an uncommon subtype of PTC, and it is associated with familial adenomatous polyposis (FAP). PRESENTATION OF CASE: We describe a 32-year-old female who presented recurrent CMV-PTC with FAP. Surgery performed after the recurrent disease resulted in left recurrent laryngeal nerve palsy due to formation of strong scar after initial operation. The histopathological examination revealed the recurrent CMV-PTC without thyroid capsular invasion in remnant thyroid tissue of berry ligament. In addition, the immunohistochemical analysis showed that ß-Catenin was diffusely positive in both cytoplasm and nucleus in CMV-PTC tissue. CONCLUSION: Total thyroidectomy in CMV-PTC with FAP should be performed at initial surgery due to high recurrence.

Identification and chemoresistance of cancer stem cells in HPV-negative oropharyngeal cancer.

The underlying mechanisms of resistance to chemoradiotherapy of human papilloma virus (HPV)-negative patients with oropharyngeal cancer (OPC) remain unclear. The present study aimed to characterize cancer stem cells (CSC) of the HPV-negative OPC cell line in terms of chemotherapy resistance. CSCs were isolated through magnetic activated cell sorting using the CSC specific marker aldehyde dehydrogenase 1 antibody, and characterized by sphere formation capacity, immunofluorescence staining, and CSC marker expression. CSC response to cisplatin treatment was evaluated via XTT-assays. Spheres of CSCs of the HPV-negative UTSCC-60A cell line were highly dark holospheres. RNA expression levels of CSC markers OCT4, SOX2, Kruppel-like factor 4 and BMI1 were significantly higher in CSC. CSCs were significantly resistant to cisplatin treatment at various dosages compared with nonCSC. The present study suggested that the proportion of CSCs is very low in the tumor bulk, CSCs are resistant to cisplatin in HPV-negative OPC, which requires further investigation to define their mechanism.

A novel therapeutic approach for anaplastic thyroid cancer through inhibition of LAT1.

A novel therapeutic approach is urgently needed for patients with anaplastic thyroid cancer (ATC) due to its fatal and rapid progress. We recently reported that ATC highly expressed MYC protein and blocking of MYC through its selective inhibitor, JQ1, decreased ATC growth and improved survival in preclinical models. One of the important roles of MYC is regulation of L-neutral amino acid transporter 1 (LAT1) protein and inhibition of LAT1 would provide similar anti-tumor effect. We first identified that while the human ATC expresses LAT1 protein, it is little or not detected in non-cancerous thyroidal tissue, further supporting LAT1 as a good target. Then we evaluated the efficacy of JPH203, a LAT1 inhibitor, against ATC by using the in vitro cell-based studies and in vivo xenograft model bearing human ATC cells. JPH203 markedly inhibited proliferation of three ATC cell lines through suppression of mTOR signals and blocked cell cycle progression from the G0/G1 phase to the S phase. The tumor growth inhibition and decrease in size by JPH203 via inhibition of mTOR signaling and G0/G1 cell cycle associated proteins were further confirmed in xenograft models. These preclinical findings suggest that LAT1 inhibitors are strong candidates to control ATC, for which current treatment options are highly limited.

Recurrent bacterial translocation from gut and sepsis in Head and neck cancer patients and its prevention by probiotics.

Head and neck cancers are the 6th most common cancer type in human malignant tumors and treated with chemoradiotherapy and surgery. Chemotherapy during these treatment modalities leads to damage of intestinal epithelial barriers and results in translocation of intestinal bacteria in bloodstream through invasion in these damaged regions. In this report, we report two cases of hypopharyngeal cancer patients, both of whom received chemotherapy before surgery. The patients demonstrated repeated sepsis before and after surgery, supporting translocation of intestinal bacteria. Proper continuous probiotic use prevented proliferation and intestinal bacterial translocation. Hypothesis of bacterial translocation and prevention by probiotics are discussed.