Frequency of use and cost in Japan of first-line palliative chemotherapies for recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan. METHODS: From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied. RESULTS: The sample comprised 907 patients (674 were < 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens' first-month costs were 612 851-849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000-800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN. CONCLUSION: First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society.

Efficacy of Minor Salivary Glands as Indicators of Depth of Resection for Superficial Hypopharyngeal Carcinoma.

Objective: This study aimed to investigate the utility of minor salivary glands in the hypopharynx as novel indicators for safe resection of superficial hypopharyngeal carcinomas with fewer complications. Study Design: Cadaveric study. Setting: Cadavers were stored in the pathology laboratory at Kansai Medical University. Methods: Twenty-three cadaveric specimens were examined for minor salivary glands in the pyriform sinus, posterior wall, and postcricoid regions of the hypopharynx. Their count, size, and depth were assessed. Resected specimens from 5 consecutive patients with superficial hypopharyngeal carcinomas were pathologically analyzed to determine the positional relationship between cancer and minor salivary glands. Results: Minor salivary glands were present in more than 70% of patients in each region during autopsy, with the postcricoid region having a larger count and size. The glands were universally present, regardless of sex, height, or body mass index. Minor salivary glands in the pyriform sinus and postcricoid region were present at a depth of 30% from the bottom of the submucosal layer, whereas those in the posterior wall were present in the shallow muscularis. During surgery, endoscopic findings revealed minor salivary glands as small white nodules in the submucosal layer. Pathological examination of the resected specimen confirmed that the white nodule was a minor salivary gland. In addition, tumor position in relation to minor salivary glands provided an adequate margin for resection. Conclusion: Minor salivary glands may serve as reliable indicators for determining adequate deep safety margins during surgery for superficial hypopharyngeal carcinoma.

Effectiveness and outcomes of endoscopic resection for superficial pharyngeal squamous cell carcinomas.

BACKGROUND: With the development of endoscopic imaging, superficial pharyngeal squamous cell carcinoma can now be detected during routine endoscopy. Recently, the effectiveness of endoscopic resection for superficial pharyngeal squamous cell carcinoma have been reported. METHODS: This study had a retrospective single-center design that included patients with superficial pharyngeal squamous cell carcinoma who underwent endoscopic resection. A total 47 patients with 53 lesions were analyzed. RESULTS: En bloc and R0 resection rates were 83.0% and 56.6%. Local recurrence and cervical lymph node metastasis (CLNM) were detected in 1 and 3 patients during follow-up. The macroscopic type 0-I was an independent factor for CLNM. The 3-year cumulative incidence of metachronous pharyngeal squamous cell carcinoma following endoscopic resection was 33.0%, and the 5-year overall survival rate was 89.2%. CONCLUSIONS: Endoscopic resection is an effective treatment for superficial pharyngeal squamous cell carcinomas, and the macroscopic type 0-I is a useful predictor of CLNM.

Successful endoscopic resection for well-differentiated neuroendocrine tumor, Grade 1, in the hypopharynx.

Well-differentiated neuroendocrine tumor, Grade 1 (NET, G1), in the hypopharynx is extremely rare. A 62-year-old woman was referred to our clinic with a tumor in the postcricoid area. The tumor was diagnosed NET on biopsy and there were no metastatic findings on CT, therefore we performed endoscopic resection. Histologic examination revealed well-differentiated neuroendocrine tumor, Grade 1. This case was an extremely rare and valuable case in which endoscopic images can be observed in detail. Endoscopic resection was performed and successful endoscopic and histological resection was achieved.

Direct specimen collection during routine operation improves nucleic acid quality in genetic analysis samples for head and neck tumors: A retrospective study.

The nucleic acid integrity of head and neck squamous cell carcinoma (HNSCC) samples is poor, and the material available for genetic analysis is limited. Therefore, to expand the effectiveness of personalized medicine in patients with HNSCC, a new sampling method is needed. In total, 128 samples from 44 patients with HNSCC were studied: 32 genetic analysis samples (GASs) collected as 5 × 5 × 5 mm tissue fragments from resected large tumors and immediately embedded in a small formalin bottle within 10 min (i.e., the ischemic time), 43 primary tumor components (primary), 14 decalcified tumor (DC) samples, 32 metastatic tumors in lymph nodes (LNs), and 7 parakeratinized components (PKCs). The nucleic acid quality in the GAS, primary, DC, LN, and PKC groups was compared and next-generation sequencing (NGS) was performed. DNA integrity number and percentage of RNA fragments with > 200 nucleotides were significantly higher in the GAS group than those in the other groups. RNA integrity number decreased first in LN, followed by GAS, primary, and DC. No significant differences were observed in DIN, RIN and DV200 among the PKC, primary and LN. Following methyl green-pyronin staining, preserved DNA and RNA were not visualized in DC samples. Most NGS metrics did not differ significantly among primary, LN, and PKC samples. In conclusion, GASs should be collected during routine hospital activities. When the volume of viable materials is limited, PKCs should be considered for genetic analysis.

Head and Neck Solitary Fibrous Tumor Presenting as Salivary Gland Tumor: Two Case Reports and Review of the Literature.

Solitary fibrous tumors (SFTs) are soft tumors (mesenchymal origin) that most likely develop from adult mesenchymal stem cells. SFTs are not common in the head and neck region, and the characteristics of tumors in this location are unclear. The present study describes the clinicopathological findings of 2 cases of SFTs arising in the parotid gland and buccal space, presenting as salivary gland tumors. The first case is a 76-year-old man presenting with a painless tumor on the right parotid gland who subsequently underwent partial superficial parotidectomy. According to the results of histopathological analysis, the tumor consisted of stellate and spindle-shaped cells proliferating on a mucous-like substrate. Immunohistochemical staining revealed that neoplastic cells were positive for CD34, vimentin, Bcl2, and STAT6. The second case is of a 64-year-old man presenting with a painless lump on his right cheek. Based on the findings of fine needle aspiration cytology, a tumor derived from myoepithelial cells of the minor salivary gland or a nonepithelial tumor was suspected. The patient underwent surgical resection via an intraoral approach. Histopathologically, the tumor consisted of spindle-shaped cells with rod-shaped or irregular nuclei. Immunohistochemical staining revealed that the neoplastic cells were positive for CD34, CD99, Bcl2, and STAT6. Briefly, SFT should be considered in the differential diagnosis of a well-marginalized lesion in the salivary gland and oral cavity. STAT6 immunohistochemistry is the most specific and sensitive method of diagnosing SFT. A thorough understanding of the morphological changes associated with SFT and their correlation with clinical, immunohistochemical, and molecular characteristics is important to avoid misdiagnosis.

Adenoid Ameloblastoma with BRAF p.V600E Mutation Revealing Ameloblastomatous Origin: A First Case Report.

BACKGROUND: Adenoid ameloblastoma (AdAM) is a frequently recurrent tumor that shows hybrid histological features of both ameloblastoma and adenomatoid odontogenic tumor (AOT). AdAM is expected to be classified as a new subtype of ameloblastoma in the next revision of the World Health Organization (WHO) odontogenic tumor classification. However, whether AdAM is a histologic variant of ameloblastoma or AOT remains unclear. To establish a new category, genetic evidence indicating the tumor category is necessary. METHODS: We present a case of a 23-year-old Japanese woman with AdAM who underwent genetic/DNA analysis for ameloblastoma-related mutation using immunohistochemical staining, Sanger sequencing, and next-generation sequencing (NGS) analyses with reliable clinicopathological evidence. RESULTS: Immunohistochemical expression of BRAF p.V600E was diffusely positive for both ameloblastoma- and AOT-like components. Sanger sequencing and NGS analyses showed missense mutations in BRAF p.V600E (c.1799T > A), a gene that is commonly altered in ameloblastomas but not in KRAS, another gene associated with AOT. CONCLUSION: This case report is the first to provide genetic evidence on the ameloblastomatous origin of AdAM with a BRAF p.V600E mutation. A larger series of AdAM groups' molecular testing is needed to aptly classify them and prognosticate the best treatment.

Inoculation of lymphocytes from young mice prevents progression of age-related hearing loss in a senescence-associated mouse model.

Despite the increase in age-related hearing loss (ARHL) prevalence owing to increased population aging, preventive measures against ARHL have not yet been established. The immune system becomes one of the most dysfunctional systems upon aging, and immunosenescence greatly affects homeostasis and promotes systemic aging along with chronic inflammation and oxidative stress. This study aimed to determine whether immuno-rejuvenation procedures can prevent ARHL and have clinical applications as well as to analyze the communication mechanisms between the systemic immune system and the cochlea using a murine model. Lymphocytes from young mice inhibited the progression of ARHL. The method of cryopreserving these lymphocytes and inoculating them at the onset of ARHL suggests their clinical application. Mice that were administered this treatment not only maintained auditory threshold but also avoided spinal ganglion degeneration, cellular immune aging, and nitric oxide production, which causes age-related tissue damage. These findings coincide with our previous strategies against immunosenescence and neuronal aging. Therefore, the manipulation of systemic immune function may contribute not only to the prevention of ARHL but also to the development of novel anti-aging clinical measures, paving the way to healthy longevity with preserved organ function.

MMP14 expression levels accurately predict the presence of extranodal extensions in oral squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Extranodal extension (ENE) is an adverse prognostic factor for oral squamous cell carcinoma (OSCC), and patients with OSCC along with ENE require neck dissection. In this study, we developed a novel ENE histology-based pathological predictor using MMP14 expression patterns in small biopsy specimens. METHODS: A total of 71 surgically resected tissue, 64 dissected lymph node (LN), and 46 biopsy specimens were collected from 71 patients with OSCC. Immunohistochemical analyses of total MMP14 expression in the tumour nest and cancer-associated fibroblasts (CAFs) were performed using the MMP14 co-scoring system (high- or low-risk). The association analysis of MMP14 expression in metastatic LNs was performed with respect to the presence and absence of ENE. Clinicopathological analyses and multivariate examinations were performed to assess the risks of metastasis and ENE presence. The predictive value of ENE and the impact of ENE and MMP14 expression on 5-year overall survival were examined. RESULTS: High-risk MMP14 expression was detected in metastatic LN specimens with ENE. MMP14 expression in tumour nests and CAFs and its overexpression at the tumour-stromal interface significantly correlated with the presence of ENE. The MMP14 co-scoring system was an independent risk predictor for ENE, with sensitivity, specificity, and accuracy of over 80% in biopsy samples; patients with a high risk in the MMP14 co-scoring system had significantly worse prognoses in both resections and biopsies. CONCLUSION: The MMP14 co-scoring system accurately predicted ENE presence and poor prognosis via immunohistochemical evaluation of small biopsies. This system is a simple, accurate, and inexpensive immunohistochemical approach that can be used in routine pathological diagnosis for effective treatment planning.

Treg and IL-1 receptor type 2-expressing CD4+ T cell-deleted CD4+ T cell fraction prevents the progression of age-related hearing loss in a mouse model.

We investigated the association between cellular immunity and age-related hearing loss (ARHL) development using three CD4+ T cell fractions, namely, naturally occurring regulatory T cells (Treg), interleukin 1 receptor type 2-expressing T cells (I1R2), and non-Treg non-I1R2 (nTnI) cells, which comprised Treg and I1R2-deleted CD4+ T cells. Inoculation of the nTnI fraction into a ARHL murine model, not only prevented the development of ARHL and the degeneration of spiral ganglion neurons, but also suppressed serum nitric oxide, a source of oxidative stress. Further investigations on CD4+ T cell fractions could provide novel insights into the prevention of aging, including presbycusis.

Identification of risk factors for mortality and delayed oral dietary intake in patients with open drainage due to deep neck infections: Nationwide study using a Japanese inpatient database.

BACKGROUNDS: Data on risk factors for deep neck infection including descending necrotizing mediastinitis (DNM) have been limited. Using a nationwide database, the aim was identifying the factors related to patient death and delay in recovering oral intake. METHODS: Data of 4949 patients were extracted from a Japanese inpatient database between 2012 and 2017. The main outcome was survival at discharge. In a subgroup analysis of the 4949 patients with survival, the second outcome was delay in the interval between admission and full recovery of oral intake. RESULTS: Only a few factors (advanced-age, ventilation) were associated with both mortality and delayed oral dietary intake by logistic regression analyses. Conversely, several factors including DNM (adjusted-odds ratio [OR] 1.41) and repeated surgery (adjusted-OR 1.70) were significantly related only to delayed oral dietary intake. CONCLUSIONS: Although DNM was not necessarily related to mortality, patients with DNM should receive careful attention to avoid delayed oral dietary intake.

Combination of Performance Status and Lymphocyte-monocyte Ratio as a Novel Prognostic Marker for Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck.

Background/Aim: We previously presented the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This study aimed to evaluate the prognostic significance of pretreatment inflammatory biomarkers in patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy as a supplementary study of our previous retrospective cohort study. Patients and Methods: The treatment outcomes of 100 patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy were compared according to patient characteristics and pretreatment inflammatory biomarkers using a Cox proportional hazards regression model. Survival was evaluated using the Kaplan-Meier method. Results: In multivariate analysis, a lymphocyte-to-monocyte ratio (LMR) of <1.944 and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 were independent risk factors for poor overall and progression-free survival. Furthermore, we found that the PS-LMR score based on the ECOG PS and LMR could stratify patients to extract the poor prognostic characteristics of R/M-SCCHN patients treated with the EXTREME regimen as first-line therapy. Conclusion: Further evaluation is warranted to study the reliability and applicability of this novel scoring system in predicting the prognosis of R/M-SCCHN patients in the future.

Real-world Treatment Outcomes of the EXTREME Regimen as First-line Therapy for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Multi-center Retrospective Cohort Study in Japan.

BACKGROUND/AIM: This Japanese multiple-center retrospective study aimed to examine the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: A total of 100 R/M SCCHN patients treated with the EXTREME regimen as first-line therapy were analyzed. The treatment outcomes were evaluated to compare patient and treatment characteristics with overall survival. RESULTS: Patients treated with carboplatin-based EXTREME regimen showed similar overall survival with less adverse effects compared to that of patients using cisplatin. The post-progression survival was significantly longer in patients treated with second-line treatment following the EXTREME regimen than in those without second-line treatment. CONCLUSION: The carboplatin-based EXTREME regimen was more feasible with similar treatment outcomes compared to cisplatin-based EXTREME regimen. In addition, subsequent lines of therapy contributed to improvement of survival for R/M SCCHN patients.

A comparison of short-term outcomes of neck dissection for head and neck cancers using Thunderbeat™, LigaSure™ or treatment without an energy-based device: A case controlled study.

OBJECTIVE: The aim of this study was to evaluate the efficacy of the new energy-based device Thunderbeat in neck dissection (ND) for head and neck cancer. MATERIALS AND METHODS: We retrospectively examined 95 consecutive patients who underwent ND for head and neck squamous cell carcinoma between April 2013 and March 2018. The patients were divided into three groups: ND without the energy-based device (control group), ND using the LigaSure Small Jaw (LS group), and ND using the Thunderbeat Open Fine Jaw (TB group). The outcomes were compared among the three groups, as measured by the duration of ND (dissection time), blood loss during ND, and postoperative complications. We also analyzed the factors that may influence dissection time using multivariate analysis. RESULTS: Compared to the control group, dissection time was found to be significantly shorter in both energy-based device groups (LS group and TB group) (96.4, 71.1, and 66.0 min, respectively, p = 0.0015) by univariate analysis. Blood loss during ND did not differ significantly among the three groups. Multivariate analysis showed that ND using the Thunderbeat as well as elderly patients (70 years and over), less extensive surgery (3 or fewer neck levels), and absence of extracapsular invasion were independently and significantly associated with shorter dissection time (p = 0.0069, 0.0337, <0.0001, and 0.0015, respectively). The incidence of postoperative complications in the LS group (20%) tended to be higher than those in the other groups (5.6% in the control group and 3.4% in the TB group), although the differences were not significant. CONCLUSION: ND for head and neck cancers using the Thunderbeat is a safe and reliable method in terms of duration of dissection without increasing postoperative complications.

Residual Recurrent Nerve Paralysis After Esophagectomy is Associated with Preoperative Lower Serum Albumin.

Esophagectomy for esophageal cancer is invasive thoracic surgery with a high incidence rate of postoperative complications and prolongation of hospitalization, even if the standardized clinical pathway improves the outcome (mortality and morbidity). Postoperative recurrent nerve paralysis (RNP) is related to respiratory complications concomitant with prolonged hospitalization. However, it has not been elucidated which factors affect the incidence and recovery of RNP. To detect the predictive factor for postoperative RNP, we focused on preoperative serum albumin. Patients who had esophageal cancer with standard esophagectomy were evaluated. In total, 94 patients were divided into three groups depending on the presence of RNP (46 in patients without RNP, 29 in those with transient RNP who recovered within 6 months follow-up and 19 in those with residual RNP). We retrospectively investigated factors associated with residual RNP. Preoperative lower serum albumin was associated with residual RNP. In addition, days to the resumption of oral intake and duration of stay in the hospita postoperatively were delayed in the group of residual RNP. Multiple regression analysis indicated that preoperative serum albumin was a predictive factor for residual RNP. Preoperative lower serum albumin level might be linked to residual RNP which could prolong the resumption of postoperative oral intake and shorten the period of stay at the hospital after esophagectomy, leading to unfavorable outcomes for patients.

[A Clinical Study on Cervical Tuberculous Lymphadenitis].

We retrospectively examined the records of patients treated for cervical tuberculous lymphadenitis in our department and analyzed the effectiveness of the various diagnostic methods. From January 2006 to December 2013, we treated 19 cases of cervical tuberculous lymphadenitis. The ages of patients with cervical tuberculous lymphadenitis ranged from 28 to 87 years old (mean, 61.4 years), and the male-to-female ratio was 8: 11. Two of the 19 patients with cervical tuberculous lymphadenitis presented with the comorbid condition of pulmonary tuberculosis. The sensitivity of cytological examination, smears, cultures and PCR (polymerase chain reaction) technique using an aspiration procedure for cervical tuberculous lymphadenitis were 13.3%, 50%, 60% and 71.4%, respectively: Although the detection ratio of fine needle aspiration cytology alone was low, the aspiration procedure could permit a definitive diagnosis by a combination of smear, culture and PCR. The QuantiFERON test (QFT) was positive in seven of seven cases, and T-SPOT was positive in two of two cases. Thus, QFT and T-SPOT were useful as aids in the diagnosis of cervical tuberculous lymphadenitis. For early diagnosis of cervical tuberculous lymphadenitis, it is important to consider a combined multimodal approach.