Adjuvant Therapy with Immune Checkpoint Inhibitors after Carbon Ion Radiotherapy for Mucosal Melanoma of the Head and Neck: A Case-Control Study.

The development of new treatment strategies to improve the prognosis of mucosal malignant melanoma of the head and neck (MMHN) after carbon ion radiotherapy (CIRT) is essential because of the risk of distant metastases. Therefore, our objective was to evaluate the outcomes of immune checkpoint inhibitor (ICI) treatment to justify its inclusion in the regimen after CIRT. Thirty-four patients who received CIRT as an initial treatment were included in the analysis and stratified into three groups: those who did not receive ICIs (Group A), those who received ICIs after recurrence or metastasis (Group B), and those who received ICIs as adjuvant therapy after CIRT (Group C). In total, 62% of the patients (n = 21) received ICIs. The 2-year local control and overall survival (OS) rates for all patients were 90.0% and 66.8%, respectively. The 2-year OS rates for patients in Groups A, B, and C were 50.8%, 66.7%, and 100%, respectively. No significant differences were observed between Groups A and B (p = 0.192) and Groups B and C (p = 0.112). However, a significant difference was confirmed between Groups A and C (p = 0.017). Adjuvant therapy following CIRT for MMHN may be a promising treatment modality that can extend patient survival.

Point-of-care ultrasound in the head and neck region.

Point-of-care ultrasound (POCUS) in the head and neck region plays a particularly significant role in the diagnosis and treatment of upper airway stenosis, swelling, and painful diseases in the neck, and in the evaluation of swallowing function. Therefore, it should be performed in various medical settings beyond the boundaries of the clinical department such as general medicine, emergency medicine, anesthesiology, orthopedics, and pediatrics. The target diseases are salivary gland disease, lymph node disease, pharyngeal disease, laryngeal disease, esophageal disease, thyroid disease, and dysphagia and dyspnea due to various causes. Head and neck POCUS is an extremely useful diagnostic method for both patients and doctors, and its use is expected to become more widespread in the future.

Comparison of the accuracy of clinical prediction of survival and palliative prognostic index for patients with head and neck squamous cell carcinoma in the end-of-life setting.

OBJECTIVE: In the end-of-life stage of head and neck squamous cell carcinoma (HNSCC), predicting survival is essential to determine treatment procedure and place of care. Several reports have compared actual survival (AS) and clinical prediction of survival (CPS), a subjective prognostic prediction by attending physicians. However, specific studies focusing on patients with HNSCC are limited. Likewise, a comparison of the accuracy of CPS and palliative prognostic index (PPI), a prognostic tool using subjective assessment, has not been sufficiently investigated. This study aimed to clarify the correlation between AS and CPS/PPI and compare the accuracy of CPS and PPI in end-stage HNSCC. METHODS: This retrospective study included patients with HNSCC in the end-of-life setting. Patients were recruited from the National Hospital Organization Shikoku Cancer Center between April 2011 and March 2019. Data on basic demography and clinical parameters when patients decided to start end-of-life care at the head and neck oncology division were collected. We examined the correlation between AS and CPS using Spearman's correlation coefficients. The area under the receiver operating characteristic curve of CPS and PPI for 30-day survival prediction were compared for predictive accuracy. RESULTS: Among 98 eligible patients, 59 patients were enrolled in this study and analyzed. Of the 59 patients, CPS and PPI were calculated for 30 patients, whereas, only the PPI was calculated for 29 patients. The median AS and CPS were 35 (IQR: 9-73) days and 30 (IQR: 7-83) days, respectively. CPS and PPI (30 cases) were moderately correlated (r = 0.72, p<0.01). AS and CPS/PPI (30 cases) were significantly correlated (p<0.01) and showed a strong correlation (r = 0.86 and 0.80, respectively). In the 30-day survival prediction, the AUROCs of CPS and PPI (30 cases) were 0.967 (95%CI: 0.919-1) and 0.884 (95%CI: 0.767-1), respectively. Both CPS and PPI (30 cases) showed high accuracy in predicting the 30-day prognosis, with no significant difference (p = 0.077). The AUROC of PPI (59 cases) was 0.840 (95%CI: 0.711-0.969). CONCLUSIONS: AS and CPS/PPI showed significant correlations. The high accuracy of CPS may have been influenced by the fact that multiple head and neck cancer specialists at a comprehensive cancer center estimated CPS. Both CPS and PPI showed high prognostic accuracy in predicting 30-day survival. This suggests that PPI is useful in centers among physicians and healthcare workers unfamiliar with head and neck cancer.

Pulmonary Alveolar Proteinosis with Severe Respiratory Failure Improved by Segmental Lung Lavage with Fiberoptic Bronchoscopy under General Anesthesia.

Pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous materials accumulate in the alveolar compartments. A 72-year-old man was diagnosed with autoimmune PAP with severe respiratory failure. We decided to perform segmental lung lavage (SLL) with fiberoptic bronchoscopy under general anesthesia. If improvement was not significant, whole-lung lavage (WLL) would be done. SLL improved the respiratory failure and computed tomography findings. This case showed improvement in not only the area where lavage was done but also the non-lavaged area. SLL with fiberoptic bronchoscopy under general anesthesia might be an appropriate treatment option for patients with severe PAP.

Comparison of Clinical Outcomes of Definitive and Postoperative Radiotherapy for Adenoid Cystic Carcinoma of the Head and Neck: Can Definitive Radiotherapy Be a Treatment Option?

BACKGROUND: The standard treatment for adenoid cystic carcinoma of the head and neck is surgical resection followed by postoperative radiotherapy (PORT). Currently, definitive radiotherapy (defRT) is considered an inadequate treatment; however, its data are based on studies using classical radiotherapy techniques. Therefore, the therapeutic effects of current radiotherapy techniques have not been adequately evaluated, and it may have underestimated the efficacy of defRT. METHODS: We retrospectively analyzed 44 adenoid cystic carcinoma patients treated with radiotherapy based on modern treatment techniques from 1993 to 2017. RESULTS: Twenty-four patients underwent PORT and 20 patients underwent defRT. The 5-year overall survival rates for patients treated with PORT and defRT were 85.3% and 79.7%, respectively. The 5-year local control rates were 82.5% and 83.1%, respectively. There were no statistically significant differences in the overall survival and local control of patients treated with PORT and defRT (p = 0.4392 and p = 0.0904, respectively). CONCLUSION: Our results show that defRT is comparable to surgical resection followed by PORT with respect to overall survival and local control. The results suggest that defRT can be an effective treatment option for adenoid cystic carcinoma of the head and neck.

Primary advanced pulmonary synovial sarcoma treated with a multidisciplinary approach.

A 61-year-old woman was referred to our hospital due to right chest pain. A huge, 13-cm-diameter tumor was detected in the right lower lobe. For diagnostic and treatment purposes, pneumonectomy was performed, and the tumor was diagnosed as advanced pulmonary synovial sarcoma (SS) with pleural metastasis, according to immunohistochemistry analysis. Due to recurrence with brain metastases, treatment sequence composed of radiosurgery, doxorubicin, eribulin, and pazopanib was selected. The patient died after a considerably long survival of 29 months after the first visit. This case suggests that multimodal treatment may provide prolonged survival even for patients with advanced SS.

Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for blaCTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of blaCTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice.

Rosai-Dorfman disease with extranodal involvement.

Rosai-Dorfman disease is a rare condition of marrow hematopoietic stem-cell origin. Patients can show extranodal involvement as well as lymphatic involvement, but only about 5% of extranodal cases involve intracranial lesions. A 53-year-old male was admitted to our hospital with bilateral cervical lymphadenopathy. Intracranial tumors and bone lesions were also detected. Cervical lymph node biopsy and intracranial tumor resection were performed, and histopathological examination revealed Rosai-Dorfman disease. The patient showed good clinical course without significant enlargement of the tumor. This study describes the case of a patient with Rosai-Dorfman disease presenting with massive cervical lymphadenopathy mimicking malignant neoplasm.

Identification of a hepatoprotective peptide in wheat gluten hydrolysate against D-galactosamine-induced acute hepatitis in rats.

A hepatoprotective peptide, pyroglutamyl leucine (pyroGlu-Leu), was identified in wheat gluten hydrolysate through an in vivo activity-guided fractionation approach based on D-galactosamine-induced acute hepatitis in rats and fractionation of peptides with large-scale preparative ampholine-free isoelectric focusing. The active acidic fraction predominantly consisted of pyroglutamyl peptides and free pyroglutamic acid. Pyroglutamyl peptides were derivatized with phenyl isothiocyanate after removal of a pyroglutamyl residue by pyroglutamate aminopeptidase. The derivatives were purified by reversed-phase HPLC and subjected to sequence analysis. The active fraction contained pyroGlu-Ile, pyroGlu-Leu, pyroGlu-Gln, pyroGlu-Gln-Gln, and free pyroGlu. Ingestion of pyroGlu-Leu at 20 mg/kg body weight significantly decreased serum aspartate and alanine aminotransferases to approximately 30% and 20% of those values of the vehicle group, respectively, which were near the normal levels. Thirty minutes after ingestion of pyroGlu-Leu at 20 mg/kg, the concentration of pyroGlu-Leu in portal blood plasma increased to approximately 2 µM.

[Combined estrogenic activity of soybean extract used in a dietary supplement and ethinyl estradiol].

We examined the combined estrogenic activity of soybean extract used in a dietary supplement and ethinyl estradiol (EE) contained in an oral contraceptive. Olive oil (control), soybean extract (0.0036 or 0.36 g/kg corresponding to doses of total isoflavone of 0.83 or 83 mg/kg respectively), EE (1 or 10 microg/kg), and soybean extract+EE were administered to ovariectomized CD-1 mice by oral gavage for 4 consecutive days. Soybean extract (0.0036 or 0.36 g/kg) and EE (1 microg/kg) did not increase the relative uterine weight. The relative uterine weight of the soybean extract (0.0036 or 0.36 g/kg)+EE (10 microg/kg) group was significantly higher than that of the control. The relative uterine weight of the soybean extract (0.36 g/kg)+EE (10 microg/kg) group was also significantly higher than that of the EE (10 microg/kg) group. Soybean extract showed estrogenic activity for human estrogen receptor (hER)-alpha and -beta. Coadministration of EE with soybean extract increased the estrogenic activity for hER-alpha and -beta.

Identification and characterization of amidase- homologous AMI1 genes of bottom-fermenting yeast.

It has been proposed that a bottom-fermenting yeast strain of Saccharomyces pastorianus is a natural hybrid between S. cerevisiae and S. bayanus and possesses at least two types of genome. In the process of conducting expressed sequence tag (EST) analysis, we isolated bottom-fermenting yeast-specific (BFY) genes that have no significant homology with sequences in the S288C database. One of the BFY genes, AMI1, encodes a protein with homology to an amidase conserved among plants, Bacillus subtilis, Neurospora crassa, Schizosaccharomyces pombe and Saccharomyces species, with the exception of S. cerevisiae S288C. In the bottom-fermenting yeast, three alleles of AMI1 (one AMI1-A and two AMI1-B alleles) were found on different chromosomes. AMI1-A on chromosome XIII is most homologous to the S. bayanus AMI1 gene, while AMI1-B on chromosome X is most homologous to the Saccharomyces paradoxus AMI1 gene. Overproduction of AMI1 in S. cerevisiae resulted in a slow-growth phenotype. Although a hydropathy plot shows that Ami1p has a putative signal sequence, it was located in the cell, not secreted into the medium. By metabolome analysis of intracellular compounds, the amount of histidine and arginine is increased, and the amount of threonine, lysine and nicotinic acid is decreased in the Ami1p-overproducing strain as compared with the control, suggesting that Ami1p may hydrolyse some amides related to amino acid and niacin metabolism in the cell.

Identification of bottom-fermenting yeast genes expressed during lager beer fermentation.

It has been proposed that bottom-fermenting yeast strains of Saccharomyces pastorianus possess at least two types of genomes. Sequences of genes of one genome [S. cerevisiae (Sc)-type] have been found to be highly homologous (more than 90% identity) to S. cerevisiae S288C sequences, while those of the other [Lager (Lg)-type] are less so. To identify and discriminate Lg-type from Sc-type genes expressed during lager beer fermentation, normalized cDNA libraries were constructed and analysed. From approximately 22 000 ESTs, 3892 Sc-type and 2695 Lg-type ORFs were identified. Expression patterns of Sc- and Lg-type genes did not correlate with particular cell functions in KEGG classification system. Moreover, 405 independent clones were isolated that have no significant homology with sequences in the S288C database, suggesting that they include the bottom-fermenting yeast-specific (BFY) genes. Most of BFY genes have significant homology with the S. bayanus genome.

Occurrence of the free and Peptide forms of pyroglutamic acid in plasma from the portal blood of rats that had ingested a wheat gluten hydrolysate containing pyroglutamyl peptides.

In order to determine pyroglutamic acid levels in plasma, we developed a method based on precolumn derivatization of the carboxyl group of pyroglutamic acid with 2-nitrophenylhydrazine. Eight-week-old male SD strain rats were administered 200 mg of an acidic peptide fraction obtained from a commercial wheat gluten hydrolysate containing 0.63 mmol/g pyroglutamyl peptide. After administration, significant amounts of free pyroglutamic acid were observed in the ethanol-soluble fraction of the plasma from the portal vein. In addition, pyroglutamate aminopeptidase digestion of the ethanol-soluble fraction liberated significant amounts of pyroglutamic acid, which indicated the presence of the pyroglutamyl peptide. The presence of the pyroglutamyl peptide in the plasma was further confirmed by size exclusion chromatography. The levels of free and peptide forms of pyroglutamic acid increased significantly and reached a maximum (approximately 40 nmol/mL) at 15 and 30 min after administration, respectively.

Development of continuous type apparatus for ampholyte-free isoelectric focusing (autofocusing) of peptides in protein hydrolysates.

An apparatus for continuous fractionation of peptides on the basis of amphoteric nature of sample peptides was developed. A tank (66.5 cm x 8 cm x 8 cm, L x W x H) was divided into 12 compartments by a thin agarose gel layer. A drain tube (5.5 cm in length and 0.7 cm in i.d.) was fixed through the bottom of each compartment to give a height of 4 cm from the bottom. The tank with 12 compartments and electrodes was referred to as an autofocusing unit. The peptide solution or water was delivered to the sample compartments of the first unit. The solutions drained from the first unit were successively delivered to the second and third units. To the electrodes of three units, a direct electric current was applied. By using the present apparatus, peptides in casein hydrolysate can be continuously fractionated at least for 5 h. Better resolution was obtained in the second and third units.

A simple precipitation method for measuring sialic acid in apolipoprotein B-containing lipoproteins in plasma.

BACKGROUND: A convenient method for the measurement of sialic acid in plasma apoB-containing lipoproteins is described. METHODS: Dextran sulphate-Mg(2+) precipitation and enzymatic sialic acid assay were combined and applied to analysis of plasma from 96 healthy controls and 136 hyperlipidaemic subjects of types IIa (n=46), IIb (n=43), and IV (n=47). RESULTS: The sialic acid concentrations (mean+/-SD) in plasma apoB-containing lipoproteins were 19.4+/-5.9, 24.3+/-4.7 (P<0.0001 versus normal), 23.0+/-4.7 (P<0.0001), 27.9+/-5.2 (P<0.0001), and 22.3+/-3.4 mg/L (P<0.002), for normal, all types of hyperlipidaemia, types IIa, IIb, and IV, respectively. The contents of sialic acid in apoB were 2.03+/-0.41%, 2.09+/-0.35% (no significance versus normal), 1.86+/-0.27% (P<0.0001), 1.97+/-0.26% (P<0.02), and 2.28+/-0.41% (P<0.002), for normal, all types of hyperlipidaemia, types IIa, IIb, and IV, respectively. CONCLUSION: The content of sialic acid in apoB decreased significantly in type IIa but increased in type IV hyperlipidaemia, which may reflect the presence of sialic acid in very low-density lipoprotein apolipoproteins other than apoB. This simple precipitation method will be useful to evaluate the sialic acid content in low-density lipoprotein in hyperlipidaemic subjects, especially of type IIa.

Development of a large-scale (50 L) apparatus for ampholyte-free isoelectric focusing (autofocusing) of peptides in enzymatic hydrolysates of food proteins.

It has been demonstrated that peptides in enzymatic hydrolysates of proteins can be fractionated on the basis of the amphoteric nature of the sample peptides, by a laboratory-scale isoelectric focusing apparatus, without adding a chemically synthesized carrier ampholyte. This approach is referred to as autofocusing. In the present study, a large-scale (up to 50 L) autofocusing apparatus was developed and tested. A tank (125 cm x 25 cm x 20 cm) was divided into 12 compartments by 11 plates, each with a window covered in a thin agarose gel layer supported by a nylon screen (100 mesh). The compartments at both ends were filled with 0.1 N phosphoric acid (anode) and 0.1 N NaOH (cathode), respectively, functioning as electrode compartments. The remaining compartments were used for sample compartments. Autofocusing was carried out at constant voltage according to two different methods. In method 1, all sample compartments were filled with a 1% water solution of casein or milk whey protein hydrolysates. In method 2, two compartments located in the center of the tank were filled with 5% sample solution and the others were filled with deionized water. Compositional and sequence analyses of the autofocusing fractions revealed that peptides in the two hydrolysates can be fractionated within 24 h by the present apparatus. Better fractionation was obtained by method 2, whereas enrichment of some peptides occurred by using method 1.