Long-term outcomes of salvage transurethral high-dose-rate brachytherapy combined with external beam radiation therapy for anastomotic recurrence of prostate cancer after radical prostatectomy: A retrospective analysis.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) delivers high-dose radiation to local lesions within a short treatment period. There are no reports of salvage transurethral HDR-BT for biochemical recurrence (BCR) after radical prostatectomy. Thus, we aimed to evaluate the usefulness of salvage transurethral HDR-BT with external beam radiation therapy (EBRT) for anastomotic prostate cancer recurrence. METHODS AND MATERIALS: Patients with postoperative prostate cancer who underwent salvage transurethral HDR-BT with EBRT for anastomotic recurrence at our hospital between January 2002 and July 2009 were retrospectively evaluated. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. RESULTS: Nine patients were included in this study. The median follow-up period and age were 13.1 (range 4.3-18.4) years and 67 (range 63-78) years, respectively. The dose of HDR-BT ranged from 13 to 24 Gy per 2 to 5 fractions, while that of EBRT ranged from 30 to 44 Gy per 15 to 22 fractions. The 1-year, 5-year, and 10-year bFFF rates were 77.8%, 41.7%, and 13.9%, respectively. The 10-year and 15-year CSS rates were 100% each. The 10-year and 15-year OS rates were 100% and 64.3%, respectively. Six patients were diagnosed with BCR. Two patients experienced Grade 3 hematuria as a late adverse event. There was no exacerbation of urinary incontinence. CONCLUSIONS: No prostate cancer-related deaths were observed, even after a long-term follow-up. Salvage transurethral HDR-BT after radical prostatectomy is safe and feasible and may be a useful treatment option.

Comparing the Diagnostic Accuracy of Ultrasonography, CT, MRI, and PET/CT in Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma.

(1) Background: In oral cancer staging, ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) with positron emission tomography/computed tomography (PET/CT) are routinely used in clinical practice. The present study is a retrospective examination of the diagnostic accuracy of cervical lymph node metastasis using US, CT, MRI, and PET/CT, with histopathological diagnosis as a reference, to compare the different diagnostic imaging modalities. (2) Methods: The participants included 16 patients with oral squamous cell carcinoma who underwent US-, CT-, MRI-, and PET/CT-based preoperative diagnostic imaging and simultaneous primary lesion resection and neck dissection, including 82 level regions and 424 lymph nodes. We compared the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of each imaging modality based on the imaging results and the pathology results of metastasis. (3) Results: Of the four diagnostic imaging modalities, PET/CT exhibited the highest sensitivity but the lowest specificity and accuracy. US, CT, and MRI had high specificities. Comparing each level region and lymph node showed that differences were observed in PET/CT. (4) Conclusions: PET/CT to diagnose lymph node metastasis requires a comprehensive evaluation because it produces more false positives than other diagnostic imaging modalities. Using US, CT, and MRI, which have excellent spatial resolution, improves diagnostic accuracy at the lymph node level.

Diagnostic application of intraoral ultrasonography to assess furcation involvement in mandibular first molars.

OBJECTIVES: The objectives were to clarify if intraoral ultrasonography (USG) is: (1) more accurate than conventional periodontal examinations in detection of furcation involvement, and (2) comparable to conventional periodontal examinations in accurate horizontal classification of furcation involvement in comparison to cone beam computed tomography (CBCT). METHODS: The buccal furcation in 61 lower first molars were evaluated with conventional periodontal examinations, intraoral USG and CBCT. The presence and classification of the horizontal depth of furcation involvement were defined clinically by assessment with a Nabers periodontal probe and a periapical radiograph with reference to the bone loss under the fornix. The horizontal depth of furcation involvement was measured in intraoral USG and CBCT images. Based on the measurements, presence diagnosis and horizontal classification were performed. Results from conventional periodontal examinationsand intraoral USG were compared with those from CBCT. RESULTS: κ value (κ) for agreement of presence diagnosis of furcation involvement between intraoral USG and CBCT was 0.792, while agreement with conventional periodontal examinations was 0.225. Diagnostic accuracy of intraoral USG exhibited higher values (sensitivity: 98.3%, accuracy: 98.4 %) than conventional periodontal examinations (81.4% and 81.9 %). Weighted κ statistics showed substantial agreement in the classification between intraoral USG and CBCT (κ = 0.674). High agreement (ICC: 0.914) for the measurement of horizontal depth of furcation involvement was found between intraoral USG and CBCT. CONCLUSIONS: Intraoral USG may be a reliable diagnostic tool for assessment of furcation involvement of mandibular molars with a similar performance to CBCT, but without ionizing radiation.

Masticatory muscle tendon-aponeurosis hyperplasia that was initially misdiagnosed for polymyositis: a case report and review of the literature.

BACKGROUND: Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a relatively newly identified clinical condition that manifests as trismus with a square-shaped mandible. Herein, we report a case of MMATH that was initially misdiagnosed for polymyositis due to trismus and simultaneous lower limb pain, with literature review. CASE PRESENTATION: A 30-year-old woman had a history of lower limb pain after exertion for 2 years. Initial physical examination had been performed at the Department of General Medicine in our hospital. There was also redness in the hands and fingers. Although polymyositis was suspected, it was denied. The patient visited our department for right maxillary wisdom tooth extraction. Clinical examination revealed that the patient had a square-shaped mandible. The maximal mouth opening was 22 mm. There was no temporomandibular joint pain at the time of opening. Furthermore, there was awareness of clenching while working. Panoramic radiography revealed developed square mandibular angles with flattened condyles. Computed tomography showed enlarged masseter muscles with high-density areas around the anterior and lateral fascia. Magnetic resonance imaging also showed thickened tendons and aponeuroses on the anterior surface and inside bilateral masseter muscles. Finally, the patient was diagnosed with MMTAH. Bilateral aponeurectomy of the masseter muscles with coronoidectomy and masseter muscle myotomy was performed under general anesthesia. The maximum opening during surgery was 48 mm. Mouth opening training was started on day 3 after surgery. Histopathological examination of the surgical specimen showed that the muscle fibers were enlarged to 60 µm. Immunohistochemistry testing for calcineurin, which was associated with muscle hypertrophy due to overload in some case reports, showed positive results. Twelve months after surgery, the mouth self-opening and forced opening were over 35 mm and 44 mm, respectively. CONCLUSIONS: Herein, we report a case of MMATH. Lower limb pain due to prolonged standing at work and overload due to clenching were considered risk factors for symptoms onset of MMATH.

Efficacy of Essential Oils in Relieving Cancer Pain: A Systematic Review and Meta-Analysis.

Over 80% of patients affected by cancer develops cancer-related pain, one of the most feared consequences because of its intractable nature, particularly in the terminal stage of the disease. Recent evidence-based recommendations on integrative medicine for the management of cancer pain underline the role of natural products. The present systematic review and meta-analysis aims at appraising for the first time the efficacy of aromatherapy in cancer pain in clinical studies with different design according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieves 1002 total records. Twelve studies are included and six are eligible for meta-analysis. The present study demonstrates significant efficacy of the use of essential oils in the reduction of the intensity of pain associated with cancer (p < 0.00001), highlighting the need for earlier, more homogeneous, and appropriately designed clinical trials. Good certainty body of evidence is needed for effective and safe management of cancer-related pain using essential oils by establishment of a step-by-step preclinical-to-clinical pathway to provide a rational basis for clinical use in integrative oncology. PROSPERO registration: CRD42023393182.

The Relationship between the Contouring Time of the Metal Artifacts Area and Metal Artifacts in Head and Neck Radiotherapy.

(1) Background: The impacts of metal artifacts (MAs) on the contouring workload for head and neck radiotherapy have not yet been clarified. Therefore, this study evaluated the relationship between the contouring time of the MAs area and MAs on head and neck radiotherapy treatment planning. (2) Methods: We used treatment planning computed tomography (CT) images for head and neck radiotherapy. MAs were classified into three severities by the percentage of CT images containing MAs: mild (<25%), moderate (25−75%), and severe (>75%). We randomly selected nine patients to evaluate the relationship between MAs and the contouring time of the MAs area. (3) Results: The contouring time of MAs showed moderate positive correlations with the MAs volume and the number of CT images containing MAs. Interobserver reliability of the extracted MAs volume and contouring time were excellent and poor, respectively. (4) Conclusions: Our study suggests that the contouring time of MAs areas is related to individual commitment rather than clinical experience. Therefore, the development of software combining metal artifact reduction methods with automatic contouring methods is necessary to reducing interobserver variability and contouring workload.

Visual evaluation for the elasticity of suprahyoid muscles using sonographic elastography during tongue pressure measurement: A pilot study.

BACKGROUND: Suprahyoid muscles behavior during the tongue lifting movement has not yet been elucidated. OBJECTIVE: The purpose of this study was to investigate the potential of elastography imaging to examine developmental oral dysfunction in children and oral hypofunction in older adults using sonography. METHODS: Tongue pressure was measured using a manometer with a probe. The tongue pressure was measured with simultaneously scanning the geniohyoid muscle (GHM) and the anterior belly of the digastric muscle (DGM) using sonographic elastography. Sagittal images of the GHM and coronal images of the DGM were used for the strain ratio measurement. The strain ratio of the muscles was measured three times for each subject with the tongue pressure values of 0-30 kPa. RESULTS: The strain ratio of the GHM were higher than those of the DGM at tongue pressure of 10, 20 and 30 kPa. The strain ratio of the GHM increased as the tongue pressure increased in all participants. In contrast, the strain ratio of the DGM tended to slowly decrease as tongue pressure increased in female participants. CONCLUSION: Sonographic elastography is useful for visual and quantitative evaluation of elastic properties in suprahyoid muscles during tongue lifting movements.

Macroscopic Anatomy of the Layered Structures of Facial Muscles and Fasciae in the Temporal-Malar-Mandible-Neck Region.

The layered structures of facial muscles and their topographical relationship with facial fasciae are still not fully understood. This study aimed to clarify the layered structures of facial muscles and fasciae in the temporal-malar-mandible-neck region. Thirty-four human cadavers were examined during gross anatomy courses at Niigata University (2017-2020). The face was composed of 3-layered (deep, middle, and superficial) fasciae and 4-layered facial muscles (first superficial, second superficial, third, and fourth muscle layers) according to the attachment of muscles and their topographical relationship with the fasciae. The deep fascia covered the temporal and masseter muscles. The parotid gland and facial nerves were enveloped in the middle fascia. The superficial fascia was continuous with the second superficial muscle layer. The connection between fourth and superficial muscles was at the malar and buccal areas, where the platysma blended with the masseter and the plural muscles blended with the buccinator. Our findings suggest that cooperation between the 4-layered structure of the facial muscles surrounding the apertures of the eyes and mouth and the superficial fascia enables humans to produce complex facial expressions. Furthermore, the spread of inflammation in the face may be owing to the layered facial muscles and fasciae, as these layered structures separate tissues into multiple compartments.

Examination of factors affecting condylar bone changes following surgical-orthodontic treatment.

OBJECTIVE: To identify factors affecting condylar bone changes following surgical-orthodontic treatment. METHODS: A total of 200 patients with dentofacial deformities were classified into skeletal Classes I, II, and skeletal Class III groups consisting of 61 and 139 subjects, respectively. Temporomandibular joints (TMJs) were evaluated using clinical findings and computed tomography images before treatment, immediately before surgery, and 6 months after surgery. RESULTS: Condylar bone changes occurred at a significantly higher rate after surgery in both groups. Factors related to condylar bone changes following surgical-orthodontic treatment included skeletal Class I or II, disc displacement, and condylar bone changes before treatment. There were three cases with condylar bone changes after surgery that were diagnosed with condylar resorption and skeletal Class II and anterior disc displacement before surgery. CONCLUSION: Condylar resorption could occur when the load on the condyle increases after orthognathic surgery and exceeds the permissible limit.

Analgesic Characteristics of NanoBEO Released by an Airless Dispenser for the Control of Agitation in Severe Dementia.

Chronic pain is one of the most common causes of the need for clinical evaluation, acquiring more importance in the elderly with cognitive impairment. Reduced self-reporting capabilities cause unrelieved pain contributing to the development of agitation. Safe and effective pain treatment can afford the management of agitation without the serious increase in death risk associated with neuroleptics. To this aim, the essential oil of bergamot (BEO), proven by rigorous evidence to have strong preclinical anti-nociceptive and anti-allodynic properties, has been engineered (NanoBEO, patent EP 4003294) to allow randomized, double-blind, placebo-controlled trials (BRAINAID, NCT04321889). The present study: (1) assesses the analgesic effects of a single therapeutic dose of NanoBEO, as supplied by an airless dispenser for clinical translation, in models of inflammatory, neuropathic, and sensitization types of pain relevant to clinic; (2) provides a dose-response analysis of the efficacy of NanoBEO on scratching behavior, a typical behavioral disturbance occurring in dementia. A single therapeutic dose of NanoBEO confirms efficacy following thirty minutes pre-treatment with capsaicin and on the central sensitization phase induced by formalin. Moreover, it has an ID50 of 0.6312 mg and it is efficacious on static and dynamic mechanical allodynia. Altogether, the gathered results strengthen the potential of NanoBEO for clinical management of pain and agitation.

A comparative study between CT, MRI, and intraoral US for the evaluation of the depth of invasion in early stage (T1/T2) tongue squamous cell carcinoma.

OBJECTIVES: This study aimed to clarify the accuracy of intraoral ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) in preoperative image depth of invasion (DOI) measurement of T1/T2 tongue cancer through comparison with histopathological measurements. METHODS: Imaging of the primary lesions was performed at our hospital; the lesions were classified into T1 and T2 based on the 8th edition of the AJCC/UICC, and surgery performed. There was histopathological confirmation of lesions as squamous cell carcinoma in 48 patients with tongue cancer. T3 and T4 cases, cases in which preoperative chemotherapy and radiation therapy were performed, and cases where biopsy was performed before imaging were excluded. The radiological DOI in US, CT, and MRI and the histopathological DOI as base were comparatively investigated and statistical analyses were performed by Bland-Altman analysis and Spearman's rank correlation coefficient. RESULTS: Bland-Altman analysis showed that the US radiological DOI was overestimated by an average of 0.2 mm compared to the histopathological DOI, while CT and MRI radiological DOI were overestimated by an average of 2-3 mm. The comparison of CT and MRI revealed that the difference between the MRI and histopathological DOI, as well as the 95% limit of agreement, were smaller than those of the CT radiological DOI. CONCLUSIONS: US is the most accurate preoperative diagnostic tool for T1 and T2 squamous cell carcinoma; CT and MRI tend to have an overestimation of about 2-3 mm and so caution is required.

Melanotic neuroectodermal tumor of infancy in the mandible: A case report.

RATIONALE: Melanocytic neuroectodermal tumor of infancy (MNTI) is a rare benign pigmented neoplasm that arises from the neural crest and has an aggressive growth pattern. It is predominantly seen in infants under 1 year of age, and the most common site of involvement is the maxilla. The currently accepted treatment is removal by surgical resection. Herein, we report a case of MNTI that involved the anterior alveolar ridge of the mandible in a 6-month-old infant. PATIENT CONCERNS: A case of a 6-month-old male child with a huge mass in the anterior alveolar ridge of the mandible. DIAGNOSIS: The tumor was diagnosed using histopathological and immunohistochemical techniques on the biopsy specimen obtained following incisional biopsy. Based on the findings, a final diagnosis of MNTI was established. INTERVENTIONS: Radical resection of the tumor was performed, after determining the extent of resection by referring to the mandibular 3D model created using the pre-operative CT data. OUTCOMES: The postoperative course was uneventful, and no recurrence has been observed to date for more than 4 years after surgery. LESSONS: This case emphasizes that early diagnosis and radical surgery are critical to the effective treatment, as MNTI exhibits rapid and destructive growth. It also requires careful and close follow-up because of high recurrence rates.

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders in the oral cavity: a clinicopathologic study of 4 cases and literature review.

OBJECTIVES: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OI-LPD) have been reported as one of the adverse effects of immunosuppressive therapy. The aim of this study was to describe the clinicopathologic and immunohistochemical features of OI-LPD in the oral cavity. STUDY DESIGN: Immunohistochemistry was performed to describe the immunohistochemical features in our 4 cases. The results were analyzed along with 62 cases of oral OI-LPD in the English and Japanese literature to define clinical and pathologic characteristic features. RESULTS: In our immunohistochemical analysis, Epstein-Barr virus (EBV)-positive OI-LPD showed a higher percentage of mouse double minute 2-positive cells than EBV-negative samples. A literature survey revealed that OI-LPD (including the present cases) arises primarily in the gingiva, followed by the tongue, and usually occurs with a male-to-female ratio of 1:1.9. The rate of EBV positivity was 93.8%. Further, 31 of 66 patients had osteonecrosis of the jaw and 24 of 31 patients had taken multiple immunosuppressive drugs in combination. CONCLUSIONS: We can therefore conclude that the overexpression of mouse double minute 2 in OI-LPD is associated with EBV infection, and the combination of multiple immunosuppressive drugs may be a risk factor for osteonecrosis of the jaw.

Spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis: a case report.

BACKGROUND: Spindle cell squamous cell carcinoma is an uncommon variant of squamous cell carcinoma; its diagnosis is sometimes challenging because it histopathologically resembles neoplastic or reactive spindle cell lesions of mesenchymal origins. Here, we report a rare case of spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis. CASE PRESENTATION: A 69-year-old Japanese man presented with pain and a polypoid mass on the lower left gingiva. He had received chemoradiotherapy for squamous cell carcinoma of the buccal mucosa 15 years prior to this consultation. In addition, he was treated for mandibular osteonecrosis 6 years after chemoradiotherapy without evidence of cancer recurrence. A biopsy revealed atypical spindle or pleomorphic cells scattered in the edematous and fibrin-rich stroma; however, no malignant squamous components were apparent. These atypical cells frequently contained neutrophils within their cytoplasm that formed cell-in-cell figures. Immunohistochemically, the atypical cells were negative for cytokeratins, epithelial membrane antigen, and E-cadherin, but positive for p63, vimentin, and p53. Although these findings suggested spindle cell squamous cell carcinoma, it was difficult to reach a definitive diagnosis. Based on a clinical diagnosis of a malignant tumor, the patient underwent a hemimandibulectomy. The surgically resected specimen had a typical spindle cell squamous cell carcinoma histology consisting of biphasic spindle cells and conventional squamous cell carcinoma components. Moreover, the surgical specimen also exhibited spindle tumor cells that frequently included neutrophils, around which intense staining for lysosomal-associated membrane protein 1 and cathepsin B was observed. This suggested that the cell-in-cell figures represent active neutrophil phagocytosis by tumor cells, and not emperipolesis. CONCLUSION: The presence of neutrophil phagocytosis may be a potent indicator of malignancy.

Posterior superior alveolar nerves contribute to sensation in the anterior teeth.

BACKGROUND: There is no available data on the occurrence rate of a converged alveolar canal, the detailed three-dimensional (3D) courses of alveolar canals/grooves (ACGs), or the contribution of each superior alveolar nerve to each area in the maxilla. This study aimed to clarify the 3D courses of ACGs, the relationship between ACGs and superior alveolar nerves, and the contribution of posterior superior alveolar nerves (PSANs) using computed tomography (CT) with histological analysis. METHODS: During the gross anatomy course at Niigata University, we investigated nine human cadavers. RESULTS: All anterior and posterior ACGs converged into the common alveolar canal, which contained blood vessels and several nerve bundles surrounded by perineurium, located at the nasal floor near the pyriform aperture. Histometrical analysis clarified that 16.3% of the nerve bundles in this canal were derived from PSANs, and 67% of the bundles were dispersed while they coursed down to the nasal floor. There seems to be no relationship between the density of nerve bundles in the canal and the number of remaining anterior teeth. CONCLUSIONS: Data obtained from observing the detailed 3D courses of anterior and posterior ACGs, and their relationship with superior alveolar nerves, suggest that PSANs partially contribute to the nociception of the anterior teeth.

General rules for clinical and pathological studies on oral cancer (2nd edition): a synopsis.

For doctors and other medical staff treating oral cancer, it is necessary to standardize the basic concepts and rules for oral cancer to achieve progress in its treatment, research, and diagnosis. Oral cancer is an integral part of head and neck cancer and is treated in accordance with the general rules for head and neck cancer. However, detailed rules based on the specific characteristics of oral cancer are essential. The objective of this article was to contribute to the development of the diagnosis, treatment, and research of oral cancer, based on the correct and useful medical information of clinical, surgical, pathological, and imaging findings accumulated from individual patients at various institutions. Our general rules were revised as the UICC was revised for the 8th edition and were published as the Japanese second edition in 2019. In this paper, the English edition of the "Rules" section is primarily presented.

Clinical guidelines for the application of panoramic radiographs in screening for osteoporosis.

Osteoporotic fractures are associated with an increased risk of subsequent fractures, a higher rate of mortality, and incremental medical costs. Incidental findings, which include some measurements related to the mandibular inferior cortex and the alveolar trabecular bone pattern of the mandible determined on panoramic radiographs, are considered to be a useful tool for identifying asymptomatic individuals at risk of having osteoporosis and/or fragility fractures. We undertook a worldwide literature survey and present the following clinical recommendations. Postmenopausal female dental patients with a mandibular inferior cortical width of less than 3 mm on panoramic radiographs may be at risk of having low skeletal bone mineral density (BMD) or osteoporosis, but not fragility fractures. In addition, those with a severely eroded mandibular inferior cortex may have an increased risk of having low skeletal BMD, osteoporosis, and fragility fractures. The alveolar trabecular bone pattern of the mandible might be useful for identifying female dental patients at risk of having fragility fractures, although further investigation is necessary to confirm this possibility. These incidental findings on panoramic radiographs, when used for identifying asymptomatic postmenopausal female patients at risk of having osteoporosis in general dental practice, may be helpful in reducing the incidence of first fractures, with a consequent reduction in the secondary fractures, medical costs, and mortality associated with osteoporotic fragility fractures, without incurring any additional cost.

A cost-minimization analysis of measures against metallic dental restorations for head and neck radiotherapy.

The aim of this study was to compare the estimated public medical care cost of measures to address metallic dental restorations (MDRs) for head and neck radiotherapy using high-energy mega-voltage X-rays. This was considered a first step to clarify which MDR measure was more cost-effective. We estimated the medical care cost of radiotherapy for two representative MDR measures: (i) with MDR removal or (ii) without MDR removal (non-MDR removal) using magnetic resonance imaging and a spacer. A total of 5520 patients received head and neck radiation therapy in 2018. The mean number of MDRs per person was 4.1 dental crowns and 1.3 dental bridges. The mean cost per person was estimated to be 121 720 yen for MDR removal and 54 940 yen for non-MDR removal. Therefore, the difference in total public medical care cost between MDR removal and non-MDR removal was estimated to be 303 268 800 yen. Our results suggested that non-MDR removal would be more cost-effective than MDR removal for head and neck radiotherapy. In the future, a national survey and cost-effectiveness analysis via a multicenter study are necessary; these investigations should include various outcomes such as the rate of local control, status of oral mucositis, frequency of hospital visits and efforts of the medical professionals.

Radiological imaging features of the salivary glands in xerostomia induced by an immune checkpoint inhibitor.

The clinical features of xerostomia induced by immune checkpoint inhibitors (ICI) are similar to those of Sjögren's syndrome (SS), whereas the immunohistological and serological features are known to differ from those of SS. However, the radiologic imaging features of salivary glands are not yet well known. We report a case of a 56-year-old male patient diagnosed with ICI-induced xerostomia. The patient underwent various imaging examinations to investigate the condition of the salivary glands, which indicated the following: (1) less specific findings on contrast-enhanced computed tomography, (2) mixed with intermediate and low signal intensity on both T1-weighted and fat-suppressed T2-weighted magnetic resonance imaging and poor "salt and pepper" appearance on magnetic resonance sialography, and (3) multiple ovoid hypoechoic areas with hyperechoic bands without acute sialadenitis on ultrasound. These radiologic imaging findings suggested remarkable lymphocyte infiltration, which could be a characteristic of ICI-induced xerostomia.

Contribution of Histamine to Nociceptive Behaviors Induced by Intrathecally Administered Cholecystokinin-8.

The involvement of spinal release of histamine in the nociceptive behaviors induced by cholecystokinin-8 (CCK-8) was investigated in mice. Intrathecal (i.t.) injection of CCK-8 elicited the nociceptive behaviors consisting of biting and licking. The nociceptive behaviors induced by i.t. treatment with CCK-8 showed two bell-shaped patterns. The histamine H3 receptor antagonist significantly promoted the nociceptive behaviors induced by CCK-8 at doses of 1-100 fmol and 100 pmol. The nociceptive behaviors elicited by CCK-8 was inhibited by i.t. administration of the CCK-B receptor antagonist in a dose-dependent manner, but not by the CCK-A receptor antagonist. The nociceptive behaviors induced by CCK-8 were markedly suppressed by i.t. pretreatment with antiserum against histamine and were abolished in histidine decarboxylase-deleted gene mice. In histamine H1 receptor-deleted gene mice, the nociceptive behaviors induced at both 10 amol and 10 pmol of CCK-8 were not affected. The tachykinin neurokinin-1 (NK1) receptor antagonists inhibited CCK-8 (10 pmol)-induced nociceptive behaviors in a dose-dependent manner. CCK-8 (10 amol)-induced nociceptive behaviors was not antagonized by co-administration with the tachykinin NK1 receptor antagonists. The nociceptive behaviors elicited by CCK-8 were inhibited by i.t. administration of the antagonist for the N-methyl-D-aspartate (NMDA) receptor in a dose-dependent manner. Our results suggest that the nociceptive behaviors induced by i.t. administration of CCK-8 (10 pmol) are mediated through the spinal release of histamine and are elicited via activation of the tachykinin NK1 and NMDA receptors, whereas the nociceptive behaviors induced by i.t. administration of CCK-8 (10 amol) are mediated through the spinal release of histamine and elicited via NMDA receptor activation.