Anti-centromere antibody positivity is an independent variable associated with salivary gland ultrasonography score in Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands. SS also exhibits extra-glandular manifestations and specific autoantibodies. Salivary gland ultrasonography (SGUS) is a common procedure used to assess the severity of glandular involvement. However, the association between SGUS and extra-glandular lesions remains poorly understood. This study aimed to identify clinical indices, including disease activity, associated with glandular involvement using SGUS in patients with SS. We included 115 patients with SS and 90 without SS. Patients with SS had significantly higher ultrasonography (US) score than patients without SS. Multivariate analysis revealed focus score, Saxon test positivity, and anti-centromere antibody (ACA) positivity as independent variables associated with the US score in patients with SS. In addition, these results were similar to those obtained in patients with primary SS. Patients with SS and ACA positivity had higher US score and an increased prevalence of hyperechoic bands in the parotid glands and submandibular glands. In conclusion, this study indicated that ACA positivity is associated with the US score in patients with SS. These results suggest that US findings in patients with ACA positivity might show specific changes in the salivary glands, especially fibrosis.

Metastatic Lymph Node Detection on Ultrasound Images Using YOLOv7 in Patients with Head and Neck Squamous Cell Carcinoma.

Ultrasonography is the preferred modality for detailed evaluation of enlarged lymph nodes (LNs) identified on computed tomography and/or magnetic resonance imaging, owing to its high spatial resolution. However, the diagnostic performance of ultrasonography depends on the examiner's expertise. To support the ultrasonographic diagnosis, we developed YOLOv7-based deep learning models for metastatic LN detection on ultrasonography and compared their detection performance with that of highly experienced radiologists and less experienced residents. We enrolled 462 B- and D-mode ultrasound images of 261 metastatic and 279 non-metastatic histopathologically confirmed LNs from 126 patients with head and neck squamous cell carcinoma. The YOLOv7-based B- and D-mode models were optimized using B- and D-mode training and validation images and their detection performance for metastatic LNs was evaluated using B- and D-mode testing images, respectively. The D-mode model's performance was comparable to that of radiologists and superior to that of residents' reading of D-mode images, whereas the B-mode model's performance was higher than that of residents but lower than that of radiologists on B-mode images. Thus, YOLOv7-based B- and D-mode models can assist less experienced residents in ultrasonographic diagnoses. The D-mode model could raise the diagnostic performance of residents to the same level as experienced radiologists.

Three Signs to Help Detect Sjögren's Syndrome: Incidental Findings on Magnetic Resonance Imaging and Computed Tomography.

This study aimed to retrospectively investigate the prevalence of Sjögren's syndrome (SS) among patients with ranulas, parotid cysts, or parotid calcifications; identify the characteristic magnetic resonance imaging (MRI) or computed tomography (CT) findings of the lesions associated with SS; and compare the SS disease stages among SS patients with the three lesion types. A total of 228 patients with the lesions were classified into SS, possible SS, and non-SS groups. The prevalence of SS among patients with ranulas, parotid cysts, or parotid calcifications was 16%, 24%, and 40%, and the rates of either SS or possible SS were 25%, 41%, and 64%, respectively. SS was associated with (i) ranulas: ≤17 mm; (ii) parotid cysts: bilateral and multiple; and (iii) parotid calcifications: in females, bilateral, multiple, parenchymal, and no coexisting calcifications in other tissues. SS patients with ranulas were significantly younger and had lower submandibular gland stage scores on MRI/CT than those with other lesions. Additionally, in 58% and 15% of SS patients with ranulas and parotid calcifications, respectively, detection of the lesions led to the diagnosis of primary SS. Therefore, recognizing the prevalence of SS among patients with these lesions and the findings associated with SS can help detect undiagnosed SS.

Relationship between drug holiday of the antiresorptive agents and surgical outcome of medication-related osteonecrosis of the jaw in osteoporosis patients.

A drug holiday of 3 months does not promote separation of sequestra and is not correlated with treatment outcomes after surgical therapy in osteoporosis patients who receive antiresorptive agents and who have medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive agents alone or in combination with immune modulators or antiangiogenic medications, in the absence of radiation exposure to the head and neck region. The effectiveness of surgical treatment for MRONJ has been reported, but the timing of the operation remains controversial. The purpose of this study was to clarify whether preoperative drug holidays of antiresorptive agents promote sequestrum separation and improve treatment outcomes in patients who receive low doses of antiresorptive agents. This retrospective study included 173 patients who received low-dose antiresorptive agents and underwent surgical therapy. The effects of a drug holiday on the separation of sequestra and treatment outcomes were analyzed using logistic and Cox regression analyses. Multivariate analysis revealed that administration of an antiresorptive agent for more than 4 years, a high number of lymphocytes, and an extensive osteolytic area were significantly correlated with separation of sequestra, but drug holiday did not promote sequestrum separation. Furthermore, a drug holiday of 90, 120 or 180 days did not show any improvement in treatment outcomes. The drug holiday of the antiresorptive agents for the treatment of MRONJ is unnecessary, and surgical therapy should be performed early.

Retrospective Analysis of Treatment Outcomes of Maxillary Sinusitis Associated with Medication-Related Osteonecrosis of the Jaw.

Although maxillary sinusitis often occurs in patients with medication-related osteonecrosis of the jaw (MRONJ) of the upper jaw, there have been few reports on the treatment and outcomes for maxillary sinusitis associated with maxillary MRONJ. This study aimed to retrospectively investigate the treatment outcomes of maxillary sinusitis in patients with MRONJ of the upper jaw. There were 34 patients diagnosed with maxillary MRONJ and sinusitis by preoperative computed tomography who underwent surgery in our institution between January 2011 and December 2019. Age, sex, primary disease, stage of MRONJ, class and administration period of an antiresorptive agent, corticosteroid administration, preoperative leukocyte count and serum albumin level, periosteal reaction, sinusitis grade, maxillary sinus surgical procedure, and treatment outcomes of MRONJ and sinusitis were examined. There were 7 male and 27 female patients (average age, 74.7 years). Complete healing of MRONJ was obtained in 29 of 34 patients (85.3%). Maxillary sinusitis resolved or improved in 21 patients (61.8%) but did not change or worsen in 13 patients (38.2%). We found that complete resection of necrotic bone with intraoperative irrigation of the maxillary sinus may provide good treatment outcomes for maxillary sinusitis associated with MRONJ, although our findings were not statistically significant owing to the small number of patients.

Relationship between Drug Holidays of Antiresorptive Agents and Surgical Outcomes in Cancer Patients with Medication-Related Osteonecrosis of the Jaw.

It is controversial as to whether the withdrawal of antiresorptive (AR) agents is necessary while treating medication-related osteonecrosis of the jaw (MRONJ). In this study, we investigated whether a drug holiday promoted sequestrum separation and improved the surgical outcomes of MRONJ patients with malignant tumors, who were undergoing high-dose AR therapy. In total, we included 103 MRONJ patients with malignant tumors as their primary disease who underwent surgery at Nagasaki University Hospital or Kansai Medical University Hospital from January 2009 to December 2020. We recorded the patients' age, sex, primary disease, MRONJ stage, type and administration period of the AR agent, presence of diabetes, corticosteroid use, drug holiday period, white blood cell count, serum albumin, serum creatinine, outcomes, and computed tomography findings. The relationships between a drug holiday and sequestrum separation, and between a drug holiday and outcome, were analyzed. Drug holidays of 60, 90, and 120 days were not significant factors of sequestrum separation and did not influence patients' surgical outcomes as per the univariate and multivariate analyses. MRONJ patients with cancer as their primary disease should be operated upon immediately and without drug holidays if their general condition permits surgery.

A case of periosteal fasciitis located in the mandible in a child.

Periosteal fasciitis (PF), a subtype of nodular fasciitis, is an uncommon benign soft-tissue mass that originates from the periosteum or tissues adjacent to bones. PF has rarely seen in children, especially involving in the mandible. This case report presents a rare case of PF originating from the periosteum of the mandible in an 11-year-old girl. She was referred to our hospital with fast-growing painless swelling in her left mandible. Computed tomography revealed an exophytic juxtacortical mass eroding the lower part of the left mandible and lower mandibular cortex with a periosteal reaction. The mass showed low signal intensity on T1-weighted magnetic resonance imaging (MRI) and high signal intensity on T2-weighted MRI. The apparent diffusion coefficient (ADC) of the lesion found to be moderate. Dynamic contrast-enhanced MRI revealed a gradual increment pattern in the central region of the mass. On 18F-fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT), relatively high 18F-FDG uptake was observed on the early scan and the 18F-FDG uptake was declined on the delayed scan. The clinical and conventional radiological findings of the mass were suggestive of malignancy. However, the findings of ADC and dynamic MRI and dual-time-point FDG-PET/CT favored benign etiology over malignant etiology. Histological and immunohistochemical findings along with reactive ossification of the periosteum confirmed the diagnosis of PF. Currently, comprehensive examinations, such as clinical, imaging, and histopathological examinations, are recommended for the definitive diagnosis of PF, while MRI and dual-time-point FDG-PET/CT could have a potential usefulness to differentiate from malignancy.

Imaging findings and treatment outcomes of a rare subtype of medication-related osteonecrosis of the jaw.

INTRODUCTION: In our previous study, we found a rare type of medication-related osteonecrosis of the jaw (MRONJ), which shows periosteal reaction (PR) at a site distant from osteolytic lesions or the extraction site (periosteal reaction dominant type, PRd type), even though the osteolytic lesions in the bone marrow are localized. The causes and treatment of MRONJ remain unclear; hence, this study aimed to describe the imaging and clinical features of the PRd type. MATERIALS AND METHODS: MRONJ patients who visited Nagasaki University Hospital between 2009 and 2020 and received conservative therapy as initial treatment were included in this study. The PR site, imaging findings, initial symptoms, outcome, and time to progression were examined. RESULTS: Among 59 MRONJ patients treated with conservative therapy, 38 did not show PR (PR- type), 15 showed PR near the osteolytic region (PR + type), and 6 had the PRd type. All patients with the PRd type had submental abscesses, and computed tomography (CT) images demonstrated PR on the lingual side of the anterior mandible. Osteolytic lesions progressed in 6/6 PRd type (100%), 5/15 PR + type (33.3%), and 2/38 PR- type (5.3%) patients. Time to progression for the osteolytic region on CT was short for the PRd type, at 56-148 days (median 79 days). CONCLUSION: Among the MRONJ types, the PRd type has a poor prognosis. Therefore, accumulating and analyzing more PRd cases in the future is warranted. This is the first report to describe the presence of this specific subtype of MRONJ.

Comparison of salivary gland MRI and ultrasonography findings among patients with Sjögren's syndrome over a wide age range.

OBJECTIVES: This retrospective study compared MRI and US findings among patients with SS over a wide age range. METHODS: Ninety patients with SS aged 8-84 years who had undergone both MRI and US examinations were divided into four groups according to age, as follows: <18 years (juvenile SS, JSS), 9 patients; 18-39 years, 12 patients; 40-69 years, 53 patients; >69 years, 16 patients. Imaging findings of parotid glands (PGs) and submandibular glands (SMGs) were compared among the four groups. Furthermore, the relationships within and between imaging findings and various clinical findings were examined. RESULTS: On MRI, patients with JSS commonly exhibited multiple high-intensity spots in the PGs on MR sialography and fat-suppressed T2-weighted imaging. With increasing SS group age, the frequencies and numbers of the high-intensity spots were lower. Fat areas on MRI and hyperechoic bands on US were rarely observed in the PGs and SMGs of patients with JSS, whereas they were more common in patients with adult SS. In addition, the presence of hyperechoic bands on US, the presence of fat areas on MRI, and decreased salivary flow were associated with one another. CONCLUSION: Salivary gland imaging findings in patients with JSS were characterized by punctate sialectasis, whereas those findings in patients with adult SS were characterized by fatty degeneration. Distinct findings in patients with JSS and adult SS are likely to reflect differences in glandular lesion stage. MRI and US are presumably useful for evaluation of glandular lesion severity during follow-up.

Periosteal reaction of medication-related osteonecrosis of the jaw (MRONJ): clinical significance and changes during conservative therapy.

PURPOSE: We previously reported that the periosteal reaction (PR) in medication-related osteonecrosis of the jaw (MRONJ) is a poor prognostic factor in surgical cases, but it is not clear how PR changes during conservative therapy. The purpose of this retrospective study was to compare computed tomography (CT) findings at the first visit and during follow-up visits in MRONJ patients subjected to conservative therapy and to investigate factors associated with the exacerbation of PR during conservative therapy. METHODS: Sixteen patients with MRONJ of the lower jaw who underwent conservative therapy and experienced a PR on CT images at the first visit and underwent CT examination again after 6 months or more were enrolled in the study. Clinical features and CT findings (extent of osteolytic lesion, extent of PR, type of PR, and changes during conservative treatment) were investigated. RESULTS: On the second CT scan, the osteolytic lesion improved in 4 patients, had not changed in 5, and deteriorated in 7, whereas the PR improved in 5 patients, had not changed in 4, and deteriorated in 7 patients. PR was significantly deteriorated in patients who continued to receive antiresorptive agents during conservative treatment and in patients with deteriorated osteolytic lesions. CONCLUSION: PR in MRONJ often expands during conservative therapy and the PR type progresses from the attached type to the gap type, and the irregular type, but discontinuation of antiresorptive agent may improve PR as well as osteolytic lesions.

Juvenile primary Sjögren's syndrome with ranula: is ranula a clinical sign that leads to early detection of Sjögren's syndrome?

Juvenile primary Sjögren's syndrome (pSS) is rare. Although recurrent parotitis is reported to be the most common symptom of juvenile pSS, the clinical symptoms and features of the syndrome are not well understood and are poorly defined. Here we report a rare case of juvenile pSS in a patient with plunging ranula. The patient had no symptoms other than swelling of the oral floor and had no symptoms of parotitis. Magnetic resonance imaging (MRI) revealed the diagnosis of plunging ranula. In addition, the findings of the bilateral parotid glands on MRI and subsequent ultrasonography (US) strongly suggested SS. On the basis of these imaging findings and laboratory data, a pediatric rheumatologist confirmed the diagnosis of juvenile pSS. The ranula may be one clinical sign of SS. However, this association remains generally unknown. Hypothesizing that SS might cause ranula development, we retrospectively investigated cases of patients with ranula who underwent MRI at our hospital. We found that many of these patients (> 20%) had characteristic findings strongly suggestive of SS. This result suggests that SS-induced changes in the sublingual glands are one cause of ranula formation. We think that ranula is a sign of early-stage SS. Therefore, patients with ranulae, whether adults or children, should undergo careful assessment of not only the sublingual glands but also the parotid and submandibular glands with MRI and/or US to investigate possible SS. This assessment may lead to early detection of SS.

Magnetic resonance perfusion and diffusion characteristics of granulomatous diseases mimic those of malignant lesions: six case reports.

The perfusion and diffusion properties of a tumor are important clues in evaluating its growth potential and predicting its histological type, such as benign or malignant. Tumor perfusion can be estimated by assessing time-dependent changes in the intratumoral levels of the contrast agent during dynamic contrast-enhanced magnetic resonance (MR) imaging, whereas tumor diffusion can be estimated by assessing intratumoral water diffusivity on diffusion-weighted MR imaging. Granulomatous diseases with different etiologies occur in various head and neck regions, including the mandible, maxillary sinus, salivary glands, and lymph nodes. However, the perfusion and diffusion properties of granulomatous diseases in the head and neck regions are not well documented. In this study, we assessed the time-signal intensity curves and apparent diffusion coefficients of six granulomatous diseases of various histological types that appeared in the soft tissues of the head and neck. Our data show that the perfusion and diffusion characteristics of granulomatous diseases mimic those of malignant diseases, highlighting the need for careful interpretation of MR perfusion and diffusion findings to distinguish between granulomatous diseases and cancers of the head and neck region. Clinicians should pay particular attention to blood examination and biopsy results when interpreting imaging findings.

Combined classification system based on ACR/EULAR and ultrasonographic scores for improving the diagnosis of Sjögren's syndrome.

We retrospectively evaluated the effectiveness of combined use of salivary gland ultrasonography (US) and the 2016 American College of Rheumatology/European League Against Rheumatic Disease (ACR/EULAR) classification criteria for improving the diagnostic efficiency in patients with Sjögren's syndrome (SS). A US-based salivary gland disease grading system was developed using a cohort comprising 213 SS or non-SS patients who fulfilled the minimum requirements for classifying SS based on the American-European Consensus Group (AECG) and ACR criteria. Using 62 SS or non-SS patients from the 213 patients and who had also undergone all the 5 examinations needed for the ACR/EULAR classification, we compared the diagnostic accuracy of various combinations of the ACR/EULAR and US classifications for diagnosing SS, using the clinical diagnosis of SS by rheumatologists as the gold standard. The ACR/EULAR criteria discriminated clinical SS patients with 77% and 79% accuracy for those with primary or secondary SS and for those with primary SS, respectively. However, the integrated score system of the ACR/EULAR and US classifications yielded 92% and 93% accuracy for these 2 SS patient groups, respectively, provided that US score of 3 was assigned to patients with US grade ≥2, and then patients with integrated threshold score of ≥5 were diagnosed as SS. Cross-validation also indicated improved accuracy of the integrated ACR/EULAR and US score system (91.9 and 93.0% for primary/secondary and primary SS patients, respectively) over that by the ACR/EULAR criteria alone. (74.2 and 86.0%, respectively). The integrated ACR/EULAR and US scoring system can improve the diagnosis of patients with clinical SS.

Arterial Spin Labeling Imaging for the Parotid Glands of Patients with Sjögren's Syndrome.

Sjögren's syndrome (SS) is characterized by hypofunction of the salivary and lacrimal glands. The salivary function is largely dependent upon the blood supply in the glands. However, the diseased states of the gland perfusion are not well understood. The arterial spin labeling (ASL) technique allows noninvasive quantitative assessment of tissue perfusion without the need for contrast agent. Here, we prospectively compared the perfusion properties of the parotid glands between patients with SS and those with healthy glands using ASL MR imaging. We analyzed salivary blood flow (SBF) kinetics of 22 healthy parotid glands from 11 volunteers and 28 parotid glands from 14 SS patients using 3T pseudo-continuous ASL imaging. SBF was determined in resting state (base SBF) and at 3 sequential segments after gustatory stimulation. SBF kinetic profiles were characterized by base SBF level, increment ratio at the SBF peak, and the differences in segments where the peak appeared (SBF types). Base SBFs of the SS glands were significantly higher than those of healthy glands (59.2 ± 22.8 vs. 46.3 ± 9.0 mL/min/100 g, p = 0.01). SBF kinetic profiles of the SS glands also exhibited significantly later SBF peaks (p < 0.001) and higher SBF increment ratios (74 ± 49% vs. 47 ± 39%, p = 0.04) than the healthy glands. The best SBF criterion (= 51.2 mL/min/100 mg) differentiated between control subjects and SS patients with 71% sensitivity and 82% specificity. Taken together, these results showed that the SS parotid glands were mostly hyperemic and the SS gland responses to gustatory stimulation were stronger and more prolonged than those of the healthy glands. The ASL may be a promising technique for assessing the diseased salivary gland vascularization of SS patients.

Salivary gland ultrasonography as a primary imaging tool for predicting efficacy of xerostomia treatment in patients with Sjögren's syndrome.

OBJECTIVE: To evaluate ultrasonography (US) grading of salivary gland disease as a predictor of treatment efficacy for impaired salivary function in xerostomia patients with or without Sjögren's syndrome (SS). METHODS: We retrospectively analysed the prognostic importance of salivary US grading in 317 patients (168 with SS and 149 without SS). US images of the parotid and submandibular glands in each patient were individually categorized into grades 0-4 based on the extent of damage to the gland; and the sum total grade of the two gland types on either side was assigned a US score of 0-8 for each patient. The relative importance of US score and demographic and clinical variables was assessed using stepwise multiple regression analysis after various durations of xerostomia treatment. RESULTS: Multiple regression analysis indicated that the baseline US score before treatment was the most important factor [standardized regression coefficient (ß) = -0.523, t-statistic (t) = -7.967, P < 0.001] in predicting negative outcomes in SS patients. Treatment duration (ß = 0.277, t = 4.225, P < 0.001) was also a significant but less important positive variable. On the other hand, US grading did not effectively predict treatment outcomes in non-SS patients, with treatment duration (ß = 0.199, t = 2.486, P = 0.014) and baseline salivary flow rate before treatment (ß = -0.172, t = -2.159, P = 0.032) being significant but weak predictors of positive and negative outcome, respectively. CONCLUSION: Salivary gland US grading may help to predict outcomes of treatment for impaired salivary function in patients with SS.

Reevaluation for clinical manifestations of HTLV-I-seropositive patients with Sjögren's syndrome.

BACKGROUND: The aim of the study was to reassess the prevalence and characteristics of human T lymphotropic virus type I (HTLV-I)-associated Sjögren's syndrome (SS) and SS in HTLV-I-associated myelopathy (HAM) based on the American European Consensus Group (AECG) criteria in HTLV-I endemic area, Nagasaki prefecture. METHODS: The 349 patients who underwent a minor salivary gland biopsy (MSGB) for suspected SS were retrospectively classified by AECG classification criteria and divided with or without anti-HTLV-I antibody. RESULTS: The HTLV-I data-available 294 patients were investigated. One hundred-seventy patients were classified as SS and 26.5 % were HTLV-I-seropositive. We have included 26 patients with HTLV-I-associated myelopathy (HAM) and 38.5 % were classified as having SS. The prevalences of ANA and anti-SS-A/Ro antibody of HAM + SS were significantly low compared to the HTLV-I asymptomatic carriers (AC) with SS and the HTLV-I-seronegative SS patients, although lacrimal dysfunction tended to be high in HAM + SS and significantly high in AC + SS patients compared with the patients with HTLV-I-seronegative SS. The focus scores of MSGB in the HAM + SS patients were similar to those of the AC + SS patients and the HTLV-I-seronegative patients with SS. Among the MSGB-positive patients, there was a low prevalence of ANA in the HAM + SS patients. Similar results were obtained in case of anti-SS-A/Ro or SS-B/La antibody. CONCLUSION: In HTLV-I endemic area, high prevalence of anti-HTLV-I antibody among SS as well as the characteristics of HAM + SS and AC + SS was still determined by AECG classification criteria.

Comorbid case of IgG4-related disease and primary Sjögren's syndrome.

A 63-year-old man with enlargement of the bilateral submandibular glands visited with elevated serum IgG4. A biopsy specimen showed plasma cell infiltration with more than 50% IgG4/IgG staining, suggesting the existence of IgG4-related disease (IgG4-RD). Positive anti-SS-A/Ro antibody and the labial salivary gland's biopsy suggested existence of primary Sjögren's syndrome (pSS). Administration of glucocorticoid improved the serum IgG4 level while reducing the submandibular gland lesions. Positive TUNEL staining suggested the coexistence of IgG4-RD and pSS.

Ultrasonography as an additional item in the American College of Rheumatology classification of Sjögren's syndrome.

OBJECTIVE: In this study we evaluated US as an additional classification item in the ACR classification of SS. METHODS: Of 581 patients classified as either SS (n = 364) or non-SS (n = 217) based on the minimum requirements of the American-European Consensus Group (AECG) classification, 184 patients (102 SS and 82 non-SS) who had scored two or more positive or two or more negative results according to the ACR criteria were selected. The AECG classification was used as the gold standard. A parotid and/or submandibular gland that was assigned a score ≥G1 was designated as SS positive. We evaluated US alone or with varying combinations of the ACR classification items in the diagnosis of SS. RESULTS: The ACR criteria diagnosed the 184 patients with 91% sensitivity, 90% specificity and 91% accuracy. US alone diagnosed the 184 ACR patients with 79% sensitivity, 90% specificity and 83% accuracy, which was comparable to the results of US diagnosis in the AECG cohort (81%, 86% and 83%, respectively). Incorporating the US criteria as an alternative to one of the three ACR classification items achieved 89-91% sensitivity, 87-96% specificity and 89% or 92% accuracy, which was comparable to that of the original ACR classification. Furthermore, kappa analysis indicated that the results of the original ACR and US-replaced ACR classifications matched completely (κ = 0.960-0.974). CONCLUSION: These results suggest that US can be used as an alternative to any of the three ACR classification items.