A case of pulmonary sarcoidosis with usual interstitial pneumonia-like lesions distributed predominantly in the lower lung fields]

In 2000, in a 75-year-old man, nodular and reticular opacities were detected in both lower lung fields. He was admitted to our hospital for further examination of these abnormal shadows. Bronchoscopic examination revealed pulmonary sarcoidosis. Prednisolone was prescribed because cardiac sarcoidosis was diagnosed as a clinical complication. In April 2002, the patient visited our hospital for dyspnea on effort. Chest radiography and computed tomography showed nodular and reticular opacities in the right upper lobe, and video-assisted thoracoscopic surgery was performed on the basis of a histological diagnosis. The histological findings of the biopsied specimens revealed a lesion of the type seen in usual interstitial pneumonia, whereas non-caseous granulomas were not detected. His symptoms and chest radiographic findings improved and stabilized with prednisolone and azathioprine. In the present case of pulmonary sarcoidosis, the reticular and nodular opacities predominantly distributed in both lower lung fields, and the histological findings obtained by video-assisted thoracoscopic surgery showed a usual interstitial pneumonia-like lesion. These findings may assist in the understanding of the process of development of pulmonary sarcoidosis.     

Pulmonary metastasectomy for pulmonary metastasis of breast cancer has a limited prognostic impact: a multi-institutional retrospective analysis

BackgroundPulmonary metastasectomy (PM) for breast cancer-derived pulmonary metastasis is controversial. This study aimed to assess the prognostic factors and implication of PM for metastatic breast cancer using a multi-institutional database.MethodsClinical data of 253 females with pulmonary metastasis of breast cancer who underwent PM between 1982 and 2017 were analyzed retrospectively.ResultsThe median patient age was 56 years. The median follow-up period was 5.4 years, and the median disease-free interval (DFI) was 4.8 years. The 5- and 10-year survival rates after PM were 64.9% and 50.4%, respectively, and the median overall survival was 10.1 years. Univariate analysis revealed that the period of PM before 2000, a DFI <36 months, lobectomy/pneumonectomy, large tumor size, and lymph node metastasis were predictive of a worse overall survival. In the multivariate analysis, a DFI <36 months, large tumor size, and lymph node metastasis remained significantly related to overall survival. The 5- and 10-year cancer-specific survival rates after PM were 66.9% and 54.7%, respectively, and the median cancer-specific survival was 13.1 years. Univariate analyses revealed that the period of PM before 2000, DFI <36 months, lobectomy/pneumonectomy, large tumor size, lymph node metastasis, and incomplete resection were predictive of a worse cancer-specific survival. Multivariate analysis confirmed that a DFI <36 months, large tumor size and incomplete resection were significantly related to cancer-specific survival.ConclusionsAs PM has limited efficacy in breast cancer, it should be considered an optional treatment for pulmonary metastasis of breast cancer.     

Hemodialysis as a Risk Factor for Ceftriaxone‐Associated Pseudolithiasis in Adults

Ceftriaxone‐associated biliary pseudolithiasis is common among children; however, there are only a few reports of pseudolithiasis in adult patients on HD. This retrospective cohort study included 278 adult patients on ceftriaxone therapy from 1 February 2016 to 1 September 2018. Pseudolithiasis was defined as a new development of sludge or stones in the gallbladder within 60 days of ceftriaxone therapy. After excluding patients with preexisting gallstones and a history of cholecystectomy, 113 patients on maintenance HD, and another 98 patients were enrolled as the HD and control group, respectively. Thirteen patients developed pseudolithiasis. Its incidence was significantly higher in the HD group than that in the control group. Multivariate logistic regression analyses showed that development of pseudolithiasis was significantly associated with HD and ceftriaxone dose. Therefore, HD in patients receiving ceftriaxone therapy appears to be associated with a risk of pseudolithiasis. These findings highlight the need for careful follow‐up.     

Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P?=?0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P?=?0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P?=?0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P?=?0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.     

A case of bleeding duodenal ulcer with pemphigus vulgaris during steroid therapy

We report a rare case of bleeding duodenal ulceration in the different form of pemphigus vulgaris (PV). A 52-year-old female was diagnosed with acute pharyngitis and administered methylprednisolone. After several days, melena and many blisters were noted on her body. Endoscopy revealed blood oozing from the second part of a duodeneal ulcer around the major duodenal papilla. After initial endoscopic hemostasis, we observed a large regional, shallow duodenal ulcer. The blisters were suspected to represent the Nikolsky’s sign. The histological findings of her skin were characterized by suprabasal acantholysis and mixed inflammatory cell infiltrates, including scattered eosinophils. There were no other significant findings on skin biopsy or by direct immunofluorescence. Enzyme-linked immunosorbent assay showed an elevated titer of anti-desmoglein 3 autoantibodies in her serum, and the patient was finally diagnosed with mucosal-dominant PV. Although we performed multiple biopsies from the esophagus, stomach and duodenum, the samples did not contain significant findings to enable us to distinguish from pemphigus vulgaris. Corticosteroids remain an essential component of PV treatment. When clinicians encounter PV development during steroid therapy, upper gastrointestinal complications should be considered and diagnostic endoscopy conducted.     

The immunobiology of colitis and cholangitis in interleukin-23p19 and interleukin-17a deleted dominant negative form of transforming growth factor beta receptor type ii mice

Dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) mice, expressing a dominant negative form of TGFβ receptor II under control of the CD4 promoter, develop autoimmune colitis and cholangitis. Deficiency in interleukin (IL)-12p40 lead to a marked diminution of inflammation in both the colon and the liver. To distinguish whether IL-12p40 mediates protection by the IL-12 or IL-23 pathways, we generated an IL-23p19(-/-) dnTGFβRII strain deficient in IL-23, but not in IL-12; mice were longitudinally followed for changes in the natural history of disease and immune responses. Interestingly, IL-23p19(-/-) mice demonstrate dramatic improvement in their colitis, but no changes in biliary pathology; mice also manifest reduced T-helper (Th)17 cell populations and unchanged IFN-γ levels. We submit that the IL-12/Th1 pathway is essential for biliary disease pathogenesis, whereas the IL-23/Th17 pathway mediates colitis. To further assess the mechanism of the IL-23-mediated protection from colitis, we generated an IL-17A(-/-) dnTGFβRII strain deficient in IL-17, a major effector cytokine produced by IL-23-dependent Th17 cells. Deletion of the IL-17A gene did not affect the severity of either cholangitis or colitis, suggesting that the IL-23/Th17 pathway contributes to colon disease in an IL-17-independent manner. These results affirm that the IL-12/Th1 pathway is critical to biliary pathology in dnTGFβRII mice, whereas colitis is caused by a direct effect of IL-23. (HEPATOLOGY 2012).     

Reversal of slow growth and heartbeat through the restoration of mitochondrial function in clk-1-deficient mouse embryos by exogenous administration of coenzyme Q10

The longevity gene clk-1/coq7 encodes an enzyme that is essential for the biosynthesis of coenzyme Q (CoQ) in mitochondria and regulates the lifespan and behavioral timing in Caenorhabditis elegans and the chronological lifespan in fission yeast. However, whether the mammalian clk-1/coq7 ortholog (clk-1) regulates these phenotypes in mammals remains to be fully evaluated due to the embryonic lethality of clk-1-deficient (clk-1(-/-)) mice. To investigate whether clk-1 regulates biological functions, such as growth and heartbeat, through CoQ in mouse embryos, we cultivated the cells and hearts of clk-1(-/-) mouse embryos at embryonic day 10.5 (E10.5) for at least 10 days in the presence of fetal bovine serum. In embryonic cells, cardiomyocytes, and hearts, the growth and heart rates were significantly slowed in clk-1(-/-) compared with wild-type or heterozygous mouse tissues. Moreover, frequent apoptosis and a significant reduction in mitochondrial functions, including membrane potential and ATP production, were observed in the clk-1(-/-) cells and hearts. The slowed growth and heart rates and the reduced mitochondrial function of clk-1(-/-) embryonic cells and hearts in culture were almost completely rescued by the administration of exogenous CoQ(10). The results indicate that clk-1 regulates growth and heart rates through CoQ-mediated mitochondrial functions in mouse embryos.