Short-term outcomes of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) in locally advanced nasopharyngeal carcinoma.

There is an unmet need for improving survival outcomes of locally advanced nasopharyngeal carcinoma, for example, T4/ N3 stage disease. To this end, we administered induction chemotherapy (IC) with TPF (docetaxel, cisplatin, and fluorouracil) because this stage of disease is associated with a high risk of recurrence and is difficult to control with standard treatments, such as chemoradiotherapy (CRT) alone or CRT followed by adjuvant chemotherapy. The aim of this retrospective single-center study was to clarify the short-term outcomes of locally far-advanced nasopharyngeal carcinoma patients treated with IC-TPF, followed by CRT with cisplatin. Data from 11 patients were extracted from our database, indicating that the overall response rate to IC-TPF, clinical complete response rate after CRT, 1-year progression-free survival, and 1-year overall survival were 73%, 91%, 68%, and 89%, respectively. Hematological toxicity was the most common adverse event reported during IC-TPF with 64% of patients suffering grade 3 or 4 neutropenia, 55% grade 3 or 4 leucopenia and 9% febrile neutropenia. Despite the small number of patients, these data are important because there is a limited number of studies investigating IC-TPF followed by CRT in Japanese patients. This pilot study provides some indication of the short-term effectiveness and toxicity of this therapeutic approach, which may be superior to standard treatments. Long-term follow-up is warranted to assess the effectiveness of IC-TPF in terms of clinical outcome and late-phase toxicity.

Uniform infection screening allowed safe head and neck surgery during the coronavirus disease 2019 pandemic in Japan.

BACKGROUND: The purpose of this study was to determine whether a uniform infection screening protocol could be used to safely perform head and neck cancer surgery during the coronavirus disease 2019 pandemic and clarify how surgical treatment changed compared with the pre-pandemic period. MATERIALS AND METHODS: During the unprecedented coronavirus disease 2019 pandemic in Tokyo, we continued providing head and neck cancer care, guided by our own uniform screening protocol. In this study, medical records of 208 patients with head and neck malignancy, who underwent surgical treatment at our hospital during the first and second wave of pandemic for each 2-month period (first wave: 30 March 2020-30 May 2020, second wave: 14 July 2020-14 September 2020) and the 2-month pre-pandemic period (30 October 2019-30 December 2020), were analysed. RESULTS: A total of 133 patients were admitted for surgical treatment and all, except six patients with emergency tracheostomy, were screened according to the protocol. As a result, all 127 patients received surgical treatment as planned, and all 1247 medical staff members involved in the surgeries were uninfected by severe acute respiratory syndrome coronavirus 2. During the first wave of pandemic, 20% reduction of head and neck surgery was requited; however, restrictions of surgery were not necessary during the second wave. Surgical procedure, length of hospitalization, postoperative complications and number of medical staff were unchanged compared with pre-pandemic period. CONCLUSION: Our data indicate that continuation of head and neck anticancer surgical treatment in an epidemic area during the coronavirus disease 2019 pandemic were safe and feasible, if adequate and strict preventive measures are vigorously and successfully carried out.

Effect of substituting arginine and lysine with alanine on antimicrobial activity and the mechanism of action of a cationic dodecapeptide (CL(14-25)), a partial sequence of cyanate lyase from rice.

The antimicrobial activity of analogs obtained by substituting arginine and lysine in CL(14-25), a cationic α-helical dodecapeptide, with alanine against Porphyromonas gingivalis, a periodontal pathogen, varied significantly depending on the number and position of cationic amino acids. The alanine-substituted analogs had no hemolytic activity, even at a concentration of 1 mM. The antimicrobial activities of CL(K20A) and CL(K20A, K25A) were 3.8-fold and 9.1-fold higher, respectively, than that of CL(14-25). The antimicrobial activity of CL(R15A) was slightly lower than that of CL(14-25), suggesting that arginine at position 15 is not essential but is important for the antimicrobial activity. The experiments in which the alanine-substituted analogs bearing the replacement of arginine at position 24 and/or lysine at position 25 were used showed that arginine at position 24 was crucial for the antimicrobial activity whenever lysine at position 25 was substituted with alanine. Helical wheel projections of the alanine-substituted analogs indicate that the hydrophobicity in the vicinity of leucine at position 16 and alanines at positions 18 and/or 21 increased by substituting lysine at positions 20 and 25 with alanine, respectively. The degrees of diSC3 -5 release from P. gingivalis cells and disruption of GUVs induced by the alanine-substituted analogs with different positive charges were not closely related to their antimicrobial activities. The enhanced antimicrobial activities of the alanine-substituted analogs appear to be mainly attributable to the changes in properties such as hydrophobicity and amphipathic propensity due to alanine substitution and not to their extents of positive charge (cationicity).

Pharyngeal squamous cell papilloma in adult Japanese: comparison with laryngeal papilloma in clinical manifestations and HPV infection.

A number of reports have investigated the relationship between laryngeal papilloma and human papilloma virus (HPV) infection. On the other hand, it is unclear whether the HPV infection is involved in the occurrence of pharyngeal papilloma. We hypothesized that HPV infection was involved in the occurrence of pharyngeal papilloma similarly to laryngeal papilloma. To verify this hypothesis, we investigated the presence of HPV infection. Furthermore, clinical manifestations of pharyngeal papilloma, which had rarely been reported, were discussed. A male-to-female ratio, solitary or multiple occurrences, and koilocytosis were examined in cases with pharyngeal papilloma. HPV DNA was examined with unfixed surgically resected specimens of pharyngeal papilloma. A screening test by the liquid-phase hybridization method was carried out for the HPV high-risk group (16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59, and 68) and HPV low-risk group (6, 11, 42, 43, 44). As a control, 15 cases with laryngeal papilloma for which the same screening test was carried out were employed. Pharyngeal papilloma occurred as a solitary lesion more often, whereas laryngeal papilloma occurred as multiple tumors more frequently. The HPV infection rate was 0% in pharyngeal papilloma cases, which was in stark contrast with 66.7% in the HPV low-risk group in laryngeal papilloma cases. Pharyngeal papilloma occurred as a solitary lesion in females more frequently. Contrary to our hypothesis, the involvement of HPV infection was unlikely in the occurrence of pharyngeal papilloma.

Surgical technique for superselective neck dissection under local anesthesia in recurrent head and neck cancer.

The aim of this paper is to describe a safe and effective surgical technique for neck dissection under local anesthesia. An increasing number of patients cannot undergo general anesthesia due to systemic complication arising from old age. Moreover, the long-term survival of patients with recurrent or metastatic cancer due to advances in chemotherapy has increased the necessity of neck dissection under local anesthesia. Appropriate pain control and selection of medical devices are important factors for success of the surgery under local anesthesia. In addition to the usual subcutaneous infiltration anesthesia for pain control, nerve blocks for each cervical nerve encountered during surgery are extremely effective. Since muscle relaxants are not available, sharp devices such as knife or scissors, instead of electric scalpel, should be used to prevent unexpected muscle contractions caused by electric current. This video presents well-proven techniques and technical tips for superselective neck dissection under local anesthesia.

Olfactory Preservation in Craniofacial Resection of Tumor Invading Hemianterior Skull Base: Operative Video.

In traditional craniofacial resection of tumors invading the anterior skull base, the bilateral olfactory apparatus is resected. Recently, transnasal endoscopy has been used for olfactory preservation in resections of unilateral low-grade malignancies. However, for tumors that invade the orbita or for high-grade malignancies, the transnasal endoscopic skull base surgery has been controversial. This video demonstrates the surgical techniques of olfactory preservation during craniofacial resection of a high-grade malignancy invading the hemianterior skull base and orbita. We present the case of a 32-year-old woman with osteosarcoma in the right ethmoid sinus. The tumor invaded the ipsilateral cribriform plate, dura menta, and orbital periosteum; however, the nasal septum and crista galli were intact ( Fig. 1A, B ). Because the tumor was a high-grade malignancy and the orbita had been invaded, we performed craniofacial resection instead of endoscopic resection ( Fig. C2A ). We drilled into the right side of the crista galli, midline of the cribriform plate, and perpendicular plate of the ethmoid bone via craniotomy. As a result, we accessed the nasal cavity directly ( Fig. 2B ). To preserve the nasal septum, we detached the remaining right septal mucosa through the transfacial approach ( Fig. 2C ). Because of the high risk of cerebrospinal fluid leakage as a result of previous irradiation, we performed vascularized free flap reconstruction of the skull base instead of pericranial flap. Postoperative computed tomography revealed no evidence of tumor ( Fig. 1C, D ). The patient's sense of smell returned after 1 postoperative day, and she was discharged on the postoperative day 14. The link to the video can be found at: https://youtu.be/XzPABYwzkjs .

Carotid artery ligation via sternotomy as a palliative surgery: Case report of advanced intramediastinal malignant soft tissue tumor.

Under extreme conditions and in palliative settings, shared decision making with the patient is vital; narrative decisions beyond evidence could be considered. If there is a chance of symptom palliation, extended surgery should not be avoided merely because of the limited life expectancy.

Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence.

OBJECTIVES: This study aims to evaluate whether the accumulation of TP53 mutations is associated with clinical outcome by comparing full-coverage TP53 deep sequencing of the initial and recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Medical records and surgical specimens of 400 patients with HNSCC surgically treated with curative intent, of which 95 patients developed local or locoregional recurrence, were reviewed. Of these patients, 63 were eligible for genomic analysis. Full-coverage TP53 deep sequencing of 126 paired initial and recurrent tumor samples was examined using next-generation sequencing (NGS). Temporal changes in the mutation status, molecular characterization, and clinical outcome were compared. Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression models were used for statistical analysis. RESULTS: Of the recurrent tumors, 22% harbored accumulation of TP53 mutations, and 16% lost the original mutation. The accumulation of TP53 mutations was significantly more frequent in oral cancer than in pharyngeal or laryngeal cancer (33% vs. 7%, p = 0.016). Two-year post-recurrence survival (PRS) was associated with TP53 status for recurrent tumors, but not for initial tumors. The TP53 status for recurrent tumors was an independent risk factor in multivariate analysis (hazard ratio, 5.76; 95% confidence interval, 1.86-17.8; p = 0.0023). CONCLUSION: Approximately one-third of the recurrent HNSCC cases showed a different TP53 status from the initial tumor. Temporal changes in the mutation status differed by primary site. Full-coverage TP53 deep sequencing of recurrent tumors was useful in predicting post-recurrence prognosis.

Prognostic factors of recovery with medication in patients with taste disorders.

OBJECTIVES: We aimed to elucidate the prognostic factors of the patients with taste disorders who were treated with popular and common medication in Japan. MATERIALS AND METHODS: A retrospective study on the medical charts of a total of 255 patients with taste disorders who were treated primarily with oral medication including a zinc agent. RESULTS: The factors below were significantly linked with poor prognosis: 1) male gender, 2) taste disorders that began 3 months before starting treatment and 3) a severe taste disorder grade at the initial visit. CONCLUSIONS: We have concluded that the prognosis for the patients with taste disorders who were treated by popular and standard medication therapy in Japan recently was significantly linked to gender, the period of 3 months before starting the treatment and the severity of the disorder at the time of diagnosis. In addition, we recognized some limitations we should resolve in further research including a method of measuring "umami" and so on. CLINICAL RELEVANCE: Better awareness of these factors should be clinically useful when we manage patients with taste disorders. Earlier treatment should be started to cure the symptoms.

Risk Factors for Delayed Surgical Recovery and Massive Bleeding in Skull Base Surgery.

BACKGROUND: To determine factors that delay surgical recovery and increase intraoperative hemorrhage in skull base surgery. METHODS: Factors related to delayed postoperative recovery were retrospectively reviewed in 33 patients who underwent open skull base surgery. Early and late recovery phases were assessed as "days required to walk around the ward (DWW)" and "length of hospital stay (LHS)," respectively. Intraoperative blood loss was cal-culated every hour and analyzed in 4 steps, i.e., craniotomy and intracranial manipulation, cranial fossa osteotomy, extracranial osteotomy, and reconstruction. RESULTS: More than 4,000 mL of blood loss (B = 2.7392, Exp[B] = 15.4744; 95% CI 1.1828-202.4417) and comorbidi-ty (B = 2.3978, Exp[B]) = 10.9987; 95% CI 1.3534-98.3810) significantly prolonged the DWW; the occurrence of postoperative complications significantly delayed the LHS (p = 0.0316). Tumor invasion to the hard palate, the maxillary sinus, the pterygopalatine fossa, the base of the pterygoid process, the sphenoid sinus, the middle cranial fossa, and the cavernous sinus and a long operation time (>13 h) were associated with increased total hemorrhage. The optimal cut-off hemorrhage volume associated with total massive blood loss in craniotomy and intracranial manipulation (AUC = 0.8364), cranial fossa osteotomy (AUC = 0.8000), and extracranial osteotomy (AUC = 0.8545) was 1,111, 750, and 913 mL, respectively. Persistent infection (6%) and neuropsychiatric disorder (6%) are direct causes of delayed LHS. CONCLUSION: Blood loss, comorbidity, and postoperative complications were risk factors for delayed surgical recovery. Meticulous preoperative planning, intraoperative surefire hemostasis, and perioperative holistic management are prerequisites for safe skull base surgery.

Effectiveness of chemoradiotherapy for radiation-induced bilateral external auditory canal cancer: A case report and literature review.

BACKGROUND: Radiation-induced bilateral external auditory canal cancer is an extremely rare disease that has yet to be fully characterized in the clinical literature. METHODS: Herein, we present a case study of a 75-year-old man with radiation-induced bilateral external auditory canal cancer. The patient's medical history included left maxillary cancer that had been treated with chemoradiation 19 years earlier and local recurrence with total maxillectomy 10 years earlier. Intracavitary radiation was delivered to the site of postoperative recurrence 8 years before the current presentation. The patient declined radical surgery for the external auditory canal cancer at this time, and a customized combined modality regimen was thus administered. RESULTS: There was no recurrence of cancer for 22 months, to date, after completing chemoradiotherapy. CONCLUSIONS: Our finding that radiotherapy can be successfully used for radiation-induced cancer indicates that chemoradiotherapy may be a useful strategy for treating this type of malignancy.

A surgical approach to schwannomas originating from the esophageal branch of the recurrent laryngeal nerve: Pictorial essay.

BACKGROUND: Schwannoma originating from the esophageal branch of the recurrent laryngeal nerve is clinically rare event. The best approach to preoperative pathological diagnosis, surgery, and airway management for this submucosal tumor in the tracheal membranous portion remains controversial. METHODS AND RESULTS: A 69-year-old man had developed dyspnea for 6 months. Transnasal endoscopy revealed a submucosal tumor in the tracheal membranous portion, obstructing the airway. CT revealed that the tumor was located between the trachea and esophagus. Needle biopsy using ultrasonic bronchoscope diagnosed the submucosal tumor as schwannoma. Intercapsular resection was performed by a transtracheal approach under local anesthesia. The tumor was completely resected and the patient's symptoms completely improved. CONCLUSIONS: We report the treatment of a rare schwannoma originating from the esophageal branch of the recurrent laryngeal nerve. A needle biopsy using an ultrasonic bronchoscope was successfully used for diagnosis. Intercapsular resection by a transtracheal approach was effective.

OK-432 injection therapy for cystadenocarcinoma of the parotid gland: A case report.

OK-432 is an immunomodulator that has been reported to be efficacious as an injection therapy for cervical lymphomas and ranulas. We performed OK-432 injection therapy to treat a cystadenocarcinoma of the parotid gland in a 72-year-old man. The 50 × 46-mm tumor was located in the deep lobe of the gland. The tumor had compressed the glossopharyngeal, vagus, and hypoglossal nerves, causing neurally mediated syncope, hoarseness, dysphagia, and dysarthria. A concentration of 5 KE/2 ml of OK-432 was injected. Within 2 months, the cyst had disappeared; no recurrence was apparent during 59 months of follow-up. To the best of our knowledge, no previous report has described injection of OK-432 for malignant cystic disease. We describe the injection method, injection dose, and postinjection course in the hope that this information will prove useful for future applications against malignant cystic disease.

Expression and localization of taste receptor genes in the vallate papillae of rats: effect of zinc deficiency.

CONCLUSION: We found a difference in expression sites between TAS2Rs and ENaC (epithelial sodium channels). The number of TAS2R-positive cells and ENaC-positive cells were decreased in zinc-deficient diet rats. These findings suggest that decreased expression of taste receptor genes may play an important role in the onset of zinc deficiency-associated taste disorder. OBJECTIVE: The present study was aimed at histologically investigating the expression and localization of TAS2Rs and ENaC in the vallate taste buds of rats. Changes in expression of the taste receptor genes in zinc-deficient rats were also investigated. METHODS: The vallate papillae of five rats fed a normal diet and five rats fed a zinc-deficient diet were used. In situ hybridization was performed to investigate the expression and localization of TAS2Rs and ENaC. TAS2R-positive cells per taste bud were counted, and differences in number between the normal and zinc-deficient diet rats were investigated. RESULTS: In the normal rats, expression of TAS2Rs was observed specifically in the taste bud cells. In contrast, ENaC-positive cells were observed in a part of the taste bud cells and a large number of epithelial cells. Fewer cells were positive for TAS2Rs and ENaC in the zinc-deficient diet rats.

Antimicrobial activity and mechanism of action of a novel cationic α-helical dodecapeptide, a partial sequence of cyanate lyase from rice.

CL(14-25), a dodecapeptide, that is a partial region near N-terminus of cyanate lyase (CL, EC 4.3.99.1) from rice (Oryza sativa L. japonica), contains three arginine and two lysine residues. It was a novel cationic α-helical antimicrobial peptide. The antimicrobial activity of CL(14-25) against Porphyromonas gingivalis, a periodontal pathogen, was quantitatively evaluated by a chemiluminescence method that measures ATP derived from viable cells. The 50% growth-inhibitory concentration of CL(14-25) against P. gingivalis cells was 145 µM. CL(14-25), even at a concentration of 800 µM, had no hemolytic activity. When giant unilamellar vesicles (GUVs) that mimic the membrane composition of Gram-negative bacteria were used, microscopy image analysis suggested that CL(14-25) disrupted GUVs in a detergent-like manner. Therefore, CL(14-25) appears to exhibit antimicrobial activity through membrane disruption. To investigate the contribution of cationic amino acid residues in CL(14-25) to its antimicrobial activity, we synthesized four truncated CL analogs, in which one or two cationic amino acid residues were deleted from the N- and C- termini of CL(14-25). The degrees of calcein leakage from large unilamellar vesicles (LUVs) and 3,3'-dipropylthiadicarbocyanine iodide (diSC3-5) release from P. gingivalis cells induced by truncated CL analogs were closely related to their antimicrobial activities. CL analogs, which were truncated by removing an arginine residue from the N-terminus and a lysine residue from the C-terminus maintained their antimicrobial activity. However, CL analogs, which were further truncated by removing two arginine residues from the N-terminus, and an arginine and a lysine residue from the C-terminus, rarely exhibited antimicrobial activity.

Antimicrobial activity and mechanism of action of a novel cationic α-helical octadecapeptide derived from heat shock protein 70 of rice.

Hsp70(241-258), an octadecapeptide derived from the heat shock protein 70 (Hsp70) of rice (Oryza sativa L. japonica), is a novel cationic α-helical antimicrobial peptide (AMP) that contains four lysine, two arginine, and two histidine residues. The antimicrobial activity of Hsp70(241-258) against Porphyromonas gingivalis, a periodontal pathogen, and Candida albicans, an opportunistic fungal pathogen, was quantitatively evaluated using a chemiluminescence method that measures ATP derived from viable cells. The 50% growth-inhibitory concentrations of Hsp70(241-258) against P. gingivalis and C. albicans cells were 63 µM and 70 µM, respectively. Hsp70(241-258) had little or no hemolytic activity even at 1mM, and showed negligible cytotoxicity up to 300 µM. The degrees of calcein leakage from large unilamellar vesicles, which mimic the membranes of Gram-negative bacteria, and 3,3'-dipropylthiadicarbocyanine iodide release from P. gingivalis cells induced by the addition of Hsp70(241-258) increased in a concentration-dependent manner. When Hsp70(241-258) was added to calcein-acetoxymethyl ester-loaded C. albicans cells, calcein release from the cells increased in a concentration-dependent manner. Flow cytometric analysis also showed that the percentages of C. albicans cells stained with propidium iodide, a DNA-intercalating dye, increased as the concentration of Hsp70(241-258) added was increased. Therefore, Hsp70(241-258) appears to exhibit antimicrobial activity against P. gingivalis and C. albicans through membrane disruption. These results suggest that Hsp70(241-258) could be useful as a safe and potent AMP against P. gingivalis and C. albicans in many fields of health care, especially in the control of oral infections.

Development of the Casparian strip in primary roots of maize under salt stress.

The Casparian strip in the endodermis of vascular plant roots appears to play an important role in preventing the influx of salts into the stele through the apoplast under salt stress. The effects of salinity on the development and morphology of the Casparian strip in primary roots of maize ( Zea mays L.) were studied. Compared to the controls, the strip matured closer to the root tip with increase in the ambient concentration of NaCl. During growth in 200 mM NaCl, the number and the length of the endodermal cells in the region between the root tip and the lowest position of the endodermal strip decreased, as did the apparent rate of production of cells in single files of endodermal cells (the rate of cell formation being equal to the rate at which cells are lost from the meristem). The estimated time required for an individual cell to complete the formation of the strip after generation of the cell in the presence of 200 mM NaCl was not very different from that required in controls. Thus, salinity did not substantially affect the actual process of formation of the strip in individual cells. The radial width of the Casparian strip, a morphological parameter that should be related to the effectiveness of the strip as a barrier, increased in the presence of 200 mM NaCl. The mean width of the lignified region was 0.92 microm in distilled water and 1.33 microm in 200 mM NaCl at the lowest position of the strip. The mean width of the strip relative to that of the radial wall at this position was significantly greater after growth in the presence of 200 mM NaCl than in the controls, namely, 20.5% in distilled water and 33.9% in 200 mM NaCl. These observations suggest that the function of the strip is enhanced under salt stress.