Maoto, a traditional herbal medicine, for post-exposure prophylaxis for Japanese healthcare workers exposed to COVID-19: A single center study.

BACKGROUND: Little research has been done on post-exposure prophylaxis (PEP) for COVID-19. This study was done to determine if maoto, a traditional herbal medicine commonly used for diseases with symptoms similar to those of COVID-19, can be repurposed for post-exposure prophylaxis to prevent the spread of nosocomial infection with SARS-CoV-2. METHODS: A cohort analysis was done of the data of 55 health care workers (HCWs) whether to get infected with SARS-CoV-2 in a Japanese hospital experiencing a COVID-19 cluster in April of 2021. Of these subjects, maoto granules for medical use were prescribed for PEP to 42 HCWs and taken for three days in mid-April. Controls were 13 HCWs who rejected the use of maoto. Polymerase chain reaction was performed routinely once or twice a week or when a participant presented with symptoms of COVID-19. RESULT: There were no background differences between the maoto and control groups by profession, sex, or mean age. No severe adverse reactions were observed. During the observation period of 1 week, significantly fewer subjects were diagnosed with COVID-19 in the maoto group (N = 3, 7.1%) than in the control group (N = 6, 46.2%). The prophylactic effectiveness of maoto was 84.5%. CONCLUSION: Oral administration of maoto is suggested to be effective as PEP against nosocomial COVID-19 infection.

Development and validation of a risk assessment tool for gastric cancer in a general Japanese population.

BACKGROUND: There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese. METHODS: A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer-Lemeshow test in the validation cohort. RESULTS: During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend < 0.001). The risk assessment tool was validated internally and showed good discrimination (c-statistic = 0.76) and calibration (Hosmer-Lemeshow test P = 0.43) in the validation cohort. CONCLUSIONS: We developed a risk assessment tool for gastric cancer that provides a useful guide for stratifying an individual's risk of future gastric cancer.

A case of Turner syndrome (46XXp-/45X) complicated with Crohn's disease after hormone therapy.

A 19-year-old woman, who had been receiving hormone replacement therapy for 13 months before the diagnosis of mosaic Turner syndrome (46XXp-/45X), developed Crohn's colitis and erythema nodosum of the lower legs. Colonoscopy revealed an anal fistula and the presence of deep longitudinal ulcers with cobblestoning in the colorectum. Therapy with prednisolone and adalimumab was effective for the intestinal and skin lesions. To date, all seven case reports of Turner syndrome in Japan have also developed Crohn's disease after hormone therapy, suggesting a possible association of sex hormones in the pathogenesis.

[A case of hepatic cryptococcosis complicated by adult T-cell leukemia].

A woman in her 80s was admitted to our hospital on account of jaundice, abnormal liver function tests, and leukocytosis. She was diagnosed with adult T-cell leukemia on the basis of the presence of anti-human T-cell leukemia virus type I (HTLV-I) and the results of flow cytometric analysis of peripheral blood. She also showed lung consolidation and cavitation, and a sputum smear and culture revealed cryptococcal infection. Therefore, she was diagnosed with pulmonary cryptococcosis. However, the cause of the abnormal liver function tests and jaundice remained unclear, and the patient subsequently died. On autopsy, multiple granulomas were observed throughout the liver, consistent with cryptococcal bodies. Herein we report this rare case of hepatic cryptococcosis with predominant hepatobiliary complaints.

White blood cell count and risk of gastric cancer incidence in a general Japanese population: the Hisayama study.

The authors examined the association between white blood cell (WBC) count and the development of gastric cancer in a 19-year follow-up study of 2,558 Japanese subjects aged ≥40 years (1988-2007). The subjects were stratified into 4 groups according to baseline WBC quartile (≤4.4, 4.5-5.2, 5.3-6.3, or ≥6.4 × 10(3) cells/µL). During follow-up, 128 subjects developed gastric cancer. The age- and sex-adjusted incidence of gastric cancer increased linearly with higher WBC level: 1.7, 2.6, 3.9, and 5.4 per 1,000 person-years, respectively, for the 4 quartile groups (P for trend < 0.01). The risk of gastric cancer was 2.22-fold (95% confidence interval: 1.19, 4.14) higher in the highest WBC quartile group than in the lowest group after adjustment for confounding factors. With respect to Helicobacter pylori infection status, H. pylori-seropositive subjects in the highest WBC quartile group showed a significantly greater risk of gastric cancer than those in the lower 3 quartile groups, whereas such an association was not observed in H. pylori-seronegative subjects. There was no evidence of heterogeneity in the association (P for heterogeneity = 0.65). The study findings suggest that higher WBC levels are a risk factor for gastric cancer, especially in subjects with H. pylori infection.

Impact of anaerobic and oligotrophic conditions on survival of Alloiococcus otitidis, implicated as a cause of otitis media.

The survival of Alloiococcus otitidis (NCFB2890) with different nutritional supplements, including brain-heart infusion broth (BHI), phosphate-buffered saline (PBS), distilled water (DW), and middle ear effusion (MEE), as well as various atmospheres (aerobic, microaerobic, anaerobic), was compared using cultures, LIVE/DEAD staining, and transmission electron microscopy. The bacterial morphological traits and viability were maintained in BHI and MEE under aerobic conditions but were rapidly lost in PBS and DW. In contrast, anaerobic conditions did not support viability at all. Thus, the bacteria critically required an aerobic atmosphere for its survival as well as the appropriate nutrients, implying that culture of this pathogen from clinical specimens would become more difficult through oxygen depletion depending on a slight change in the middle ear atmosphere.

Multivariate analysis of wound complications after surgery for laryngeal and hypopharyngeal cancers.

PURPOSE: The aim of this study was to identify the factors leading to postoperative complications following surgical management of laryngeal and hypopharyngeal cancers. PROCEDURES: Between 2001 and 2008, the medical records of 107 laryngeal and hypopharyngeal cancer patients requiring laryngectomy or pharyngolaryngectomy at our hospital were reviewed. The incidence of wound complications and correlation of complications with clinicopathological factors were investigated by univariate and multivariate analysis. RESULTS: The overall incidence of wound complication was 33.6%. The complication incidence was 35.2, 21.7 and 46.2% for the primary surgery, radiation and chemoradiation groups, respectively. Diabetes mellitus and bilateral paratracheal node dissection were significantly correlated and were independent risk factors according to multivariate analysis. Bleeding from a large vessel occurred in 4 patients, and there were significant correlations with chemoradiation. CONCLUSION: Preoperative chemoradiation was not a significant risk factor for wound complication in this study. However, once postoperative wound complications occurred, they tended to produce lethal outcomes.

Jervell and Lange-Nielsen syndrome with novel KCNQ1 and additional gene mutations.

We encountered a boy with Jervell and Lange-Nielsen syndrome (JLNS) with compound heterozygous KCNQ1 mutations, maternal Trp248Phe and a novel paternal mutation, Leu347Arg. His father showed long QT (LQT) and arrhythmia. His mother was asymptomatic with no ECG abnormalities. The proband and his father had an additional mutation (SNTA1 Thr372Met), which is reportedly related to SIDS. These results suggest that multiple gene mutations influence the phenotype of KCNQ1 mutation-related arrhythmia.

Evaluation of Nasal Airflow and Resistance: Computational Modeling for Experimental Measurements.

OBJECTIVE: When evaluating nasal obstruction, conventional measurements of nasal patency do not necessarily correspond to a patient's subjective symptoms. The aim of this research is to seek an objective evaluation method by establishing computational modeling for nasal patency measurements. METHODS: We created a computer-generated geometrical model of the nasal cavity from computed-tomography scans of an adult male, presented a computational modeling method for evaluating the nasal patency in the deep-breathing state, and simulated numerically the airflow within the nasal cavity in the natural- and deep-breathing states. RESULTS: During inhalation in the natural-breathing state, the airflow was higher in the center of the nasal cavity and lower in the upper and lower portions, with the airflow characteristics being associated with the nasal functions. In the deep-breathing state, the computed nasal patency was compared with that measured experimentally by rhinomanometry. The quantitative accordance between computation and experiment was unsatisfactory, but the qualitative tendencies were similar. CONCLUSION: Through natural- and deep-breathing computations, the roles and functions of the olfactory region, nasal valve, and middle and inferior meatuses were evaluated from the flow patterns and pressure, with correlation to the nasal resistance and physiology. Above all, from the deep-breathing computation using the present computational modeling, it was deduced that the pressure difference is essential for determining the nasal sites at which the nasal resistance was produced. Thus, numerical simulation with computational modeling is potentially an objective method for evaluating nasal obstruction.

[Use of the buccal fat pad for vocal fold injection].

In recent years, autologous fat has been increasingly used for intracordal injection as a means of vocal rehabilitation in patients with deficient glottal closure, and the dipose tissue used has for the most part been harvested from the lower abdomen. However, patients differ considerably in the amount of fat available in the lower abdomen, and obtaining sufficient fat is often difficult in patents with a low body mass index (BMI). To overcome this problem we tried adopting a method that uses the buccal fat pad, as practiced in plastic surgery. The details of the method and the postoperative course are reported. The intracordal fat injection method for buccal fat pad tissue was performed in 10 cases during the 1-year from January 2005 to December 2005, and the patients' postoperative course was carefully monitored for more than 6 months after surgery. With the exception of one case, no signs of complications, such as swelling, infection, etc., were seen at the site of fat collection or in the vocal cord after the operation. Phonation was markedly improved after the injection, and the improvement was maintained throughout the observation period. Treatment of unilateral recurrent nerve paralysis by intracordal injection of autologous fat harvested from the buccal fat pad was successful.

Cetuximab with radiotherapy as an alternative treatment for advanced squamous cell carcinoma of the temporal bone.

The prognosis of advanced temporal bone cancer is poor, because complete surgical resection is difficult to achieve. Chemoradiotherapy is one of the available curative treatment options; however, its systemic effects on the patient restrict the use of this treatment. A 69-year-old female (who needed peritoneal dialysis) presented at our clinic with T4 left external auditory canal cancer and was treated with cetuximab plus radiotherapy (RT). The primary lesion showed complete response. The patient is currently alive with no evidence of disease two years after completion of the treatment and does not show any late toxicity. This is the first advanced temporal bone cancer patient treated with RT plus cetuximab. Cetuximab plus RT might be a treatment alternative for patients with advanced temporal bone cancer.

Cholesterol granuloma presenting with facial nerve paralysis following translabyrinthine surgery: A case report.

BACKGROUND: Cholesterol granuloma (CG) is a foreign body giant cell inflammatory reaction to blood degradation products, and clinically presents as a cyst with a thick fibrous lining filled with brownish-yellow fluid. We report an unusual case of CG with facial nerve paralysis 9 years after translabyrinthine (TL) surgery for vestibular schwannoma (VS) removal. CASE: A 70-year-old woman, who underwent TL surgery previously, presented with left facial palsy (FP). CT findings revealed devastated cochlea and uncovered facial nerve, and progression of FP up to House-Brackmann grade 6 was observed. Therefore, we suspected recurrence of cystic VS or facial schwannoma, although MRI was inconsistent with that of schwannoma. The cyst was completely surgically excised, and histopathology confirmed CG diagnosis. Postoperatively her facial movement improved to grade 4. Recurrence has not been encountered since 7 years. CONCLUSION: During follow-up after TL surgery for VS, care should be taken for possibility of CG occurring.

Avoidance of postoperative irradiation for cervical lymph node metastases of human papillomavirus-related tonsillar cancer.

BACKGROUND: Several reports have suggested that selected patients with human papillomavirus-related oropharyngeal cancer can be managed with surgery alone. We retrospectively reviewed tonsillar cancer cases to analyze treatment de-intensification after transoral resection. METHODS: Eighteen patients with tonsillar cancer who had undergone transoral resection were included. The patients' characteristics, p16 status, adverse features, clinical course, overall survival, and relapse-free survival according to p16 status were retrospectively examined. RESULTS: Four lesions showed positive surgical margins and one lesion showed close surgical margin; these patients were treated with postoperative irradiation. Seven p16-positive patients had multiple node metastases and two had extracapsular spread. No p16-positive patients agreed to postoperative irradiation, and recurrence within the surgical field was not observed. The five-year overall and relapse-free survival rates were 89% and 74%, respectively. The five-year relapse-free survival rates of p16-positive and p16-negative patients were 81% and 50%, respectively (p = .075). CONCLUSIONS: Postoperative irradiation for cervical lymph node metastases might be avoidable in selected patients with human papillomavirus-related tonsillar cancer. LEVEL OF EVIDENCE: 4.

Synchronous HPV-Related Cancer of Bilateral Tonsils Detected Using Transoral Endoscopic Examination with Narrow-Band Imaging.

BACKGROUND: The incidence of human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing worldwide. HPV is reported in approximately 50% cases of OPSCC in Japan. However, there are few reports of synchronous bilateral HPV-positive tonsillar carcinoma, and, in almost all those cases, carcinoma was detected using positron emission tomography/computed tomography and/or bilateral tonsillectomy. METHODS AND RESULTS: We report the case of a 63-year-old male with bilateral tonsillar carcinoma detected using transoral endoscopic examination with narrow-band imaging (NBI). A biopsy of the bilateral tonsils revealed squamous cell carcinoma, which was demonstrated to be HPV-related using in situ hybridization and p16 immunohistochemistry. The patient was diagnosed as synchronous bilateral tonsillar carcinoma: T1 (2) N2b M0. He was treated with induction chemotherapy, bilateral radical tonsillectomy with neck dissection, and radiotherapy. CONCLUSION: To our knowledge, this is the first report of a synchronous bilateral tonsillar carcinoma detected using transoral NBI in the outpatient setting. Early diagnosis without the inspection under general anesthesia is beneficial for the patients with lymph node metastasis from unknown primary lesion.

Successful detection of a minute tonsillar cancer lesion on transoral examination with narrow band imaging: A report of 2 cases.

BACKGROUND: The improvement of optical enhancement devices, such as narrow band imaging (NBI), has enabled us to visualize lesions that cannot be seen upon macroscopic examination. NBI is useful for detecting subtle lesions, including the primary sites of occult primary cancer. METHODS AND RESULTS: We describe 2 cases of tiny tonsillar cancer with positive p16 staining. Case 1 was as an occult primary cancer, and case 2 had a foreign body sensation of the pharynx. With transoral examination using a flexible video-laryngoscope with NBI, we successfully detected tonsillar cancer. These patients were treated with surgery, and the patients are currently alive with no evidence of disease more than 1 year posttreatment. CONCLUSION: We detected a small primary lesion in the palatine tonsil through transoral examination with NBI, which is a simple and noninvasive method. This approach may be useful to detect subtle lesions, especially in patients with human papillomavirus (HPV)-related tonsillar cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2421-E2424, 2016.

[Promoter hypermethylation of tumor-associated genes in head and neck cancer].

An important pathway of gene transcriptional inactivation is hypermethylation at the CpG islands of promoter regions. Some tumor suppressor genes have been reported to harbor promoter hypermethylation in head and neck cancer. We studied DNA hypermethylation of 4 genes in 42 cases of primary head and neck cancer. We applied methylation specific PCR for p16, RAR-beta, RASSF1A, and Fhit genes. Hypermethylation was detected at p16 in 43%, at RAR-beta in 40%, at RASSF1A in 12%, and at Fhit in none of the cases. Hypermethylation of at least one gene was detected in 26 (62%) of the 42 cases. No significant correlation was seen between methylation status and clinicopathological findings or prognosis. Hypermethylation of several tumor-associated genes plays an important role in tumorigenesis of head and neck cancer. We discuss clinical implications and their application.

Autologous fat augmentation of the vocal fold with basic fibroblast growth factor: Computed tomographic assessment of fat tissue survival after augmentation.

CONCLUSION: The volume of fat tissue loss after vocal fold augmentation can be decreased when augmentation is performed with addition of basic fibroblast growth factor (b-FGF). OBJECTIVES: The effectiveness of augmentation is easily decreased due to absorption. Canine experiments have confirmed that the decreased effectiveness caused by absorption after augmentation can be reduced by administering low-concentration b-FGF. Clinical application was trialed after acquiring approval from the institutional clinical review committee. METHOD: Autologous fat tissue with b-FGF was injected into the vocal folds in cases of unilateral vocal cord paralysis. This study compared fat tissue survival after injection by assessing images from computed tomography (CT). RESULTS: Assessments using CT revealed that the decrease in volume of injected fat tissue was smaller in cases treated using b-FGF than in cases using the conventional method. No severe complications were encountered using this method.

The predictive role of infiltrative growth pattern in early pharyngeal cancers.

CONCLUSION: The infiltrative growth pattern may predict tumor depth and lymph node metastasis. INF-a seems to fall into a low-risk category, and no additional treatment may be required immediately. OBJECTIVES: Tumor depth is a predictor of lymph node metastasis in early pharyngeal cancers. An infiltrative growth pattern is also a prognostic factor in other cancers. This study aimed to elucidate the predictive role of infiltrative growth pattern in early pharyngeal cancers. METHODS: Thirty-eight lesions from 37 patients who had undergone trans-oral resection of pharyngeal cancers were included. According to the Japanese Classification of Esophageal Cancer, infiltrative growth pattern was classified into three groups; INF-a, INF-b, and INF-c. The correlation between infiltrative growth pattern and tumor depth, cervical lymph node metastasis was analyzed. RESULTS: Of the 38 lesions, 25 were INF-a, nine were INF-b, and four were INF-c lesions. Lymph node metastasis was observed in three INF-b and one INF-c lesions. In contrast, no INF-a had lymph node metastasis. All INF-a lesions showed shallow invasion of the sub-epithelium; INF-b and INF-c lesions had significantly greater depth than INF-a.

Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation.

Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2-8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks.

The potential risk of vessel infiltration and cervical lymph node metastasis in hypopharyngeal superficial squamous cell carcinoma: a retrospective observational study.

CONCLUSION: The depth of hypopharyngeal superficial cancer may predict vessel infiltration and potential risk of cervical lymph node metastasis. OBJECTIVES: To elucidate the histopathological predictors of vessel infiltration and the risk of regional lymph node metastasis in hypopharyngeal superficial cancer. METHODS: This study included 31 lesions from 30 patients who had undergone transoral en bloc resection in the hospital. Patients with intraepithelial neoplasia or muscular invasion were excluded. Patient characteristics, nodal status, state of vessel infiltration, state of perineural invasion, histopathological parameters, and post-operative cervical lymph node recurrence were retrospectively examined. The histopathological parameters measured were tumor diameter and the following three parameters: tumor thickness, depth from the mucosal surface, and depth from the basement membrane. Correlations between histopathological parameters and state of vessel infiltration were statistically analyzed. RESULTS: Of the 31 lesions examined, four had vessel infiltration. Three of the four lesions with vessel infiltration had regional lymph node metastasis as well as subsequent lymph node metastasis. Lesions with vessel infiltration were significantly deeper than those without. In contrast, there was no significant difference in lesion diameters. In addition, there was no correlation between the depth and the diameter of the lesion.