Extranodal Natural Killer/T-cell Lymphoma, Nasal Type Occurring After Actinomyces Infection: A Case Report.

The pathogenesis of extranodal natural killer/T-cell lymphoma (ENKTL) remains largely unknown. Herein, we present a case of ENKTL that may have occurred during the treatment of Actinomyces infection. A 69-year-old woman was admitted to our hospital with nasal bleeding, and a nasopharyngeal mass was observed. The patient was diagnosed with Actinomyces infection on biopsy, and oral antibiotics were administered. The tumor decreased in size; however, swelling of the nasal mucosa and perforation of the nasal septum were observed. A biopsy revealed a recurrence of Actinomyces infection, and oral antibiotics were again administered. The mucosal swelling improved temporarily, but the condition gradually deteriorated. The patient was diagnosed with ENKTL based on a third biopsy. Retrospective evaluation of the biopsies showed that there were no CD56-positive cells in the first specimen; however, the number of CD56-positive cells gradually increased in the second and third specimens. We retrospectively observed the occurrence of ENKTL under chronic inflammatory conditions due to Actinomyces infection in this case. In addition, this case suggests that the possibility of malignancy must be considered when managing such patients with Actinomyces infection.

Taurine, Coenzyme Q10, and Hydrogen Water Prevents Germanium Dioxide-Induced Mitochondrial Dysfunction and Associated Sensorineural Hearing Loss in mouse.

Mitochondrial dysfunction has been implicated in numerous common diseases as well as aging and plays an important role in the pathogenesis of sensorineural hearing loss (SNHL). In the current study, we showed that supplementation with germanium dioxide (GeO2) in CBA/J mice resulted in SNHL due to the degeneration of the stria vascularis and spiral ganglion, which were associated with down-regulation of mitochondrial respiratory chain associated genes and up-regulation in apoptosis associated genes in the cochlea. Supplementation with taurine, coenzyme Q10, or hydrogen-rich water, attenuated the cochlear degeneration and associated SNHL induced by GeO2. These results suggest that daily supplements or consumption of antioxidants, such as taurine, coenzyme Q10, and hydrogen-rich water, may be a promising intervention to slow SNHL associated with mitochondrial dysfunction.

Assessing the usefulness of inner ear contrast-enhanced magnetic resonance imaging and pure-tone audiometry in estimating the prognostic value of hearing improvement in patients with definite Meniere's disease.

PURPOSE: Meniere's disease (MD) is characterized by combined cochlear and vestibular symptoms. However, its underlying cause remains unclear, with low-to-mid-tone hearing impairment being predominantly reported. Moreover, predicting hearing improvement after disease onset is not possible. This study aimed to assess whether hearing improvement in patients with definite MD (DMD) could be predicted using inner ear contrast magnetic resonance imaging (IEC-MRI) and pure-tone audiometry (PTA) at disease attack. MATERIALS AND METHODS: Between April 2020 and March 2022, seven outpatients with DMD were enrolled based on the Bárány Society DMD criteria. The patients were divided into two groups: low-tone hearing loss (LTL) group and low-to-mid-tone hearing loss (LMTL) group. Hearing improvement rates as well as the possible inter-relation between endolymphatic hydrops and hearing improvement were evaluated. RESULTS: Endolymphatic hydrops was found in two of four LTL cases. One of three LMTL cases had prominent lymphedema. All patients with LTL but only one patient with LMTL had hearing improvement. Endolymphatic hydrops was not found to be correlated with hearing improvement. CONCLUSIONS: Estimating hearing improvement in patients with DMD using IEC-MRI was not possible. However, PTA showed better hearing prognosis in LTL than in LMTL. Therefore, estimating hearing improvement using PTA was possible at disease attack.

Idiopathic common carotid artery laceration: A case report.

Carotid artery injury is a rare disease often caused by neck trauma or irradiation of head and neck cancer. It is not easy to diagnose quickly without these backgrounds. Herein, we report a case of a 52-year-old man with no history of trauma or irradiation whose carotid artery was found to be injured. It was suggested that patients without any other disease but hypertension could have carotid artery injury. Additionally, it was challenging to detect extravasation from the carotid artery by computed tomography scan and ultrasonography in the emergency department. We should consider the possibility of carotid artery injury when examining patients with sudden neck swelling, even without any history of trauma or irradiation.

Management of anaplastic thyroid cancer and proposed treatment guidelines-A 5-year case series study.

BACKGROUND: Anaplastic thyroid cancer is a rare and rapidly progressive cancer with an extremely poor prognosis. Besides surgical control, no clear treatment has been found, mainly due to the small population affected and high mortality rate. AIMS: To propose evidence-based treatment guidelines based on a 5-year retrospective study of patients with anaplastic thyroid cancer treated at our facility. There have been no clearly defined guidelines for treatment plan for undifferentiated thyroid cancer. Our paper presents a retrospective analysis on the treatment of patients with undifferentiated thyroid cancer at our hospital. METHODS AND RESULTS: We retrospectively evaluated the data of patients diagnosed with anaplastic thyroid cancer from April 2017 to March 2022. The total number of patients diagnosed and treated was seven. Two of these patients had operable cancer; five were inoperable and treated with lenvatinib or paclitaxel maintenance therapy. The median time from the first visit to death was 3.84 months, and six of the seven patients died before this study started. Three of them had Stage IVB cancer and died due to deterioration of their general condition, including lung metastasis; the other three had Stage IVC cancer and died of suffocation. The survivor had Stage IVB cancer, was treated by surgery combined with chemical radiotherapy, and survived >240 days. CONCLUSION: Considering the above findings, personalized surgical treatment should be prioritized to prevent suffocation. Especially in Stage IVB cancer, local control can be achieved by surgical and anticancer drug treatment to avoid death from suffocation.

Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy.

BACKGROUND: We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma. METHODS: Patients who underwent total laryngopharyngectomy at our institution between 2004 and 2014 were included in this study and retrospectively analyzed. We then discriminated for vascular invasion and lymphatic invasion of the primary tumor in all cases. RESULTS: We reviewed 135 records (120 men and 15 women; age range, 36-84 years). Tumors with lymphatic invasion tended to be associated with more metastatic lymph nodes and extracapsular spread (ECS) of metastatic lymph nodes. Tumors with vascular invasion tended to be associated with nonpyriform sinus locations. In a multivariate analysis, nonpyriform sinus locations, >3 metastatic lymph nodes, and vascular invasion remained significant prognostic factors for overall survival (OS); in recursive partitioning analysis, ECS and vascular invasion remained important categorical variables for OS. CONCLUSION: Vascular invasion is a strong prognostic biomarker for advanced hypopharyngeal carcinoma. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1535-1543, 2017.

Facial nerve paralysis associated with temporal bone masses.

OBJECTIVE: To investigate the clinical and electrophysiological features of facial nerve paralysis (FNP) due to benign temporal bone masses (TBMs) and elucidate its differences as compared with Bell's palsy. METHODS: FNP assessed by the House-Brackmann (HB) grading system and by electroneurography (ENoG) were compared retrospectively. RESULTS: We reviewed 914 patient records and identified 31 patients with FNP due to benign TBMs. Moderate FNP (HB Grades II-IV) was dominant for facial nerve schwannoma (FNS) (n=15), whereas severe FNP (Grades V and VI) was dominant for cholesteatomas (n=8) and hemangiomas (n=3). The average ENoG value was 19.8% for FNS, 15.6% for cholesteatoma, and 0% for hemangioma. Analysis of the correlation between HB grade and ENoG value for FNP due to TBMs and Bell's palsy revealed that given the same ENoG value, the corresponding HB grade was better for FNS, followed by cholesteatoma, and worst in Bell's palsy. CONCLUSIONS: Facial nerve damage caused by benign TBMs could depend on the underlying pathology. Facial movement and ENoG values did not correlate when comparing TBMs and Bell's palsy. When the HB grade is found to be unexpectedly better than the ENoG value, TBMs should be included in the differential diagnosis.

Amblyopia Associated with Congenital Facial Nerve Paralysis.

The association between congenital facial paralysis and visual development has not been thoroughly studied. Of 27 pediatric cases of congenital facial paralysis, we identified 3 patients who developed amblyopia, a visual acuity decrease caused by abnormal visual development, as comorbidity. These 3 patients had facial paralysis in the periocular region and developed amblyopia on the paralyzed side. They started treatment by wearing an eye patch immediately after diagnosis and before the critical visual developmental period; all patients responded to the treatment. Our findings suggest that the incidence of amblyopia in the cases of congenital facial paralysis, particularly the paralysis in the periocular region, is higher than that in the general pediatric population. Interestingly, 2 of the 3 patients developed anisometropic amblyopia due to the hyperopia of the affected eye, implying that the periocular facial paralysis may have affected the refraction of the eye through yet unspecified mechanisms. Therefore, the physicians who manage facial paralysis should keep this pathology in mind, and when they see pediatric patients with congenital facial paralysis involving the periocular region, they should consult an ophthalmologist as soon as possible.

Clinical Value of the Epstein-Barr Virus and p16 Status in Patients with Nasopharyngeal Carcinoma: A Single-Centre Study in Japan.

BACKGROUND: The clinical significance of the Epstein-Barr virus (EBV) status and p16 expression was unknown in nasopharyngeal carcinoma (NPC). METHODS: We retrospectively studied our pathology database for 13 years to determine the prevalence of EBV and p16 expression and their association with prognosis in cases of NPC. We performed immunohistochemistry for the p16 protein and in situ hybridization (ISH) for EBV-encoded small RNAs and human papillomavirus (HPV) DNA. RESULTS: Of the 43 patients with NPC, 27 (63%), 6 (14%), and 10 (23%) cases were EBV positive, EBV negative with keratinization, and EBV negative without keratinization, respectively. No cases were HPV positive by ISH. Among the 21 EBV-positive tumours that were tested for p16, only 2 tumours were p16 positive. The keratinization-positive group included only males, typically >60 years of age (5 of 6) and with T4 tumours (3 of 6). In contrast, the EBV-positive cohort tended to be younger (<60 years, 13 of 27) and have progressive N-stage tumours (N2-3, 14 of 27). The keratinization and EBV-negative cohort included predominantly males (9 of 10) who were likely p16 negative (4 of 10) and smokers (7 of 10). Multivariate analysis confirmed that keratinization was an independent prognostic factor for progression-free survival. CONCLUSION: In areas, such as Japan, that are nonendemic for both EBV and HPV, the causality of NPC appears to be more heterogeneous.

Induction Chemotherapy for p16 Positive Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: We aimed to determine the effectiveness of induction chemotherapy for treating p16-positive oropharyngeal cancer in our department. STUDY DESIGN: This was a retrospective case series to assess treatment effectiveness. METHODS: We administered induction chemotherapy to patients with stage III to IV oropharyngeal p16-positive squamous cell carcinoma between 2008 and 2013. Induction chemotherapy was administered using combinations of docetaxel, cisplatin, and 5-fluorouracil. We measured the survival rates using the Kaplan-Meier method and log-rank test. RESULTS: We reviewed 23 patients (18 men and 5 women; age, 42-79 years). Induction chemotherapy resulted in partial or complete remission (20 patients) and in stable (2 patients) or progressive (1 patient) disease. In partial or complete remission, subsequent radiotherapy was performed in 16 patients, chemoradiotherapy in two, and transoral resection in two. In stable or progressive disease, subsequent open surgery was performed. Overall, one patient died of cervical lymph node metastasis, one died of kidney cancer, and one died of myocardial infarction. Event-free, distant-metastasis-free survival was present for 20 patients. The 3-year disease-specific survival was 95%; the overall survival was 87%. Two patients required gastrostomies during chemoradiotherapy and three required tracheotomies, but these were closed in all patients. CONCLUSION: The therapeutic response to induction chemotherapy for p16-positive oropharyngeal cancer was good. Partial or complete remission was achieved in almost 90% patients, and control of local and distant metastases was possible when it was followed by radiotherapy alone or with transoral resection of the primary tumor. A multicenter study is required to confirm these findings. LEVEL OF EVIDENCE: 4.

Ninety-day oral toxicity study of rhamsan gum, a natural food thickener produced from Sphingomonas ATCC 31961, in Crl:CD(SD)IGS rats.

This study was designed to evaluate and characterize any subchronic toxicity of rhamsan gum, a polysaccharide produced from Sphingomonas strain ATCC 31961, when administered to both sexes of Crl:CD(SD)IGS rats at dietary levels of 0 (control), 0.5, 1.5, and 5.0% (10 rats/sex/group). During the study, the treatment had no adverse effects on clinical signs, survival, body weights and food and water consumption, or on findings of urinalysis, ophthalmology, hematology, or blood biochemistry. Examination of gross pathology and histopathology exhibited no differences of toxicological significance between control and treated rats. Increased relative cecum (filled) and cecum (empty) weights, evident in males of 1.5% group and both sexes of the 5.0% group, were considered to be a physiological adaptation. Thus, the results indicated the toxic level of rhamsan gum to be more than 5.0%, and the no-observed-adverse-effect level (NOAEL) was concluded to be 5.0% (3,362 mg/kg body weights/day for males, and 4,304 mg/kg body weights/day for males) from the present study.

A 90-day oral toxicity study of nisin A, an anti-microbial peptide derived from Lactococcus lactis subsp. lactis, in F344 rats.

This study was designed to evaluate and characterize any adverse effect of nisin A, when administered to both sexes of F344/DuCrlCrlj rats (10 males and 10 females in each group) at dietary levels of 0%, 0.2%, 1.0% and 5.0% for 90 days. Animals given NaCl at a dietary level of 3.712% (equivalent to the NaCl content in 5.0% nisin A diet) served as a reference material treated group. There were no deaths, and the treatment had no toxicologically significant effects on clinical signs, body weights, food consumption, ophthalmology, hematology, or gross pathology. Statistically significant increases of water consumption, urine volume, and urinary sodium and chlorine, and decreases of urinary potassium and serum sodium, along with increases of absolute and relative kidney weight, and incidences of minimal squamous cell hyperplasia of limiting ridge in the forestomach, were found in nisin A-treated groups. It was considered that these changes were related to NaCl, since they were also noted in rats given diet containing the reference substance. Thus, no toxicologically significant changes were apparent in both sexes of F344/DuCrlCrlj rats fed diet containing 0%, 0.2%, 1.0% and 5.0% nisin A for 90 days. Therefore, the no-observed-adverse-effect level (NOAEL) for nisin A was concluded to be a dietary level of 5.0% (2996 mg/kg/day for males and 3187 mg/kg/day for females).

A 28-day oral toxicity study of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, in F344 rats.

This study was designed to evaluate any adverse effect of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, when administered to both sexes of F344 rats at dietary levels of 0, 1.25, 2.5, and 5.0% for 28 days. The treatment had no adverse effects on clinical signs, mortality, body weights and food and water consumption, or on urinalysis, ophthalmology, hematology, blood biochemistry, and histopathology findings. At necropsy, slight increased absolute and relative cecum weights, evident in females ingesting 2.5% and 5.0% dietary levels, were considered to be a physiological adaptation to the poorly absorbed fermentation-derived cellulose. The non-observed-adverse-effect level (NOAEL) from the present study was concluded to be 5.0% in the diet (5,331 mg/kg body weights/day for males, and 5,230 mg/kg body weights/day for females).

A twenty eight-day repeated dose toxicity study of black soybean extract in Sprague-Dawley rats.

This study was designed to evaluate any adverse effect of a hot water extract of black soybeans (Glycine max (L.) Merr.), when administered to both sexes of Crj:CD(SD)IGS rats at dietary levels of 0 (control), 0.5, 1.5 and 5.0% (6 rats/sex/group). During the study, the treatment had no adverse effects on clinical signs, survival, body weights, and food and water consumption, or on findings of ophthalmology, urinalysis, hematology, or blood biochemistry. Organ weights, gross pathology and histopathology exhibited no differences of toxicological significance between control and treated rats. Thus, the no-observed-adverse-effect level (NOAEL) of black soybean extract was concluded to be 5.0% (3,618 mg/kg body weight/day for males and 4,066 mg/kg body weight/day for females) from the present study.

Mutation and overexpression of the transgene in ethylnitrosourea-induced tumors in mice carrying a human prototype c-Ha-ras gene.

To investigate mechanisms underlying accelerated carcinogenesis in mice carrying a human prototype c-Ha-ras gene (rasH2 mouse), mutations and the expression profile of the transgene were evaluated in 14 tumors induced by a single injection of ethylnitrosourea (ENU), with or without additional beta-estradiol 3-benzoate (EB) treatment. Although no codon 12 mutations were detected, changes in codon 61 were evident in all lung adenocarcinomas, skin squamous cell carcinomas and forestomach squamous cell carcinomas examined. The mRNA levels of the transgene in these lesions were also elevated 1.71- to 4.77-fold, 3.04- to 5.18-fold, and 3.00- to 5.67-fold, respectively, in comparison with those in the normal livers of rasH2 mice. The results obtained in this study suggest that mutations in codon 61 and amplification of the transgene play key roles in the carcinogenesis induced by ENU in rasH2 mice.

Absence of liver tumor promoting effects of annatto extract (norbixin), a natural carotenoid food color, in a medium-term liver carcinogenesis bioassay using male F344 rats.

Modifying potential of annatto extract (norbixin) on liver carcinogenesis was investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given annatto extract at dietary levels of 0, 0.03, 0.1 and 0.3%, or phenobarbital sodium at 0.05% as a positive control for 6 weeks. All animals were subjected to partial hepatectomy at week 3, and were killed at week 8. There were no deaths related to annatto extract ingestion, and the treatment had no effects on body weights, or food and water consumption. Statistically significant increases of absolute and relative liver weights were apparent in the 0.1 and 0.3% groups. However, annatto extract did not significantly increase the quantitative values for glutathione S-transferase placental form positive liver cell foci observed after DEN initiation, in clear contrast to the positive control case. The results thus demonstrate that annatto extract at a dietary level of 0.3% (200 mg/kg/day) lacks modifying potential for liver carcinogenesis in our medium-term bioassay system.

Mutation analysis of vinyl carbamate or urethane induced lung tumors in rasH2 transgenic mice.

Previous studies showed that significant differences in mutation frequency of the human c-Ha-ras transgene between vinyl carbamate (VC)- and ethyl carbamate (urethane)-induced lung tumors were observed in rasH2 mice. It remains unclear why the point mutation frequency is extremely low in VC-induced lung tumors, although this compound is much more carcinogenic than urethane. In this study, we examined the somatic point mutations of the transgene at the RNA level in VC- and urethane-induced lung tumors of rasH2 mice. We did not find any mutation at codon 12 of the transgene in any of these lung tumors, but codon 61 showed frequent mutations in not only urethane-induced lung tumors (15 out of 16) but also VC-induced lung tumors (11 out of 11) in rasH2 mice. These results suggested that point mutations at codon 61 of the transgene play an important role in the carcinogenesis of VC- and urethane- induced lung tumors in rasH2 mice.

Dose-threshold for thyroid tumor-promoting effects of xylazine in rats.

To clarify the threshold dose of thyroid tumor-promoting effects of xylazine hydrochloride (XZ), male F344 rats received pulverized basal diet containing 0, 250, 500, or 1000 ppm XZ for 26 weeks with or without initiation of 2400 mg/kg N-bis(2-hydroxypropyl)nitrosamine (DHPN). Thyroid weights significantly increased in the groups with or without DHPN initiation that were given 500 ppm XZ or more. The serum thyroxine (T4) and triiodothyronine (T3) levels decreased significantly in the XZ 250 and XZ 1000 ppm groups, respectively, although there were no remarkable changes in the serum thyroid-stimulating hormone (TSH) levels. Histopathologically, follicular cell hyperplasias and adenomas were induced in the DHPN-alone and DHPN+XZ groups, and the incidences and multiplicities of these lesions in the DHPN groups treated with 500 ppm XZ or more were significantly higher than those in the DHPN alone group. These results suggest that the threshold dose of rat thyroid tumor-promoting effects of XZ is between 250 and 500 ppm under the present experimental condition.

Lack of susceptibility of heterozygous p53-knockout CBA and CIEA mice to phenolphthalein in a 6-month carcinogenicity study.

Phenolphthalein has carcinogenic activity, causing malignant lymphomas in B6C3F1 mice at a dietary dose of 3000 ppm in a 2-year carcinogenicity study and in female heterozygous p53-knockout TSG mice (C57BL/6 background) at the same dose in a 6-month study. To examine whether carcinogenic potential of phenolphthalein can be detected in other p53-knockout mouse [p53 (+/-)] strains such as p53 (+/-) CBA mice or p53 (+/-) CIEA mice (C57BL/6 background) and their littermates, they were given a diet containing 0, 6000 or 12000 ppm for 6 months. Unequivocal induction of neoplastic lesions was not apparent, suggesting that p53 (+/-) CBA mice and p53 (+/-) CIEA mice are resistant to the induction of malignant lymphomas by the treatment of phenolphthalein.