Systematic review and meta-analysis for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA). METHODS: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, 2 independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. RESULTS: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to csDMARD. Rituximab with and without concomitant csDMARDs showed similar efficacy to other bDMARDs in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. CONCLUSION: This systematic review provides latest evidence for the 2024 update of the JCR CPG for RA management.

Duodenal tuberculosis with gastric outlet obstruction: a case report of successful diagnosis and treatment, with review of literature.

BACKGROUND: Duodenal tuberculosis (TB) is extremely rare, and its diagnosis is challenging owing to the lack of specific symptoms and radiological or endoscopic findings. When it leads to gastric outlet obstruction (GOO), diagnosing it accurately and providing appropriate treatment is crucial. However, this is often overlooked. CASE PRESENTATION: A 35-year-old man presented with abdominal pain, fullness, vomiting, and weight loss. Upper gastrointestinal endoscopy and radiography revealed nearly pinpoint stenosis with edematous and reddish mucosa in the D1/D2 portion of the duodenum. Computed tomography (CT) showed the duodenal wall thickening, luminal narrowing, multiple enlarged abdominal lymph nodes, and portal vein stenosis. Conventional mucosal biopsy during endoscopy revealed ulcer scars. We initially suspected stenosis due to peptic ulcers; however, chest CT revealed cavitary lesions in both lung apices, suggesting tuberculosis. Due to the suspicion of duodenal TB and the need to obtain deeper tissue samples, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed. The tissue sample showed caseating granulomas with multinucleated giant cells, and acid-fast bacilli were positive by Ziehl-Neelsen staining. The patient was diagnosed with duodenal TB and subsequent GOO. Because the patient had difficulty eating, surgical intervention was prioritized over antitubercular drugs, and laparoscopic gastrojejunostomy was performed. The patient started an oral diet on the 3rd postoperative day and began antitubercular treatment immediately after discharge on the 11th day. During the 6th month of treatment, endoscopic examination revealed residual duodenal stenosis; however, the bypass route functioned well, and the patient remained asymptomatic. CONCLUSIONS: An aggressive biopsy should be performed to diagnose duodenal TB. EUS-FNA has proven to be a useful tool in this regard. Both nutritional improvement and antitubercular treatment were achieved early and reliably by performing laparoscopic gastrojejunostomy for duodenal TB with GOO.

Seasonal Influence on Development of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort Study Conducted at Multiple Institutions in Japan (J-CANVAS).

OBJECTIVE: To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season. RESULTS: A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season (P = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA (P < 0.001), but not in those with PR3-ANCA (P = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis. CONCLUSION: The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency.

Mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder: a case report.

BACKGROUND:  Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare. CASE PRESENTATION: We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy. CONCLUSIONS:  GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.

Diagnostic Performance of a Temporal Artery Biopsy for the Diagnosis of Giant Cell Arteritis in Japan-A Single-center Retrospective Cohort Study.

Objectives To investigate the sensitivity and specificity of a temporal artery biopsy (TAB) in the diagnosis of giant cell arteritis (GCA) in a single-center retrospective cohort in Japan. Methods A retrospective chart review was performed on consecutive patients who visited our hospital between April 2009 and October 2018 and underwent a TAB. The sensitivity and specificity were calculated for the three pathological standards for a TAB, predetermined according to the pathological criterion of the 1990 American College of Rheumatology (ACR) criteria: A) vasculitis characterized by predominant mononuclear cell infiltration; B) vasculitis with granulomatous inflammation; and C) vasculitis with multinucleated giant cells. We also analyzed the clinical parameters predicting the diagnosis of GCA and the impact of a diagnostic delay of ≥3 months on cardiovascular complications of GCA. Results Our study population was 16 cases in the GCA group and 13 in the non-GCA group. The sensitivity and specificity for Standard A of a TAB were 81% and 85%, respectively, while those for stricter Standards B or C were identical, at 75% and 100%, respectively. These pathological standards, but not any other parameters, significantly predicted the diagnosis. A diagnostic delay tended to cause cardiovascular complications (p=0.057). Conclusion The sensitivity and specificity of the pathological standards of a TAB were favorable in our cohort and were the only predictors for the diagnosis of GCA. Considering the possible impact of a diagnostic delay on cardiovascular complications, the early recognition and prompt initiation of glucocorticoid therapy is needed, even in Japan, where GCA is uncommon.

[A Case of Primary Testicular Mucinous Carcinoma].

A 68-year-old man presented withleft testicular painless swelling. His carbohydrate antigen 19-9 and carcinoembryonic antigen levels were elevated but his germ cell tumor markers were not high. Magnetic resonance imaging showed multiloculated cystic lesions with solid components in his left testis. Abdominal and chest computed tomography revealed multiple lung metastases, peritoneal dissemination and multiple lymph node metastases. Left high orchiectomy was performed. Histopathological examination demonstrated testicular mucinous carcinoma withsimilarity to gastric cancer. Since no tumor was found by the endoscopy of the upper gastrointestinal and the lower digestive tract, we diagnosed the patient with primary testicular mucinous carcinoma. Standard chemotherapy for gastric cancer, which consisted of tegafur, gimeracil and oteracil (TS-1) and cisplatin was administered for 16 months, and there was no progression of the disease. He died from testicular mucinous cancer 30 months after the diagnosis. In the literature, only 4 cases of testicular mucinous carcinoma have been reported. TS-1 and cisplatin are useful chemotherapeutic options for testicular mucinous carcinoma withmetastasis.

Syringomatous adenoma of the nipple: a case report.

INTRODUCTION: Syringomatous adenoma of the nipple is a very rare benign tumor. To the best of our knowledge, there are no reports of a syringomatous adenoma of the nipple metastasizing, although these tumors are known to infiltrate locally and to recur if not totally resected. CASE PRESENTATION: Our patient was a 41-year-old Japanese woman who complained of stiffness of her right nipple with abnormal discharge. Local resection of the tumor was performed. The pathological diagnosis was syringomatous adenoma of the nipple, and the resection margin was found to be positive. Accordingly, additional resection was recommended, but our patient did not allow another operation. After 1.5 years of careful follow-up, no local recurrence or distant metastasis has been observed. CONCLUSION: The optimal initial management of syringomatous adenoma of the nipple demands complete resection with histologically negative margins. However, from a cosmetic viewpoint, nipple-sparing resection could represent an alternative option for the treatment of syringomatous adenoma of the nipple.

Uncommon lymphoepithelial cyst with sebaceous glands of the pancreas.

CONTEXT: Lymphoepithelial cysts with sebaceous glands of the pancreas are extremely rare, with only 7 cases, including this case, published in English literature. CASE REPORT: We herein present the case of a 67-year-old Asian man who underwent a resection of a lymphoepithelial cyst of the pancreas during the follow up care for lung cancer. Fourteen years previously he underwent a right lower lobectomy at the right segment nine for lung cancer. A 20 mm mass in the body of the pancreas was identified by CT scan 4 years ago, and the diagnosis was intraductal papillary mucinous neoplasm (IPMN) at that time. Over a 5-year period, this mass grew to 42 mm without dilatation of the main pancreatic duct. The preoperative evaluation, including endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), indicated a cystic neoplasm with suspicion of malignancy. Intraoperative frozen section revealed a squamous-lined cyst accompanied by sebaceous glands without any malignant findings. Following this pathological finding, resection of the cyst was performed. Consequently, microscopic examination revealed that it was a lymphoepithelial cyst with sebaceous glands of the pancreas. CONCLUSIONS: Pancreatic lymphoepithelial cysts can be cured by conservative resection, but if they are asymptomatic and are diagnosed before surgery, no treatment is necessary. To our knowledge, this is the first ever published case of a lymphoepithelial cyst with sebaceous glands of the pancreas, which was found during the follow up care for lung cancer.

A case of CD45-negative diffuse large B-cell lymphoma in thyroid gland.

CD45, also referred to as the leukocyte common antigen (LCA), is selectively expressed on nucleated hematopoietic cells in healthy individuals. It is also widely expressed in various types of hematologic malignancies--although 10% of acute lymphoblastic leukemia and more than 50% of multiple myeloma have been reported to lack its expression. In this paper, we report a rare case of CD45-negative non-Hodgkin's lymphoma (NHL) that affected the thyroid gland.

CD20- and CD56-positive T-cell large granular lymphocyte leukemia in a human T-cell leukemia virus type 1 carrier.

A 60-year-old man was diagnosed with asymptomatic T-cell granular lymphocyte (T-LGL) leukemia in September 2006. He was serologically positive for human T-cell leukemia virus type 1 (HTLV-1). However, monoclonal integration of the HTLV-1 genome was not detected in the peripheral blood, suggesting that HTLV-1 did not contribute to the pathogenesis of T-LGL leukemia in the present case. Phenotypically, neoplastic cells of our case were CD3+, CD4*, CD8+, CD16-, CD56+, CD57*, and T-cell receptor (TCR) alphabeta+. They also coexpressed CD20 antigen with weak intensity. This represented a unique case of T-LGL leukemia showing a typical clinical and phenotypic features.

Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response.

Application of ultrasound-mediated destruction of microbubbles (US + Bubble) to skeletal muscle creates capillary ruptures leading to leakage of the cell components. We studied whether US + Bubble combined with bone-marrow-derived mononuclear cells (BM-MNCs) infusion enables the targeted delivery of endothelial-lineage cells into the myocardium and improves cardiac function of the cardiomyopathy model due to the paucity of neocapillary formation. Pulsed US was applied to the anterior chest of BIOTO2 cardiomyopathy hamsters for 90 s after the intravenous injection of microbubble (Optison) followed by infusion of BM-MNCs. Cardiac samples from US + microbubble + BM-MNCs (US + Bubble + BM), US + Bubble, US + BM without Bubble, and saline infusion control groups were analyzed 12 weeks after treatment. Labeled BM-MNCs transplanted by US + Bubble were found to be mainly localized in the microvessels, but not by US stimulation without microbubble (121.2 +/- 24.5 vs. 2.80 +/- 1.30 cells/mm2, P < 0.001). Capillary densities in US + Bubble + BM group were increased 1.7-fold (P < 0.05) over the control, and neither US + Bubble nor US + BM enhanced neocapillary formation. 99mTc-Tetrofosmin scintigraphy revealed that blood perfusion area in the US + Bubble + BM group was 48% greater than the control (P < 0.01). US + Bubble stimulation induces the expression of adhesion molecules (VCAM-1 and ICAM-1) in capillaries, and the US + Bubble-mediated supply of BM-MNCs increased the myocardial content of VEGF and bFGF. The left ventricular wt/body wt, area of cardiac fibrosis, and apoptotic cell numbers in the US + Bubble + BM group significantly (P < 0.05) decreased by 82%, 73%, and 64% relative to the control, respectively. The cardiac function in myopathic hamsters (assessed by fractional shortening) was markedly improved 36% (P < 0.05) by US + Bubble + BM treatment. Targeted delivery of BM-MNCs by US + Bubble to the myocardium of the cardiomyopathic hamster increased the capillary densities and regional blood flow and inhibited cardiac remodeling, resulting in the prevention of heart failure. This non-invasive cell delivery system may be useful as a novel efficient approach for angiogenic cell therapy to the myocardium.

A case of occult contralateral breast cancer incidentally detected by contrast-enhanced MRI; report of a case with review of literature.

We encountered a case of occult contralateral breast cancer, previously undetected by conventional imaging such as mammography (MMG) and ultrasonography (US), but incidentally detected by contrast-enhanced magnetic resonance imaging (CE-MRI). We present it here with a review of the literature. A 67-year-old Japanese woman was referred to our hospital in October 2000 because of a 1.5 cm right breast lump detected in a medical checkup. MMG, US and fine needle aspiration cytology revealed a cancerous lesion during the right breast. No mass lesion was palpable nor was any detected by MMG or US in the left breast. Bilateral breast CE-MRI was performed for more detailed evaluation. Consequently, an occult contralateral breast cancerous lesion was detected incidentally by CE-MRI, with the images showing rapid initial enhancement of time to signal intensity curves. Before surgery, bilateral breast lesions were diagnosed as invasive ductal carcinoma by open biopsy. She underwent bilateral breast conserving surgery with bilateral axillary lymph node dissection. The postoperative course was uneventful and no recurrence has been noted as of January 18th, 2004. CE-MRI of the contralateral breast should be of value as a routine screen in those patients with a known or suspected malignancy in one breast considering the limits of breast cancer detection by such conventional modalities as MMG and US.

Predictive value of the time-intensity curves on dynamic contrast-enhanced magnetic resonance imaging for lymphatic spreading in breast cancer.

PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a promising diagnostic modality in various breast cancer treatments. However, little is known about the correlation between the pattern of time to signal intensity curves (TIC) on the CE-MRI and clinicopathologic features. This study was designed to investigate these correlations and evaluate the predictive value of TIC on CE-MRI in order to identify high-risk patients. METHODS: Between 2001 and 2003, 101 lesions were evaluated to detect malignancy on CE-MRI in 101 women who were suspected of having breast tumors based on either clinical findings or conventional imaging studies. Moreover, the clinicopathologic findings were compared with the pattern of TIC for the 69 surgically treated malignant lesions. RESULTS: In detecting malignancy, the sensitivity, specificity, and accuracy were 78.7%, 88.5%, and 81.2%, respectively, in the 101 breast lesions. Especially for the 69 surgically treated malignant lesions, in comparison with breast cancer tumors with the benign pattern of TIC, the breast cancer tumors with a malignant pattern were found more frequently in lymphatic invasion (P < 0.01) and lymph node metastasis (P < 0.005), although no statistical correlation regarding the histological type, tumor size, vascular invasion, extensive intraductal component, hormone receptor status, or pathological stage was noted between the two groups. According to a logistic regression model, lymph node metastasis was found to be a significant independent variable. CONCLUSION: The pattern of TIC could be used to predict lymphatic spreading associated with lymph node metastasis prior to surgery as well as to detect malignancy. Therefore, a more detailed evaluation should be made to identify the presence of lymphatic spreading in patients with a malignant pattern of TIC.

Comparison of intraductal spread on dynamic contrast-enhanced MRI with clinicopathologic features in breast cancer.

OBJECTIVE: Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a new diagnostic technology in various breast cancer treatments. However, little is known about the correlation between intraductal spread on CE-MRI and clinicopathologic features. This study was designed to evaluate these correlations for the surgical planning of breast cancer. METHODS: Twenty-six breast cancer lesions (in 26 female patients) treated by breast conserving surgery between March 2001 and March 2003 were evaluated retrospectively. CE-MRI was performed with a 1.5 T unit using a dedicated bilateral breast coil. RESULTS: In detecting intraductal spread of breast cancer, the sensitivity, specificity and accuracy of CE-MRI were 82.4%, 60.0% and 77.3%, respectively. On mammography (MMG), these were 21.1%, 100.0% and 42.3%, respectively. Therefore, CE-MRI has a higher sensitivity and accuracy, although with a lower specificity than MMG. Compared with breast cancer lesions without intraductal spread on CE-MRI, lesions with intraductal spread on CE-MRI were found more frequently in larger-sized tumors (P = 0.0088). CONCLUSION: Preoperative evaluation for intraductal spread by CE-MRI should be more useful than by MMG for breast cancer. When making the surgical decision regarding excision range, particular attention should be paid to this consideration for patients with larger-sized cancer tumors.