The geriatric-8 screening tool for predicting complications in older adults after surgery for locally advanced head and neck cancer with free flap reconstruction.

PURPOSE: Radical surgery with free flap reconstruction for locally advanced head and neck cancer (HNC) is quite challenging for older adults. This retrospective study aimed to elucidate the usefulness of the geriatric-8 (G8) screening tool for predicting postoperative complications in older adults with HNC. METHODS: A retrospective review of 37 older adults with HNC who underwent radical surgery with free flap reconstruction and were assessed by the G8 screening tool was performed. Postoperative complications during hospitalization were classified according to the Clavien-Dindo classification, and possible contributing factors, including the G8 score, for major and minor complications were subjected to univariate and multivariate analyses. RESULTS: The appropriate G8 cut-off value for both major and minor complications was 12 (area under the curve 0.56 and 0.55, respectively). Multivariate logistic regression analysis showed that both smoking and lower G8 score (≤ 12) were independently associated with the severity of complications (p = 0.043, p = 0.034, respectively). CONCLUSIONS: The G8 was a possible predictor of major and minor complications in older adults with HNC who underwent radical surgery with free flap reconstruction.

A Novel SDHB IVS2-2A>C Mutation Is Responsible for Hereditary Pheochromocytoma/Paraganglioma Syndrome.

Pheochromocytomas and paragangliomas are neuroendocrine tumors which arise from adrenal medulla, and sympathetic or parasympathetic nerves, respectively. Hereditary cases afflicted by both or either pheochromocytomas and paragangliomas have been reported: these are called hereditary pheochromocytoma/paraganglioma syndromes (HPPS). Many cases of HPPS are caused by mutations of one of the succinate dehydrogenase (SDH) genes; mainly SDHB and SDHD that encode subunits for the mitochondrial respiratory chain complex II. In this study, we investigated mutations of SDH genes in six HPPS patients from four Japanese pedigrees using peripheral blood lymphocytes (from one patient with pheochromocytoma and five patients with neck paraganglioma) and tumor tissues (from two patients with paraganglioma). Results showed that all of these pedigrees harbor germline mutations in one of the SDH genes. In two pedigrees, a novel IVS2-2A>C mutation in SDHB, at the acceptor-site in intron 2, was found, and the tumor RNA of the patient clearly showed frameshift caused by exon skipping. Each of the remaining two pedigrees harbors a reported missense mutation, R242H in SDHB or G106D in SDHD. Importantly, all these mutations are heterozygous in constitutional DNAs, and two-hit mutations were evident in tumor DNAs. We thus conclude that the newly identified IVS2-2A>C mutation in SDHB is responsible for HPPS. The novel mutation revealed by our study may contribute to improvement of clinical management for patients with HPPS.

Simple laryngeal suspension procedure by suturing the digastric muscle to the periosteum of the mandible in neck dissection for tongue cancer.

PURPOSE: In this article, a simple, new laryngeal suspension procedure is described. The effect of hyoid bone suspension by suturing the digastric muscle to the periosteum of the mandible is analyzed. MATERIALS AND METHODS: To elucidate the effect of hyoid bone suspension, CT scans of 26 patients who underwent ipsilateral neck dissection with primary resection of tongue cancer were retrospectively reviewed, and the distance between the hyoid bone and the mandible was measured on the operated and unoperated sides of the neck. A total of 14 patients who underwent suturing of the digastric muscle to the mandible (digastric muscle-sutured group) and the 12 patients who did not (control group) were compared. RESULTS: In the digastric muscle-sutured group, the average distance between the hyoid bone and the mandible was significantly smaller on the operated side (17.8 ±â€¯0.57 mm) than on the unoperated side (19.8 ±â€¯0.93 mm; p < 0.05). In the control group, there was no significant difference between the operated side (21.0 ±â€¯1.42 mm) and the unoperated side (19.7 ±â€¯1.39 mm). The difference in the distance between the operated and unoperated sides was significantly larger in the digastric muscle-sutured group (1.97 ±â€¯0.79 mm) than in the control group (-1.32 ±â€¯0.61; p < 0.05). CONCLUSIONS: It was shown for the first time that suturing of the digastric muscle to the periosteum of the mandible in neck dissection with primary resection of tongue cancer resulted in hyoid bone suspension. This simple procedure can be useful for laryngeal suspension.

Central-part laryngectomy is a useful and less invasive surgical procedure for resolution of intractable aspiration.

A novel narrow-field laryngectomy procedure known as central-part laryngectomy (CPL) for less invasive laryngeal diversion in patients with intractable aspiration is introduced. We conducted retrospective case reviews of 15 patients who underwent CPL. In this procedure, an area of the glottis including the mid-part of the thyroid cartilage and cricoid cartilage is removed to separate the digestive tract from the air way. The lateral part of the thyroid cartilage, the entire hypopharyngeal mucosa and epiglottis are preserved. The superior laryngeal vessels and nerve are not invaded. All fifteen patients were relieved of aspiration without major complications. In good accordance with cutting of the cricopharyngeal muscles and removal of the cricoid cartilage, postoperative videofluoroscopy demonstrated smooth passages of barium. Ten of 12 patients who had hoped to resume oral food intake became able to do so after CPL and two others also achieved partial oral deglutition. CPL is a useful procedure for treatment of intractable aspiration and offers considerable advantages over other laryngotracheal diversion procedures from the view point of oral food intake.

Clinical characteristics and outcomes of persistent bacteremia in patients with head and neck cancer in a tertiary care hospital.

Introduction: Compared to other cancers, research on bloodstream infection in head and neck cancer is scarce, lacking comparative studies on persistent versus transient bacteremia outcomes. Methods: This retrospective survey examined patients with head and neck cancer undergoing blood culture at our center from June 2009 to May 2023. Blood culture-positive cases suspected of infection were divided into persistent bacteremia and transient bacteremia groups. We investigated their clinical, epidemiological, and microbiological features, including risk factors for persistent bacteremia and mortality. The primary outcome was 90-day mortality. Results: In this 97-patient cohort, 14 (14%) cases were assigned to the persistent bacteremia group. Catheter-related bloodstream infections were the leading cause of infection in both groups, consistently contributing to a high proportion of overall bloodstream infections. The mortality rate was generally higher in the persistent bacteremia group than in the transient bacteremia group (odds ratio [OR], 2.6; 95% confidence interval [CI], 0.6-11.1), particularly in the non-clearance subgroup (OR, 9; 95% CI, 0.5-155.2). Pyogenic spondylitis was a key risk factor for persistent bacteremia, while hypoalbuminemia increased mortality. Conclusion: In patients with bacteremia and head and neck cancer, persistent bacteremia was associated with higher mortality than was transient bacteremia. Adittionally, bacteremia clearance in persistent bacteremia is thus crucial for prognostic improvement.

Trismus after partial maxillectomy and radiotherapy: Free flap reconstruction versus prosthetic obturation.

OBJECTIVE: Partial maxillectomy and postoperative radiotherapy are both risk factors associated with trismus. This retrospective study aimed to evaluate the incidence and severity of trismus in patients following partial maxillectomy with or without postoperative radiotherapy and to compare free flap reconstruction and prosthetic obturation. METHODS: A retrospective review of 40 oral cancer patients who underwent partial maxillectomy with or without postoperative radiotherapy was performed. Maximum interincisal distance recorded at least 6 months after surgery was classified according to a revised subjective-objective management-analytical (SOMA) scale and compared between the free flap reconstruction group (n = 12) and the prosthetic obturation group (n = 28). RESULTS: Trismus was observed in 16/40 (40%) patients, and severe trismus was observed in 4/40 (10%) patients. Although no significant difference in trismus grade was observed between the free flap reconstruction and prosthetic obturation groups, both severe trismus and radiation-induced osteonecrosis were only seen in the prosthetic obturation group with postoperative radiotherapy. CONCLUSION: Free flap reconstruction was preferable to prosthetic obturation to avoid severe trismus and radiation-induced osteonecrosis in patients who underwent both partial maxillectomy and postoperative radiotherapy.

Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials.

Salivary gland cancers (SGCs) are heterogeneous tumors, and precision oncology represents a promising therapeutic approach; however, its impact on SGCs remains obscure. This study aimed to establish a translational model for testing molecular-targeted therapies by combining patient-derived organoids and genomic analyses of SGCs. We enrolled 29 patients, including 24 with SGCs and 5 with benign tumors. Resected tumors were subjected to organoid and monolayer cultures, as well as whole-exome sequencing. Organoid and monolayer cultures of SGCs were successfully established in 70.8% and 62.5% of cases, respectively. Organoids retained most histopathological and genetic profiles of their original tumors. In contrast, 40% of the monolayer-cultured cells did not harbor somatic mutations of their original tumors. The efficacy of molecular-targeted drugs tested on organoids depended on their oncogenic features. Organoids recapitulated the primary tumors and were useful for testing genotype-oriented molecular targeted therapy, which is valuable for precision medicine in patients with SGCs.

Endoscopic Resection of Nasal Mucosal Melanoma Using Temporary Transseptal Access.

Nasal mucosal melanoma (NMM) is a rare tumor with a poor prognosis. Although an endoscopic resection of malignant nasal tumor now becomes a treatment of choice when the surgical margin can be secured, it is still controversial. We report three cases of NMM that was successfully removed en bloc with clear margins by endoscopic surgery with temporal transseptal access. Cases of a 78-year-old woman, an 83-year-old man, and an 81-year-old man with NMM arising from the inferior turbinate who underwent endoscopic resection of the tumor are discussed in detail. We made temporal transseptal access using septal mucosal flaps. We moved the nasal cavity-occupying tumor to the contralateral side to create a working space to perform endoscopic en bloc resections. This technique is simple yet effective and less invasive than open craniofacial resections for removing malignancies arising from the inferior turbinate.

Investigation of the diversity of human papillomavirus 16 variants and L1 antigenic regions relevant for the prevention of human papillomavirus-related oropharyngeal cancer in Japan.

OBJECTIVE: This study aimed to investigate the distribution of human papillomavirus 16 (HPV16) variants that contribute to the development of HPV-related oropharyngeal carcinoma (HPV-OPC) in the Japanese population and to evaluate genetic variations in the sequence encoding the L1 antigen region of the viral outer shell that is targeted by existing vaccines and is relevant for designing a prevention strategy to combat the exponential increase in HPV-OPC cases in Japan. METHODS: Seventy Japanese HPV-OPC patients treated at Tohoku University Hospital were included in the study. DNA was extracted from formalin-fixed, paraffin-embedded tissue samples. Polymerase chain reaction and direct nucleotide sequencing were performed to determine the nucleotide polymorphisms necessary for the classification of HPV16 variants and to assess genetic diversity in the HPV16 L1 antigen region, including the BC, DE, EF, FG, and HI loops. RESULTS: The most common variant of HPV16 was the A4 sublineage (88.6%), conventionally called the Asian type, followed by the A1/2/3 (10.0%) sublineage, classified as the European type. The only nonsynonymous substitution detected in the L1 antigen loop region was p.N181T in the EF loop, which was found in 28/70 (40%) cases. In contrast, no nonsynonymous substitutions were observed in the DE, FG, and HI loops, which are particularly important regions in the antigen loop targeted by existing HPV vaccines. CONCLUSION: The most common HPV16 variant in Japanese HPV-OPC patients was the A4 subtype. The L1 antigen region is highly conserved, suggesting sufficient efficacy of existing HPV vaccines. These findings provide important information that will aid in the design of an HPV16 infection control strategy using existing HPV vaccines to prevent the spread of HPV-OPC in Japan.

Eustachian Tube Functions in Concurrent Chemoradiotherapy for Head and Neck Cancer Patients.

Ototoxicity is a dose-limiting adverse event for concurrent chemoradiotherapy (CCRT) with high-dose cisplatin for locally advanced head and neck squamous cell carcinoma (HNSCC). Both irradiation to the Eustachian tube (ET) and weight loss are risk factors for patulous ET. The aim of this prospective, observational study was to elucidate the incidences of patulous ET conditions before and after CCRT in HNSCC patients by means of ET function tests. This prospective, observational study was conducted in 27 HNSCC patients who received CCRT with high-dose cisplatin, and ET function tests (sonotubometry and tubo-tympano-aerodynamic graphy) were performed before and 3 months after CCRT. Factors potentially affecting the incidence of patulous ET conditions after CCRT were evaluated. Of the 54 ears from 27 patients investigated, patulous ET conditions were observed in 12 ears (22.2%) from 9 patients (33.3%) before CCRT and 15 ears (27.8%) from 11 patients (40.7%) at 3 months after CCRT. Only patulous ET conditions before CCRT in each ear were significantly associated with patulous ET conditions after CCRT (p = 0.010). This is the first report to describe the incidences of patulous ET conditions before and after CCRT in HNSCC patients. HNSCC patients are potentially at higher risk of patulous ET.

Serum selenium predicts achievement of full-dose cisplatin in concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma: A prospective, observational study.

OBJECTIVE: Concurrent chemoradiotherapy (CCRT) with three-weekly high-dose cisplatin (100 mg/m2) is a standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC), but compliance with cisplatin is often poor due to various adverse events. The aim of this prospective, observational study was to determine the predictors of achievement of full-dose cisplatin. METHODS: A prospective, observational study was conducted involving 60 patients who received CCRT with three-weekly high-dose cisplatin (100 mg/m2) for locally advanced HNSCC. Possible predictors affecting compliance with cisplatin were subjected to univariate and multivariate logistic regression analyses. Age, sex, primary site, clinical stage, treatment intent, history of hypertension, diabetes mellitus, smoking and drinking habits, body mass index, creatinine clearance, serum albumin, controlling nutrition status, trace elements (Fe, Zn, Cu, Se), acute kidney injury, white blood cell count decrease, neutrophilia, and weight loss were the variables evaluated. RESULTS: Twenty-seven patients achieved full-dose cisplatin (300 mg/m2), and the other 33 patients did not. Multivariate logistic regression analysis showed that both mild renal dysfunction and selenium deficiency before treatment independently had negative impacts on achievement of full-dose cisplatin. CONCLUSIONS: As well as renal function, selenium deficiency is a potential therapeutic target for CCRT with high-dose cisplatin in HNSCC patients.

Management of adenoid cystic carcinoma of the head and neck: a single-institute study with over 25-year follow-up.

BACKGROUND: Adenoid cystic carcinoma is a rare malignant tumor arising from exocrine glands such as the major and minor salivary glands of the paranasal sinuses or the external auditory canal. Although multiple retrospective clinical studies of ACC have been reported to date, clinical questions, such as 1) long-term prognosis beyond 20 years, 2) usefulness and suitability for treatment of therapeutic interventions, 3) therapeutic goal to aim for, and 4) prognosis by recurrence sites, are still unclear. METHODS: To improve understanding and management of adenoid cystic carcinoma of the head and neck (ACC), a retrospective study with 58 new ACC cases between 1991 and 2016 was performed. The median observation period was 66.8 months (range 3-316 months). The overall clinical stages were as follows: I, 6.9%; II, 25.9%; III, 19.0%; and IV, 48.2%. Histology was cribriform/tubular type (C-T type) in 62.0% and solid type in 27.5%. The main treatment strategy was definitive surgery, which was performed in 75.2% of cases. RESULTS: Overall 10-year, 20-year, and 25-year survivals were 63.7, 27.3, and 20.0%, respectively. Similarly, disease-specific survival (DSSs) was 65.7, 51.2, and 38.4%, respectively, and disease-free survival was 25.2, 9.4, and 9.4%, respectively. Conducting surgery (HR: 0.19, 95% CI: 0.06-0.61, p = 0.005) and C-T type (HR: 0.32, 95% CI: 0.11-0.93, p = 0.036) were independent prognostic predictors of DSS. DSS was significantly prolonged after salvage surgery for both locoregional recurrence (p = 0.004) and lung metastatic recurrence (p = 0.012, vs best supportive care). CONCLUSIONS: In ACC cases, both initial surgical treatment and repetitive surgical resection of resectable recurrent lesions, including both locoregional and lung metastases, resulted in longer survival. The major goal of treatment for ACC may be long-term survival including cancer-bearing survival, resulting in either natural death or intercurrent-disease death, since judging cure of ACC is almost impossible. TRIAL REGISTRATION: Retrospectively registered.

Long-Term Outcomes of Patients with Squamous Cell Carcinoma of the Temporal Bone after Concomitant Chemoradiotherapy.

Objectives This article aims to clarify the long-term outcomes of patients with squamous cell carcinoma of the temporal bone who underwent concomitant chemoradiotherapy (CCRT). Design and Setting The study design was a retrospective chart review. Patients and Methods From December 2001 to June 2014, 23 patients with cancer of the temporal bone who were treated by CCRT at the Tohoku University Hospital and the Iwate Medical University Hospital were enrolled in this study. For advanced cancer of the temporal bone, a modified docetaxel, cisplatin, and 5-fluorouracil (TPF) regimen was used for CCRT. The long-term outcomes, including prognoses and late complications, were analyzed after CCRT of patients with cancers of the temporal bone. Results The main long-term complications were stenosis of the external auditory canal and conductive hearing loss. No harmful late complications were observed in these patients. Disease-specific survival rates were 84.9% for all patients, 100% for patients of stage I, II, and III ( n = 10), and 75.5% for patients of stage IV ( n = 13) at 5 years. Conclusions Our study showed that CCRT is an effective treatment choice for squamous cell carcinoma of the temporal bone. Furthermore, CCRT using the TPF regimen is a safe and effective initial treatment for patients with advanced cancers of the temporal bone.

Stabilization mechanism of limaprost in solid dosage form.

The effect of polymeric pharmaceutical excipients on the degradation of limaprost by hydrolysis was assessed by near infrared (NIR) spectroscopy and spin-spin relaxation time (T(2)) measurements of proton NMR. Freeze-dried limaprost-alfadex formulated with various polymeric pharmaceutical excipients was exposed under humidified condition at 25 degrees C and 75% relative humidity. The freeze-dried limaprost-alfadex formulated with cellulose derivatives, hydroxypropylmethylcellulose (HPMC) and hydroxypropylcellulose (HPC-L), degraded easily. However, degradation was suppressed in samples formulated with polysaccharides, dextran40, dextrin, and pullulan, although the water sorption was more than 10% (w/w). A second-derivative NIR study showed the changes in the water mobility in the mixtures. The absorption peak near 1900nm, which was assigned to water with high mobility, was observed in the humidified HPMC and HPC-L. The proton NMR spin-spin relaxation time measurements indicated that the structural relaxation of a polymeric excipient changed upon humidification. The polysaccharides showed only Gaussian relaxations, but the cellulose derivatives showed Lorentzian relaxations and Gaussian relaxations. The T(2) values of the Gaussian relaxation in HPMC and HPC-L were higher than those in dextran40, dextrin, and pullulan throughout the humidifying period. The higher molecular mobility of HPMC and HPC-L is related to the mobility of water, which may accelerate limaprost degradation.

Nasal cavity epithelioid hemangioendothelioma invading the anterior skull base.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor that frequently occurs in soft tissues. Patients suffer from local recurrence and remote metastasis because of its malignant potential. Here, we present a rare case of EHE that originated from nasal cavity and invaded intracranially through the anterior skull base. CASE DESCRIPTION: This is a 27-year-old woman who presented a local physician with intermittent epistaxis and a facial pain around her nose. Preoperative studies demonstrated that the tumor invaded into anterior skull base and the dura matter. Therefore, we performed combined skull base and transnasal surgery, which achieved complete resection of the tumor. Postoperative course of the patient was uneventful. No recurrence or distant metastasis was observed in the patient for 2 years following the radical resection. CONCLUSIONS: To date, four cases of EHE in the nasal cavity were reported. This is the first case in which EHE demonstrated invasive potentials with intracranial extension. Radical surgical resection plays an important role for better management of invasive paranasal EHE.

Clinicopathological features of melanotic neuroectodermal tumor of infancy: Report of two cases.

Melanotic neuroectodermal tumor of infancy (MNTI) is an extremely rare, pigmented neoplastic entity of neural crest origin. Histological and immunohistochemical profiles indicate the presence of two components, small rounded neuroblast-like cellular areas and areas with large melanin-containing cells which consist of combination of neural, melanocytic, and epithelial cell types. Here we present two interesting cases of infants with MNTI which have different clinicopathological features. The first case is a 3-month-old female with rapidly growing MNTI involving the lacrimal sac and inferior wall of the orbital cavity, treated with total maxillectomy without orbital exenteration followed by chemotherapy. The second case is a 7-month-old male with slow-growing maxillary MNTI treated with complete surgical excision. In the female patient, histological findings revealed a predominance of neuroblast-like cellular areas and a high Ki67 index indicating rapid cellular proliferation. In the male patient however, large melanin-containing cells were dominant in this slow-growing tumor. These findings support the presence of two different types of MNTI, rapid-growing and slow-growing types, determined by the component of neuroblast-like cellular areas.

Recurrent chondro-osseous respiratory epithelial adenomatoid hamartoma of the nasal cavity in a child.

Chondro-osseous respiratory epithelial adenomatoid hamartoma (COREAH) is an extremely rare type of hamartoma. To the best of our knowledge, only 1 case has been previously reported. A 7-year-old girl presented with a case of COREAH of the bilateral nasal cavities. Polypous masses in both nasal cavities were resected endoscopically, and they were histologically diagnosed as COREAH. A large polypous mass recurred 1 year postsurgically on the right side only. A second endoscopic surgery was performed, and the lesion was confirmed to be recurrent COREAH. Hamartoma of the nasal cavity is rare and is generally considered to be self-limiting. This case suggests that nasal hamartomas may have neoplastic characteristics, and therefore require complete resection.

Assessment of reasons for referral and activities of hospital palliative care teams using a standard format: a multicenter 1000 case description.

CONTEXT: The many benefits of hospital palliative care teams (PCTs) are well known. However, their specific activities have not been fully clarified, and no standardized methods for reporting PCT activities are available. OBJECTIVES: The aim of this study was to investigate, through the use of a standard format, the activities performed by hospital PCTs in Japan. METHODS: This was a prospective observational study. A total of 21 hospital PCTs were included in this study, and each recruited approximately 50 consecutively referred patients. Participating PCTs filled in a standard form for reporting activities. RESULTS: We obtained data from 1055 patients who were referred to PCTs. Of the 1055 patients, 1005 patients (95%) had cancer. The median number of reasons for referral and problems identified by PCTs was two (0-22) and four (0-18), respectively. The two major reasons for referral were pain (63%) and anxiety/depression/grief/emotional burden (22%). The major recommendations were pharmacological treatment (74%), care for the patient's physical symptoms (49%), and support for patient's decision making (38%). The major activities performed by the PCTs were comprehensive assessment (90%), care for the patient's physical symptoms (77%), and pharmacological treatment (74%). CONCLUSION: The components of hospital PCT activities were successfully measured using the Standard Format for Reporting Hospital PCT Activity. The results of this study and the format for reporting hospital PCT activity could be effective in improving hospital PCT practice and for the education of new hospital PCT members.

Glomangiopericytoma of the nasal cavity.

Glomangiopericytoma is a rare tumor arising from the pericytes surrounding capillaries, and accounts for less than 0.5% of all sinonasal tumors. A 60-year-old male patient presented with a glomangiopericytoma of the nasal cavity manifesting as nasal obstruction and epistaxis, which was treated successfully with endoscopic excision. Histological examination showed multiplication of spindle-shaped to oval cells which reacted strongly to immunostaining for α-smooth muscle actin. Glomangiopericytoma is categorized as a borderline low malignancy tumor, which tends to recurrence. Strict follow-up is required, especially if complete resection is not achieved.

A case of myoepithelioma of the nasal cavity.

Myoepithelioma is a rare tumor, most frequently located in the salivary gland. Case reports of extra-salivary myoepithelioma are sporadic, with only one case in the nasal cavity. A 68-year-old male patient presented with a myoepithelioma of the nasal cavity manifesting as nasal obstruction and epistaxis, which was treated successfully with endoscopic excision. Histological examination revealed myoepithelial cells and myxoid stroma, which confirmed the diagnosis of myoepithelioma. The behavioral pattern is similar to if not identical with that of the mixed tumor, pleomorphic adenoma, which is benign, but the potential for recurrence is always present, especially if complete resection is not achieved.