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Background Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) of the pancreas are extremely rare. Their pathogenesis and molecular landscape are largely unknown. Here, we report a case of mixed pancreatic intraductal papillary mucinous neoplasm (IPMN) and well-differentiated neuroendocrine tumor (NET) and identify its genetic alterations by next-generation sequencing (NGS). Case presentation A fifty-year-old male was admitted into the hospital for evaluation of a pancreatic lesion detected during a routine examination. Abdominal ultrasound indicated a hypoechoic mass of 2.6 cm at the head of the pancreas. Malignancy was suspected and partial pancreatectomy was performed. Thorough histopathological examination revealed a mixed IPMN-NET. In some areas, the two components were relatively separated, whereas in other areas IPMN and NET grew in a composite pattern: The papillae were lined with epithelial cells of IPMN, and there were clusters of NET nests in the stroma of papillary axis. NGS revealed shared somatic mutations (KRAS, PCK1, MLL3) in both components. The patient has been uneventful 21 months after the surgery. Conclusions Our case provides evidence of a common origin for mixed IPMN-NET with composite growth features. Our result and literature review indicate that KRAS mutation might be a driver event underlying the occurrence of MiNEN. We also recommend the inclusion of mixed non-invasive exocrine neoplasms and neuroendocrine neoplasms into MiNEN.

Background Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement. Methods We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without. Results The two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15). Conclusions Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn’s disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.

Chronic active Epstein–Barr virus infective enteritis (CAEBV enteritis) is rare and has not been well described yet. Therefore, we reported the clinicopathologic features of 11 patients with chronic active Epstein–Barr virus infective enteritis and their differences from inflammatory bowel disease. The major clinical presentations of chronic active Epstein–Barr virus infective enteritis were intermittent fever over 39 °C (100%), diarrhea (73%), abdominal pain (64%), lymphadenopathy (64%), splenomegaly (64%), and hepatomegaly (27%). The main endoscopic findings included numerous shallow, small, and irregular ulcers, mainly involving colon and small intestine together, no cobble-like appearance, and longitudinal ulcers. Compared to inflammatory bowel disease patients, the frequency of intermittent fever, hepatomegaly, splenomegaly, lymphadenopathy, the value of C-reactive protein, and serum Epstein–Barr virus DNA (EBV DNA) were significantly higher in chronic active Epstein–Barr virus infective enteritis patients (p

Summary Background Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial. Methods This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18–75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes—intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only—are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov , NCT02619942 . Study recruitment is complete, and follow-up is ongoing. Findings Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, −2·2% [95% CI −7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I–II complications were similar between groups (91 [18%] vs 92 [18%], difference, −0·0% [95% CI −4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III−IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], −2·2% [−4·1 to −0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes. Interpretation Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons. Funding The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences.

BackgroundCarcinogenesis is a severe consequence of chronic ulcerative colitis. We investigated the somatic mutations and pathway alterations in ulcerative colitis–associated colorectal cancer (CRC) in Chinese patients compared with sporadic CRCs to reveal potential therapeutic targets in ulcerative colitis–associated CRC.MethodsWhole exome sequencing was performed on archival tumor tissues and paired adjacent nondysplastic mucosa from 10 ulcerative colitis–associated CRC patients at a high risk of carcinogenesis. Genomic alteration profiles from 223 primary CRCs from The Cancer Genome Atlas served as sporadic CRC controls. A meta-analysis was performed to investigate differences in major genetic mutations between ulcerative colitis–associated and Crohn’s disease–associated CRCs.ResultsWe identified 44 nonsilent recurrent somatic mutations via whole exome sequencing, including 25 deleterious mutations involved in apoptosis and the PI3K-Akt pathway (COL6A3, FN1), autophagy (ULK1), cell adhesion (PODXL, PTPRT, ZFHX4), and epigenetic regulation (ARID1A, NCOR2, KMT2D, NCOA6, MECP2, SUPT6H). In total, 11 of the 25 mutated genes significantly differed between ulcerative colitis–associated CRC and sporadic CRC (APC, APOB, MECP2, NCOR2, NTRK2, PODXL, RABGAP1, SIK3, SUPT6H, ULK1, USP48). Somatic TP53 mutations occurred in 33% of ulcerative colitis–associated CRCs. Subsequent meta-analysis revealed distinct mutation profiles for Crohn’s disease– and ulcerative colitis–associated CRCs. Mutations involving the NF-kB pathway and epigenetic regulation were more common in ulcerative colitis–associated CRCs than in sporadic CRCs.ConclusionDistinct genomic alteration profiles of deleterious somatic mutations were found in ulcerative colitis–associated and sporadic CRCs. Mutations of epigenetic regulators, such as KMT2D and NCOA6, were common, suggesting an epigenetic pathomechanism for colitis-associated carcinoma in Chinese patients.

Hemangiopericytoma (HPC) is a rare tumor originating from pericapillary cells. Rarely found in the central nervous system, it is extremely rare in the spinal canal. Because of the low incidence of this tumor, its radiographic features and clinical manifestations have not been extensively studied and reported, therefore, it is often misdiagnosed as a schwannoma or spinal meningioma. We describe an unexpected HPC in a 35-year-old woman who was admitted to the Peking Union Medical College Hospital with a severe backache, sensory abnormalities, and muscle weakness. Magnetic resonance imaging showed an enhancing lesion at T6-7 with severe compression of the spinal cord. Gross total resection was achieved, and subsequently, a marked neurologic improvement was observed. The diagnosis of primary extradural HPC in our patient was confirmed based on postoperative histopathology and immunohistochemistry. Neither recurrence nor metastasis of the tumor was found during the 14-month follow-up, which did not include radiotherapy. To describe the demography, radiologic features, treatment, and prognosis of spinal HPC, a comprehensive literature review was performed and 105 cases of primary spinal HPC from 1958 to 2017 were collected from 39 articles. Although rare, HPC should be considered in the differential diagnosis of intraspinal lesions. Immunohistologic examination is of decisive importance in making the diagnosis. Adequate surgical resection, when feasible, is the first choice of treatment for all cases of HPC; however, the outcomes of radiotherapy and chemotherapy have yet to be determined. Individualized treatment combined with long-term follow-up for each patient is recommended.

IL-1R–associated kinase (IRAK)-M regulates lung immunity during asthmatic airway inflammation. However, the regulatory effect of IRAK-M differs when airway inflammation persists. A positive association between IRAK-M polymorphisms with childhood asthma has been reported. In this study, we investigated the role of IRAK-M in the susceptibility to adult-onset asthma and in chronic airway inflammation using an animal model. Through genetic analysis of IRAK-M polymorphisms in a cohort of adult-onset asthma patients of Chinese Han ethnicity, we identified two IRAK-M single nucleotide polymorphisms, rs1624395 and rs1370128, genetically associated with adult-onset asthma. Functionally, the top-associated rs1624395, with an enhanced affinity to the transcription factor c-Jun, was associated with a higher expression of IRAK-M mRNA in blood monocytes. In contrast to the protective effect of IRAK-M in acute asthmatic inflammation, we found a provoking impact of IRAK-M on chronic asthmatic inflammation. Following chronic OVA stimulation, IRAK-M knockout (KO) mice presented with significantly less inflammatory cells, a lower Th2 cytokine level, a higher IFN-γ concentration, and increased percentage of Th1 cells in the lung tissue than wild type mice. Moreover, lung dendritic cells (DC) from OVA-treated IRAK-M KO mice expressed a higher percentage of costimulatory molecules PD-L1 and PD-L2. Mechanistically, in vitro TLR ligation led to a greater IFN-γ production by IRAK-M KO DCs than wild type DCs. These findings demonstrated a distinctive role of IRAK-M in maintaining chronic Th2 airway inflammation via inhibiting the DC-mediated Th1 activation and indicated a complex role for IRAK-M in the initiation and progression of experimental allergic asthma.

Purpose: This study aimed to determine whether detecting elastic fibers in tumor stroma (EFTS) could be used as a new method for predicting the prognosis of gastric cancer (GC) patients. Materials and Methods: EFTS expression was determined by histochemistry in 160 gastric cancer patients who underwent gastrectomy. Based on the staining results, the patients were divided into three groups according to their EFTS expression level: low (n=57), moderate (n=50) and high (n=53). The clinicopathological data and 6-year survival data were analyzed among different EFTS groups. Results: The expression of EFTS was closely related to lymphovascular invasion (P=0.010), blood transfusion in operation (P＜0.001), recurrence rate (P＜0.001) and motility (P＜0.001). High expression of EFTS was also correlated with recurrence-free survival (RFS) and overall survival (OS) in gastric cancer patients by Kaplan–Meier curve (P＜0.001 for RFS and P＜0.001 for OS, respectively). Conclusions: Multivariate analysis showed EFTS was an independent prognostic factor for RFS and OS. In conclusion, detecting EFTS to predict the prognosis of gastric cancer patients is effective and highly feasible.

Remote sensing image retrieval(RSIR), which aims to efficiently retrieve data of interest from large collections of remote sensing data, is a fundamental task in remote sensing. Over the past several decades, there has been significant effort to extract powerful feature representations for this task since the retrieval performance depends on the representative strength of the features. Benchmark datasets are also critical for developing, evaluating, and comparing RSIR approaches. Current benchmark datasets are deficient in that 1) they were originally collected for land use/land cover classification and not image retrieval, 2) they are relatively small in terms of the number of classes as well the number of sample images per class, and 3) the retrieval performance has saturated. These limitations have severely restricted the development of novel feature representations for RSIR, particularly the recent deep-learning based features which require large amounts of training data. We therefore present in this paper, a new large-scale remote sensing dataset termed "PatternNet" that was collected specifically for RSIR. PatternNet was collected from high-resolution imagery and contains 38 classes with 800 images per class. We also provide a thorough review of RSIR approaches ranging from traditional handcrafted feature based methods to recent deep learning based ones. We evaluate over 35 methods to establish extensive baseline results for future RSIR research using the PatternNet benchmark., Comment: 49 pages

Asthma is an airway epithelium disorder involving allergic lung inflammation. IL-1 receptor–associated kinase M (IRAK-M) is a negative regulator of Toll-like receptor (TLR) signaling on airway epithelial cells and macrophages, and it is known to limit the overproduction of cytokines during the inflammatory process. However, the direct role of IRAK-M in asthma pathogenesis is unclear. In the present study, we found a significant elevation of IRAK-M expression in mouse lungs after ovalbumin (OVA) exposure. Compared with wild-type mice, IRAK-M knockout (KO) mice responded to OVA challenge with significantly worse infiltration of airway inflammatory cells, greater airway responsiveness, higher proinflammatory cytokine levels in lung homogenates, and more prominent T-helper cell type 2 (Th2) and Th17 deviation. OVA exposure also induced higher activities of dendritic cells (DCs) and macrophages from IRAK-M KO mouse lungs. Furthermore, adoptive transfer of either IRAK-M KO bone-marrow–derived DCs or macrophages into wild-type mice aggravated OVA-induced airway inflammation. In vitro experiments showed that IRAK-M KO naive CD4(+) T cells were more prone to differentiate into Th17 cells, but not regulatory T cells. Consistently, activation of IκBζ was significantly increased in the absence of IRAK-M, facilitating Th17 polarization. These findings suggest that IRAK-M plays a crucial role in the regulation of allergic airway inflammation by modifying the function of airway epithelia, DCs, and macrophages, and the differentiation of naive CD4(+) T cells. Modulation of IRAK-M may provide a novel target for the control of asthma.

Conventional endoscopy and endoscopic ultrasonography (EUS) are used to estimate the invasion depth of early-stage gastric cancers (EGCs), but estimates made by either technique are often inaccurate. We developed a model to determine the invasion depth of EGCs using conventional endoscopy and EUS findings, with pathology results as the reference. We performed a retrospective study of 195 patients (205 lesions) diagnosed with gastric cancers who underwent endoscopy and EUS followed by resection. Based on pathology analyses, lesions (n = 205) were assigned to categories of: mucosa invasion or minute invasion into the submucosal layer less than 500 μm from the muscularis mucosae (M-SM1) or penetration of 500 μm or more (≥SM2). The lesions were randomly assigned to derivation (138 lesions) and validation sets (67 lesions). A depth predictive model was proposed in the derivation set using multivariate logistic regression analyses. The discriminative power of this model was assessed in both sets. Remarkable redness (OR 5.42; 95% CI 1.32–22.29), abrupt cutting of converging folds (OR 8.58; 95% CI 1.65–44.72), lesions location in the upper third of the stomach (OR 10.26; 95% CI 2.19–48.09), and deep invasion based on EUS findings (OR 16.53; 95% CI 4.48–61.15) significantly associated with ≥SM2 invasion. A model that incorporated these 4 variables discriminated between M-SM1 and ≥SM2 lesions with the area under the ROC curve of 0.865 in the derivation set and 0.797 in the validation set. In the derivation set, a cut-off score of 8 identified lesions as ≥SM2 with 54% sensitivity and 97% specificity. The model correctly predicted the invasion depth 89.86% of lesions; it overestimated the depth of 2.17% of lesions. We developed a model to identify EGCs with invasion depth ≥SM2 based on endoscopy and EUS findings. This model might reduce overestimation of gastric tumor depth and prevent unnecessary gastrectomy.

The early detection and accurate histopathological diagnosis of gastric cancer increase the chances of successful treatment. The worldwide shortage of pathologists offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. Here, we report a clinically applicable system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieves a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset with 3,212 whole slide images digitalized by three scanners. We show that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrate that our system performs robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios., The early detection and accurate histopathological diagnosis of gastric cancer are essential factors that can help increase the chances of successful treatment. Here, the authors report on a digital pathology tool achieving high performance on a real world test dataset and show that the system can aid pathologists in improving diagnostic accuracy.

e16553 Background: The dynamics of the cancer genome and T-cell receptor (TCR) repertoire are largely unclear during the development of gastric cancer, especially in the early stage. In this study, we studied the characteristics of genome and tumor microenvironment changes chronologically in 15 early gastric cancer (EGC) patients and illustrated their influence on carcinogenesis. Methods: 75 gastric tissues including precancerous lesions, cancer lesions and paired reference gastric samples, and 29 peripheral blood samples were obtained chronologically from 15 patients. All the lesions were categorized into 3 groups according to its pathology type (group1: inflammation or intestinal metaplasia, group 2: low-grade dysplasia (LGD), group 3: EGC). Deep sequencing of whole-exome and CDR3 chain of TCR of each sample was performed. Tumor mutation burden (TMB), TCR repertoire diversity and clonality were evaluated based on the sequencing data. Results: Heterogeneity existed in cancer genome and TCR repertoire among different patients. During carcinogenesis, TMB increased at first and then decreased, reaching its peak at LGD, which was different from what we have known from other advanced cancer. A detailed analysis showed that only part of the driver gene mutations maintained in this process. Compared with T cells infiltrated in reference samples, tumor-infiltrating T cells shared more clones with peripheral blood T cells. Diversity and clonality of TCR repertoire didn’t show significant change with the development of cancer (Shannon index: group 1 = 6.32, group 2 = 6.06, group 3 = 6.09, p = 0.836; Clonality: group 1 = 0.19, group 2 = 0.19, group 3 = 0.17, p = 0.374). Some CDR3 clones appeared in early-stage and maintained during the carcinogenesis process. Conclusions: Our research is the first to analyze the cancer genome and TCR repertoire changes from both the spatial and temporal perspectives during the development of early gastric cancer. Somatic mutations appeared in the very early stage of gastric cancer and may induce the immune microenvironment changes in gastric mucosa.

Oncogenic fusions are rare in colorectal carcinomas, but may be important for prognosis and therapy. An effective strategy for screening targetable oncogenic fusions in colorectal carcinomas is needed. Here, we investigate molecular genetic alterations in colorectal carcinomas based on their DNA mismatch repair status, and to effectively screen for targetable oncogenic fusions in colorectal carcinomas. In this retrospective study, the initial cohort included 125 consecutive mismatch repair-deficient and 238 randomly selected mismatch repair-proficient colorectal carcinomas diagnosed between July 2015 and December 2017 at Peking Union Medical College Hospital. Targeted sequencing was performed. MLH1 promoter hypermethylation analysis was further employed for subgrouping dMMR colorectal carcinomas. Clinicopathological characteristics, molecular features, and survival outcome of colorectal carcinomas harboring oncogenic fusions were assessed. A multicenter cohort comprised of 227 colorectal carcinomas with dual loss of MLH1/PMS2 was used to validate the efficacy of the proposed screening strategy for oncogenic fusions. Of the 363 patients in the initial cohort, 11(3.0%) harbored oncogenic fusions and were all mismatch repair-deficient colorectal carcinomas with hypermethylated MLH1 and wild-type BRAF and KRAS, comprising 55% (11/20) of this subgroup. These patients with oncogenic fusions showed poorer 3-year cancer-specific survival compared with other Stage III/IV mismatch repair-deficient colorectal carcinoma patients (40% vs. 97%), and significantly higher CD274(PD-L1) expression in tumor cells compared with other dMMR colorectal carcinoma patients (46% vs. 6.1%, P

A 17-year-old adolescent boy with a history of hypoproteinemia underwent Ga-NEB PET/MRI to evaluate possible lymphatic disorders suggested by FDG PET/CT imaging. The images revealed multiple lesions with increased Ga-NEB uptake and high signal on T2-weighted images, consistent with likely lymphatic disorder. Histopathological examination from biopsied specimen confirmed lymphangioma.

An increasing number of drugs including monoclonal antibodies and small molecules, either anti-inflammatory or immunity-enhancing, have been developed to treat human diseases and the number of medications in these classes is likely to expand in the future. The two most commonly used categories of such therapies are the anti-inflammatory group (anti- tumor necrosis factor (TNF) α, anti-interleukins/interleukin receptors, and anti-integrin bodies) and the anti-tumoral agents (immune checkpoint inhibitors, anti-CD20, and anti-endothelial growth factor). Although the anti-inflammatory biologics have brought about a revolutionary effect in the management of a variety of autoimmune disorders including rheumatologic diseases, inflammatory bowel disease, and inflammatory dermatological diseases, their ability to induce colitis in patients without a prior history of colitis or exacerbate quiescent colitis has been increasingly and unexpectedly recognized. While the use of immune-augmenting monoclonal antibody therapies results in a significant survival benefit in a subset of patients with malignancies, these monoclonal antibodies also have the ability to cause colitis through an apparent autoimmune mechanism. Colitis associated with these medications may demonstrate multiple histologic patterns including increased apoptosis (graft versus host disease (GVHD)-like), autoimmune enteropathy pattern, acute colitis pattern, ischemic colitis, inflammatory bowel disease pattern, either ulcerative colitis-like, Crohn's disease-like, or fulminant colitis-like. In addition, anti-inflammatory biologics are known to cause or reactivate latent infections such as tuberculosis and increase the risk for malignancies including high-grade lymphomas as well as indolent lymphoproliferative disorders. Thus, the differential diagnosis for colitis in patients receiving therapeutic anti-inflammatory biologics or anti-tumoral agents can be broad. Optimal diagnosis and treatment requires a multidisciplinary approach. This review aims to provide an overview of the literature on the clinical features, histology, and treatment of these newly recognized anti-inflammatory biologic and anti-tumoral immune therapy-induced colitises and hopes this outlines will raise the vigilance of all clinicians of these entities.

Objective The aim was to assess the clinical, laboratory and radiological features of SAPHO syndrome. Methods We recruited all patients presenting to Peking Union Medical College Hospital from 2004 to 2015 diagnosed with SAPHO syndrome. The medical data, laboratory test results and imaging were collected for all patients. Results One hundred and sixty-four patients (111 women and 53 men) were recruited to our cohort. The mean age of the patients was 40.71 years. Nine patients had osteoarticular symptoms without skin involvement. One hundred and forty-three and 25 patients had palmoplantar pustulosis and severe acne, respectively. Psoriasis vulgaris was accompanied by palmoplantar pustulosis or severe acne in 24 patients. One hundred and sixty-four patients suffered from pain in the anterior chest wall, followed by spine (12 in the cervical region, 36 in the thoracic region and 111 in the lumbosacral region) and peripheral joint (136 patients) involvement. None of the patients had IBD. The hs-CRP level was increased in 70.8% patients. Only 2.4% were HLA-B27 positive. CT scan indicated osteolysis, sclerosis and hyperostosis in the anterior chest wall and spine in SAPHO syndrome patients. The bull-horn sign was the typical characteristic of SAPHO syndrome seen in bone scintigraphy images. One hundred and thirty-one (79.9%), 85 (51.8%), 100 (61%) and 54 (32.9%) patients took NSAIDs, CSs, DMARDs and oral bisphosphonates, respectively. Conclusion SAPHO syndrome is predominant in middle-age women, characterized by dermatological and osteoarticular manifestations with unknown aetiology. CT scan and bone scintigraphy are useful for diagnosis. There is still no standard treatment to control the disease.

An unsupervised feature learning framework based on auto-encoder is proposed to learn sparse feature representations for remote-sensing imagery retrieval in this letter. The low-level feature descriptors are extracted and exploited to learn a set of feature extractors, which are then used to encode the low-level feature descriptors to generate new sparse features. The learned feature representations are applied to aerial images randomly selected from the University of California Merced data set. The results indicate that the performance of our proposed framework is comparable or superior to that of the state-of-the-art method. The framework is proved to be an effective approach to manage the huge volume of remote-sensing data and to retrieve the desired remote-sensing imagery.

Purpose – The purpose of this paper is to improve the retrieval results of hyperspectral image by integrating both spectral and textural features. For this purpose, an improved multiscale opponent representation for hyperspectral texture is proposed to represent the spatial information of the hyperspectral scene. Design/methodology/approach – In the presented approach, end-member signatures are extracted as spectral features by means of the widely used end-member induction algorithm N-FINDR, and the improved multiscale opponent representation is extracted from the first three principal components of the hyperspectral data based on Gabor filters. Then, the combination similarity between query image and other images in the database is calculated, and the first k more similar images are returned in descending order of the combination similarity. Findings – Some experiments are calculated using the airborne hyperspectral data of Washington DC Mall. According to the experimental results, the proposed method improves the retrieval results, especially for image categories that have regular textural structures. Originality/value – The paper presents an effective retrieval method for hyperspectral images.

Objective This study aimed to summarize the diagnosis, therapy, and prognosis of pituitary metastasis. Methods Ten patients from the Department of Neurosurgery of the Peking Union Medical College Hospital from April 1997 to August 2014 were retrospectively analyzed. Results The participants included 7 males (70%) and 3 females (30%), with an average age of 60.4 years. The most common initial clinical feature was visual disability (50%). The postoperative pathology reports indicated 1 case (10%) of metastatic large-cell pulmonary carcinoma, 2 cases (20%) of metastatic small cell pulmonary carcinoma, 2 cases (20%) of clear cell renal carcinoma metastasis, and 5 cases (50%) of metastasis of adenocarcinomas from different areas. All the patients underwent a thorough follow-up, and the average survival was 144 days. Conclusions Pituitary metastasis is a rare disease. Its diagnosis depends on the clinical manifestations and radiologic results. The primary therapeutic method is surgery and subsequent radiotherapy and chemotherapy; however, the prognosis of this disease is poor.

Mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) are two well recognized entities of precursor cystic lesions of pancreatic duct adenocarcinoma. The characteristic features of MCNs are the lined mucinous epithelium with underlying ovarian-type stroma, but without communication with the ducts, while that for IPMNs are the communication with the ducts but without the underlying ovarian-type stroma. Here we report a case of MCN communicating with the main pancreatic duct in a 68-year-old woman. The initial radiographic diagnosis was pancreatic IPMN with main pancreatic involvement and this was also confirmed during gross examination. Histologically, the pancreatic cystic neoplasm was lined with mucinous epithelium with underlying ovarian-type of stroma. Immunohistochemical stains confirmed that the stroma cells were positive for ER, PR, alpha-inhibin and focally positive for CD10. The final pathologic diagnosis was pancreatic mucinous cystic neoplasm communicating with the main pancreatic duct. To the best of our knowledge, this is the second pathology confirmed case of MCN communicating with the main pancreatic duct. A careful gross examination and bivalvation of the main duct communicating with the cystic neoplasm helps render the correct diagnosis. If more cases are reported in the future, the MCN communicating with duct could become a new entity of pancreatic mucinous neoplasm.

Aims: Cigarette smoking (CS) triggers airway inflammation by activating immune responses. IRAK-M, expressed by airway epithelial cells and macrophages, negatively regulates Toll-like receptor-mediated NFkB activation. IRAK-M has dual properties in the various disease contexts. We studied the effect of IRAK-M on airway inflammation induced by CS under short-term CS exposure followed by LPS insult and 7-week CS challenge using IRAK-M knockout (IRAK-M -/-) mice using a number of cellular and molecular techniques. Results: After LPS insult following short-term CS exposure, compared with wild-type mice, IRAK-M-/- mice demonstrated worsened airway inflammation, significantly higher percentage of Th17 cells in lungs and concentrations of inflammatory cytokines in lungs (figure 1), and significantly elevated expression of costimulatory molecules CD40 and CD86 by lung dendritic cells (DCs) or macrophages. Conversely, after 7-week CS exposure, IRAK-M-/- demonstrated significantly attenuated airway inflammation and lower, significantly lower concentrations of cytokines in lungs homogenates, significantly increased percentage of Tregs (figure 2), and lower expression of CD11b and CD86 by lung DCs or macrophages compared to WT mice. Conclusions: IRAK-M signaling plays protection or damage in airway inflammation induced by CS depending on the duration of CS in a mouse. A better understanding of IRAK-M’s effect on airway inflammation induced CS during the various phases of insult might be helpful in modulating CS-associated airway pathology.

Vitamin D3 is beneficial in ameliorating or preventing inflammation and carcinogenesis. Here, we evaluated if vitamin D3 has a preventive effect on colitis-associated carcinogenesis. Administration of azoxymethane (AOM), followed with dextran sulfate sodium (DSS), was used to simulate colitis-associated colon cancer in mice. The supplement of vitamin D3 at different dosages (15, 30, 60 IU·g·w), started before AOM or immediately after DSS treatment (post 60), was sustained to the end of the experiment. Dietary vitamin D3 significantly reduced the number of tumors and tumor burden in a dose-dependent manner. Of note, vitamin D3 in high doses showed significant preventive effects on carcinogenesis regardless of administration before or after AOM-DSS treatment. Cell proliferation decreased in vitamin D3 groups compared with the control group after inhibition of expression of β-catenin and its downstream target gene cyclin D1 in the colon. In vitro, vitamin D3 reduced the transcriptional activity and nuclear level of β-catenin, and it also increased E-cadherin expression and its binding affinity for β-catenin. Moreover, repression of E-cadherin was rescued by supplemental vitamin D3 in mouse colons. Taken together, our results indicate that vitamin D3 effectively suppressed colonic carcinogenesis in the AOM-DSS mouse model. Our findings further suggest that upregulation of E-cadherin contributes to the preventive effect of vitamin D3 on β-catenin activity.

Background. IRAK-M, negatively regulating Toll-like receptor, is shown the dual properties in the varied disease contexts. We studied the effect of IRAK-M deficiency on cigarette smoking- (CS-) induced airway inflammation under acute or subacute conditions in a mouse model.Methods. A number of cellular and molecular techniques were used to detect the differences between IRAK-M knockout (KO) and wild type (WT) mice exposed to 3-day or 7-week CS.Results. Airway inflammation was comparable between IRAK-M KO and WT mice under 3-day CS exposure. Upon short-term CS exposure and lipopolysaccharide (LPS) inhalation, IRAK-M KO mice demonstrated worse airway inflammation, significantly higher percentage of Th17 cells and concentrations of proinflammatory cytokines in the lungs, and significantly elevated expression of costimulatory molecules CD40 and CD86 by lung dendritic cells (DCs) or macrophages. Conversely, 7-week CS exposed IRAK-M KO mice demonstrated significantly attenuated airway inflammation, significantly lower concentrations of proinflammatory cytokines in the lungs, significantly increased percentage of Tregs, and lower expression of CD11b and CD86 by lung DCs or macrophages.Conclusions. IRAK-M plays distinctive effect on CS-induced airway inflammation, and influences Treg/Th17 balance and expression of costimulatory molecules by DCs and macrophages, depending on duration and intensity of stimulus.

BACKGROUND Cytomegalovirus (CMV) infection has been shown to be related to severe or steroid-refractory ulcerative colitis (UC) flare-ups. The aim of this study was to evaluate the endoscopic and pathological characteristics of CMV colitis in patients with UC and to assess the predictive value of the endoscopic and pathological features of CMV colitis. METHODS A total of 50 consecutive UC patients with CMV infection who were admitted to Peking Union Medical College Hospital from 2010 to 2015 were enrolled in this study. RESULTS Twenty-five UC patients with CMV infection (50.0%) had concurrent CMV colitis. When the cutoff value was set at 1150 copies, the sensitivity and specificity of blood CMV DNAq polymerase chain reaction for predicting CMV colitis were 44.4% and 78.9%, respectively. A higher proportion of endoscopic punched-out ulcers, irregular ulcers, and cobblestone-like appearance were observed among the patients in the CMV colitis group than those in the non-CMV colitis group (52.0% versus 20.0%, 60.0% versus 16.0%, and 20.0% versus 0%, respectively, P < 0.05). The number of CMV inclusion bodies per high-power field was significantly higher in those with punch-out ulcerations (25.7% versus 60.0%, P < 0.05). A higher grade of pathological inflammation was observed in the CMV colitis group than in the control group (68.0% versus 44.0%). CONCLUSIONS Characteristic endoscopic features with punch-out ulcers and high CMV viremia load may be useful for predicting the presence of CMV colitis in histology. Punch-out ulcers were found to be associated with a higher number of inclusion bodies on histology, suggesting a role of targeted biopsy for endoscopist.

Background Endometriosis is a relatively common condition in women of reproductive age. Malignant transformation of intestinal endometriosis is a very rare event. We report a case in which a patient with a history of endometriosis underwent surgery for malignant intestinal endometriosis. Case presentation A 55-year-old woman complained of rectorrhagia and intermittent abdominal pain. A neoplasm was revealed by colonoscopy, CT scan and F18-FDG PET/CT of the recto-sigmoidal colon. The patient underwent a rectal anterior resection, hysterectomy and bilateral salpingo-oophorectomy for treatment. According to the histological and immunohistochemical presentation, the diagnosis of endometriosis-associated recto-sigmoid cancer was confirmed. The patient was treated with adjuvant chemotherapy for 6 months. During the follow-up appointment 22 months later, there was clinical and radiographic evidence of recurrence in the rectum. The patient received chemotherapy again and will receive another surgery after two more cycles of chemotherapy. Conclusion We report a case of malignant intestinal endometriosis. Although there is no standard therapy for malignant intestinal endometriosis due to the rarity of this disease, surgery and adjuvant chemotherapy seemed to be rational. This case indicates that local recurrence may be a common situation after standard therapy.

Cytomegalovirus (CMV) gastritis is a rare opportunistic infection with diverse clinical manifestations. Our study aimed to investigate the clinical features of Chinese patients with CMV gastritis. Six inpatients diagnosed with CMV gastritis were retrospectively enrolled, based on the finding of inclusion bodies in routine hematoxylin and eosin staining or positive anti-CMV monoclonal antibodies under immunohistochemistry in the gastric biopsy. Data, including demographics, diagnostic measurements, and medications, were collected. Abdominal pain was the most frequently reported symptom, occurring in 4 patients. Five patients were immunocompromised with associated underlying diseases, and 3 patients had decreased leukocyte differentiation antigen 4 positive (CD4+) T lymphocyte counts. Only 3 patients had either positive cytomegalovirus (CMV)-immunoglobulin (Ig) M or increased copies of CMV-DNA peripherally. All patients had gastric lesions in the antrum of the stomach, including ulcers or erosions observed by gastroscopy. All patients received ganciclovir by intravenous injection (IV) as the first line anti-CMV therapy, and attained complete (4) or partial remission (2) during the follow-up. CMV gastritis should be taken into consideration in patients with immunocompromised status who have abdominal pain, nausea, or vomiting. Gastroscopy and necessary biopsy are the major diagnostic methods for CMV gastritis. Early diagnosis leads to a better prognosis for these patients.

Low-level features tend to achieve unsatisfactory retrieval results in remote sensing image retrieval community because of the existence of semantic gap. In order to improve retrieval precision, visual attention model is used to extract salient objects from image according to their saliency. Then color and texture features are extracted from salient objects and regarded as feature vectors for image retrieval. Experimental results demonstrate that our method improves retrieval results and obtains higher precision.

Long-standing inflammatory bowel disease is associated with increased risk of developing colorectal adenocarcinoma. Significant intra- and inter-observers' variability exists in histologic interpretation of dysplasia in surveillance biopsies. In this study, we evaluated the utility of a panel of immunohistochemical markers in diagnosing inflammatory bowel disease-associated neoplasia. We reviewed 39 colectomy specimens with inflammatory bowel disease-associated neoplasia. In these 39 cases, we identified 172 foci of interest (5 normal, 58 negative for dysplasia, 15 indefinite for dysplasia, 59 low-grade dysplasia, 18 high-grade dysplasia, and 17 invasive adenocarcinoma). They were subjected to immunohistochemistry for TP53 and CK7. Logistic regression was used to evaluate their association with the presence of dysplasia. Receiver operating characteristic curves were used to determine the optimal cutoffs and assess the diagnostic performance of TP53 and CK7. Both TP53 nuclear staining and CK7 immunoreactivity gradually increased in the progression of inflammatory bowel disease-associated neoplasia (P0.0001). CK7 immunoreactivity increased along with the increase of inflammation severity (P=0.0002) as well as reactive changes (P=0.04) in the colonic mucosa. But TP53 nuclear staining was independent of either feature. When both TP538% and CK730% as identified from logistic regression and receiver operating characteristic curves were used to diagnose dysplasia, the specificity achieved as high as 95%. When either TP538% or CK730% was used to diagnose dysplasia, the sensitivity achieved was 82%. Our results suggested that a combination of CK7 and TP53 immunohistochemistry may be helpful in diagnosing inflammatory bowel disease-associated dysplasia in difficult cases.

Gastric intestinal metaplasia can display cytoarchitectural atypia that falls short of qualifying for dysplasia but can be classified as indefinite for dysplasia. Yet few studies have evaluated the prevalence, the morphologic, and biologic characteristics of this variant. Out of a cohort of 554 biopsies with chronic atrophic gastritis and/or dysplasia, we categorized the cases as either (1) simple intestinal metaplasia; (2) intestinal metaplasia with hyperplasia; (3) intestinal metaplasia with basal gland atypia; and (4) gastric dysplasia. The relationship between the subtypes and various clinicopathologic features, mucin immunophenotypes, and biologic characteristics was evaluated. The final cohort consisted of 424 cases of simple intestinal metaplasia, 93 intestinal metaplasia with hyperplasia, 16 intestinal metaplasia with basal gland atypia, and 21 gastric dysplasia. Intestinal metaplasia with basal gland atypia had a prevalence of 2.8% and similar to gastric dysplasia, 3.7%. Both of these lesions were similar in body/fundus distribution (12.5%) and paucity of goblet cells (68.8%). Intestinal metaplasia with basal gland atypia and gastric dysplasia seem to share some biologic similarities but with a lower frequency of alpha-methylacyl-CoA racemase expression (25% versus 62%), p53 expression (6.3% versus 47.6%), and increased Ki-67 index on surface/pit and isthmus in intestinal metaplasia with basal gland atypia. Alternatively, simple intestinal metaplasia and intestinal metaplasia with hyperplasia did not differ statistically with regard to the various characteristics evaluated. We concluded that gastric intestinal metaplasia can be divided into 2 broad categories that are readily defined by cytoarchitectural and biologic characteristics. Based on the characteristics of intestinal metaplasia with basal gland atypia and in keeping with others, we confirm that this subtype could represent a preneoplastic lesion that needs further evaluation.

Background Conventional biliary brush via ERCP has low clinical detection for biliary malignancy. Therefore, new approaches are needed to facilitate diagnosis. We therefore explored the application of fluorescent in situ hybrization (FISH) using a UroVysion kit for the detection of malignancy in the bile duct. Methods Genetic alterations of target chromosomes such as aneuploidy in Chinese biliary cancer cell lines and tissues were measured using a UroVysion kit. The diagnostic value of the FISH assay was assessed by probing 27 brush samples of biliary cytology and control routine cytology (RC) samples. The gold standard was established by the pathology or clinical outcomes at the 12-month follow-up. Results Aneuploidy is commonly found in cell lines and tissues of biliary cancers, but not in normal cells or tissues. Here we probed for aneuploidy in clinical biliary brush specimens obtained by ERCP using FISH and a UroVysion kit. The sensitivity, specificity, and positive and negative predictive values for biliary malignancy were found to be 50%, 100%, 100% and 31.3%, respectively. The sensitivity, specificity, and positive and negative predictive values by RC were found to be 22.7%, 100%, 100% and 22.7%, respectively. In combination with RC, FISH increased the diagnostic sensitivity to 63.6% although this difference was not found to be statistically significant. Conclusions Aneuploidy is frequently present in bile duct carcinomas. Here we found that the FISH assay is useful for the detection of Chinese biliary cancers.

Background The extent of lymphadenectomy during laparoscopic right colectomy can affect the oncological outcome and the safety of surgery. The principle of complete mesocolic excision (CME) has been gradually accepted and increasingly applied by colorectal surgeons. The aim of this study is to investigate whether extended lymphadenectomy (CME) in laparoscopic colectomy could improve the oncological outcomes of patients with right-sided colon cancers, compared with D2 lymphadenectomy. Methods/design The Radical Extent of lympadenectomy: D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) study is a prospective, multicenter, randomized controlled trial in which 1072 eligible patients with right-sided colon cancers will be randomly assigned to the CME group or the D2 dissection group during laparoscopic right colectomy. Inclusion criteria are locally advanced colon cancers situated from the cecum to the right third of the transverse colon and clinically staged as T2-4aN0M0 or TanyN + M0. The primary endpoint of this trial is 3-year disease-free survival. Secondary endpoints include 3-year overall survival, postoperative complication rates, perioperative mortality rates, and rates of positive central lymph nodes (the station 3 nodes). Discussion The RELARC trial is a prospective, multicenter, randomized controlled trial that will provide evidence on the optimal extent of lymphadenectomy during laparoscopic right colectomy in terms of better oncological outcome and operation safety. Trial registration ClinicalTrials.gov: NCT02619942. Registered on 29 November 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1710-9) contains supplementary material, which is available to authorized users.

Aim Locally advanced rectal cancer (LARC) is frequently treated with neoadjuvant chemoradiotherapy (NACRT) to reduce the risk of local recurrence and improve survival. Tumour response to NACRT is variable and may influence the prognosis after subsequent surgery. This study compared the prognostic values of tumour regression grade (TRG) and neoadjuvant pathologic (ypTNM) downstaging in stage II and III rectal cancer patients treated with NACRT followed by curative surgery. Method This study included 185 LARC patients treated with long-course radiotherapy (45 Gy in 25 fractions) plus 5-fluorouracil over 5 weeks between 2005 and 2013. We used multivariate analysis to assess the relationship of Dworak's five-tier tumour regression grade (TRG), ypTNM stage, and ypTNM downstaging with clinicopathologic factors, 5-year disease free survival (DFS), and 5-year overall survival (OS). Results Total regression (TRG4), good regression (TRG3), moderate regression (TRG2), minor regression (TRG1), and no regression (TRG0) were seen in 38 (20.6%), 65 (35.2%), 43 (23.2%), 28 (15.1%), and 11 (5.9%) patients, respectively. TNM downstaging following NACRT occurred in 109 (58.9%) patients. The 5-year DFS rates after NACRT for TRG0, TRG1, TRG2, TRG3, and TRG4 were 0%, 58.5%, 66.4%, 80.4%, and 82.6%, respectively (P < 0.001). The ypTNM stage correlated with 5-year DFS (P = 0.004) but not 5-year OS (P = 0.075). Multivariate analysis demonstrated that TRG related to both DFS and OS (P < 0.001). Conclusion TRG measured on a five-tier system was better than ypTNM stage for predicting outcome in LARC patients treated with NACRT and surgery. This article is protected by copyright. All rights reserved.

Learning powerful feature representations is of great importance in order to improve the accuracy of high-resolution remote sensing imagery (HRRSI) scene classification. Generally, traditional methods mainly focus on low-level features. Though these feature representations can achieve satisfactory performance to some extent, the performance improvement is small. More importantly, these low-level feature representations are hand-crafted features, and it is difficult to design such a holistic feature representation. Recently, convolutional neural networks (CNN) has achieved remarkable performance on several natural benchmarks. In this paper, we investigate the extraction of the deep feature representations based on the pre-trained CNN architectures for scene classification tasks. More specially, we first evaluate the pre-trained CNN architectures on a public scene dataset and then fine-tune the CNN that performs best on the dataset using the target HRRSI dataset to learn dataset-specific features. Extensive experiments on two publicly available scene datasets indicate that the deep feature representations can achieve state-of-the-art performance.

Rationale Primary lymphoma that arises from the intestine is an uncommon malignant tumour, while intestinal fistula caused by primary lymphoma is even rarer. Non-specific clinical performance makes early diagnosis difficult, although imaging modalities might play an essential role in the detection of intestinal fistula. Patient concerns Patient 1: A 60-year-old male hospitalized with diarrhoea and abdominal pain for seven months underwent computed tomography enterography (CTE) that demonstrated ileum internal fistula and ileac-sigmoid colon fistula. Ultrasound (US) showed small intestinal wall thickened and development of a fistula of the sigmoid colon due to malignance. Patient 2: A 43-year-old male presented with abdominal pain and diarrhoea lasting one year. US revealed a fistula between the sigmoid colon and the ileum, and CTE showed that the wall of the partial sigmoid colon was abnormally thickened and enhanced with an ileal-sigmoid fistula that strongly suggested the diagnosis of lymphoma. Diagnoses Both the two patients were diagnosed as intestinal fistula caused by primary non-Hodgkin's intestinal lymphoma. Interventions The patient 1 underwent surgery followed by chemotherapy. The patient 2 accepted chemotherapy. Outcomes Two patients' general conditions remained stable and the imaging revealed no recurrence after follow-up of about 12 months. Lessions Cross-sectional imaging, such as US and CT, plays an essential role in intestinal lymphoma fistula diagnosis.

Aim: CXCR3, via binding its specific ligand CXCL10, plays an important role in cigarette smoke (CS)-induced pulmonary inflammation. CXCR3 is preferentially expressed in activated T cells (chiefly CD8 + T cells). The purpose of this study was to investigate the role of CXCR3 in CS-induced pulmonary injury using CXCR3 gene-deficient (CXCR3 −/− ) mice. Methods: Differences in the infiltration of inflammatory cells and CD8 + T cells and the expression of inflammatory mediators and chemokines in the bronchoalveolar lavage fluid and lungs at the mRNA and protein levels were compared between CXCR3 −/− mice and wild-type (WT) mice at 2 h after 3 d of CS exposure. Results: Compared with their WT counterparts, the CXCR3 −/− mice showed alleviated inflammation, as evidenced by fewer inflammatory cells, particularly cytotoxic CD8+ T cells, in bronchoalveolar lavage fluid and lung tissues. At both the mRNA and protein levels, there were significantly lower levels of inflammatory and chemotactic cytokines, including TNF-α, interleukin-8, interferon-γ, transforming growth factor-β1, and CXCL10 in the CXCR3 −/− mice. Conclusion: Our data show that CXCR3 is important in recruiting inflammatory cells (particularly CD8 + T cells) into the airways and lungs, as well as initiating inflammatory and fibrotic cytokines release at 2 h following a short-term CS insult. CXCR3 could be a novel target for the treatment of pulmonary inflammation induced by CS.

To discuss the diverse imaging features of pancreatic and extra-pancreatic lesions of IgG4-related disease (IgG4-RD) on multi-detector CT (MDCT). This retrospective study was approved by our institutional research ethics board, and informed consent was waived. From 2008 to 2013, 159 patients including 120 men (mean age 57 years; range 27–79 years) and 39 women (mean age 51 years; range 25–83 years) who met the comprehensive diagnostic criteria for IgG4-RD (2011) were enrolled. MDCT images consisted of 153 abdominal images, 64 pelvic images, 64 thoracic images, and 8 neck images were retrospectively analyzed in consensus by two radiologists with expertise in the CT diagnosis of IgG4-RD. Only 11 (11/153, 7.2%) IgG4-RD patients had been found with no pancreatic involvement. 145 (145/159, 91.2%) patients had various extra-pancreatic lesions, including involvement of biliary tree (93/153, 60.8%), peri-pancreatic vessels (66/153, 43.1%), IgG4-related lymphadenopathy, peri-abdominal aorta arteritis or retroperitoneal fibrosis, head and neck lesions, etc. Renal lesions were found in 26 (26/153, 17.0%) IgG4-RD patients with 4 types of renal parenchymal involvement. Lung lesions were found in 44 (44/64, 68.7%) IgG4-RD patients, which were classified into 7 types. Pancreatic and various extra-pancreatic lesions may be involved in IgG4-RD patients frequently with typical imaging findings. It is useful to recognize the atypical or uncommon imaging features to help the diagnosis of IgG4-RD together with other serologic or histopathologic findings.

Rationale: The lower rectal gastrointestinal stromal tumor (GIST) is a rare entity and warrants special attentions because of the considerations of preserving of anal and urinal functions. Neoadjuvant therapy with imatinib mesylate (IM) has achieved great success in GIST, which potentially extends the applications of function-preserving minimally invasive surgical procedures. Transanal endoscopic microsurgery (TEM) is a well-developed minimally invasive technique for benign tumors in lower rectum. Herein, we reported the initial application of TEM for high risk GIST after IM treatment. Patient concerns: A 52-year-old woman suffered mild lower abdominal pain and perianal discomfort. Physical examination found a soft mass 4 cm far away from anal verge. Rectal MRI and transrectal ultrasound (TRUS) showed that there was a 1.9 × 1.6 cm submucosal mass in the lower rectum. The incisional biopsy was performed and the pathological result reported it was a high-risk GIST. Diagnoses: High-risk lower rectal GIST. Interventions: IM was given for neoadjuvant therapy. Then TEM was adopted to resect the residual tumor. IM was restored 4 weeks after surgery. Outcomes: The final pathological results reported the margin was clear. After an 18-month follow up, no recurrence and metastasis was found and the patient had a satisfactory anal and urinal functions. Lessons: TEM in combination with IM could be a practical strategy for the high-risk lower rectal GIST simultaneously to achieve curative resection and to preserve the anal and urinal functions that can significantly improve the life quality of the patients.

Interleukin-22 (IL-22) exhibits both proinflammatory and anti-inflammatory properties in various biological processes. In this study we explored the effects of exogenous recombinant IL-22 (rIL-22) on cigarette smoke (CS)-induced airway inflammation in mice.Male C57BL/6 mice were divided into groups: (1) CS group exposed to tobacco smoke for 3 consecutive days, (2) rIL-22 group received rIL-22 (100 mg/kg, ip), and (3) CS plus rIL-22 group, received rIL-22 (100 mg/kg, ip) before the CS exposure. The airway resistance (Rn), lung morphology, inflammatory cells in the airways, and inflammatory cytokines and CXCR3 ligands in both bronchoalveolar lavage (BAL) fluids and lung tissues were analyzed.CS alone significantly elevated IL-22 level in the BAL fluid. Both CS and rIL-22 significantly augmented airway resistance, an influx of inflammatory cells into the airways and lung parenchyma, and significantly elevated levels of pro-inflammatory cytokines (TGFβ1 and IL-17A) and CXCR3 chemokines (particularly CXCL10) at the mRNA and/or protein levels. Furthermore, the effects of rIL-22 on airway resistance and inflammation were synergistic with those of CS, as demonstrated by a further increased Rn value, infiltration of greater numbers of inflammatory cells into the lung, higher levels of inflammatory cytokines and chemokines, and more severe pathological changes in CS plus rIL-22 group as compared to those in CS group.Exogenous rIL-22 exacerbates the airway inflammatory responses to CS exposure in part by inducing expression of several proinflammatory cytokines and CXCR3 ligands.

To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma.Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology (GO) enrichment analysis was performed using the GeneSpring software GX 12.6. The differentially expressed gene was verified using a real-time TaqMan® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G0S2 were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens.The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor κB (NF-κB) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G0/G1 switch 2 (G0S2) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-κB cascade, and its expression was validated in independent samples through real-time TaqMan® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN (P0.01 and P0.001, respectively). In IHC analysis, G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G0S2 expression in HGIN was higher than that of LGIN (P = 0.012, χ (2) = 6.28) and EGC (P = 0.008, χ (2) = 6.94).A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application.

To retrospectively explore the value of apparent diffusion coefficient (ADC) histogram in assessing local aggressiveness of cervical cancer.53 patients with cervical cancer, including 7 cases at stage IB1, 17 cases at stage IB2 and 29 cases at stage IIA, were subjected to preoperative MRI including diffusion-weighted imaging with b values of 0 and 800 s/mm(2). The average of mean ADC values (ADCmean), minimum ADC values (ADCmin) and the 5th to 85th percentile ADC values every 10 % (ADC5 %, ADC15 %, ADC85 %) were measured. ADC values were compared between subgroups according to pathologic subtype, histological differentiation, depth of cervical infiltration, and lymph node metastases.ADCmean and ADCmin for adenocarcinoma were 1,170.3 ± 97.8 × 10(-6) and 748.7 ± 157.5 × 10(-6) mm(2) s(-1), respectively, significantly higher than that of squamous cell carcinoma (SCC) (1,053.8 ± 134.3 × 10(-6) and 615.6 ± 170.2 × 10(-6) mm(2) s(-1), respectively). ADCmean and ADC5 %-ADC85 % of well or moderately tumor were significantly higher than poorly differentiated tumor, but ADCmin was not significantly different among different differentiated cervical cancer. Only ADC5 %-ADC45 % could discriminate well or moderately differentiated SCC from poorly differentiated SCC. ADC5 % for distinguishing well/moderately from poorly differentiated cervical cancer had a largest AUC (0.83). There was no statistical difference in ADC value for different depth of cervical infiltration or lymph node metastases.ADC values are helpful in assessing pathologic subtype and the differentiation of cervical cancer.

Nodular regenerative hyperplasia (NRH) of liver may be one of the leading causes of non-cirrhotic intrahepatic portal hypertension (NCIPH), although the exact relationship is currently unknown. Diagnosis of NRH is relatively difficult and involves surgical pathology, and thus it is necessary to improve the preoperative recognition of NRH. Here, we analyze 15 cases of NRH to better understand this disease. All the liver specimens were microscopically examined by hematoxylin-eosin staining and reticulin and Masson trichrome staining. Diagnoses of NRH were confirmed by pathological examination. Clinically, NRH presents as diffused liver lesions with mildly increased liver enzymes. Portal hypertension is the most common clinical manifestation presenting prominently as splenomegaly, hypersplenism, and esophageal varices bleeding. NRH is often associated with autoimmune or collagen vascular diseases, and such patients often present with a variety of positive autoantibodies and increased erythrocyte sedimentation rate (ESR), Ig and γ %. Pathological examination of the liver showed diffuse small regenerative nodules without fibrous septa and obstructive portal venopathy. For those patients with portal hypertension of unknown cause and preserved liver function, especially, those combined with autoimmune diseases, NRH should be considered.

Background Metabolites of arachidonic acid such as prostacyclin (PGI2) have been shown to participate in the pathogenesis of pulmonary fibrosis by inhibiting the expression of pro-inflammatory and pro-fibrotic mediators. In this investigation, we examined whether iloprost, a stable PGI2 analogue, could prevent bleomycin-induced pulmonary inflammation and fibrosis in a mouse model. Methods Mice received a single intratracheal injection of bleomycin with or without intraperitoneal iloprost. Pulmonary inflammation and fibrosis were analysed by histological evaluation, cellular composition of bronchoalveolar lavage (BAL) fluid, and hydroxyproline content. Lung mechanics were measured. We also analysed the expression of inflammatory mediators in BAL fluid and lung tissue. Results Administration of iloprost significantly improved survival rate and reduced weight loss in the mice induced by bleomycin. The severe inflammatory response and fibrotic changes were significantly attenuated in the mice treated with iloprost as shown by reduction in infiltration of inflammatory cells into the airways and pulmonary parenchyma, diminution in interstitial collagen deposition, and lung hydroxyproline content. Iloprost significantly improved lung static compliance and tissue elastance. It increased the expression of IFNγ and CXCL10 in lung tissue measured by RT-PCR and their levels in BAL fluid as measured by ELISA. Levels of TNFα, IL-6 and TGFβ1 were lowered by iloprost. Conclusions Iloprost prevents bleomycin-induced pulmonary fibrosis, possibly by upregulating antifibrotic mediators (IFNγ and CXCL10) and downregulating pro-inflammatory and pro-fibrotic cytokines (TNFα, IL-6, and TGFβ1). Prostacyclin may represent a novel pharmacological agent for treating pulmonary fibrotic diseases.

Background Repeated qualitative fecal immunochemical test (qlFIT) is a clinical strategy widely used to detect lower gastrointestinal lesions, but its diagnostic power has not been assessed in opportunistic screening for colorectal neoplasia. Objective This study aimed to determine the performance of three-sample qlFIT in screening for colorectal cancer and its precursors in high-risk participants. Methods 513 gastrointestinal outpatients yielded three qlFITs before a standard colonoscopy. We evaluated the diagnostic value of one, two, and three positive qlFITs serving as the positivity threshold. The risk factors of colorectal neoplasia to yield positive qlFITs were also determined. Results 52 patients were diagnosed with colorectal cancer and 70 with advanced adenomatous polyp. For colorectal cancer, the sensitivity and specificity of one positive qlFIT were 90.4% and 53.8%, of two were 80.8% and 75.1%, and of three were 53.9% and 88.5%, respectively. For advanced adenomatous polyp, the sensitivity and specificity of one positive qlFIT were 81.4% and 54.2%, of two were 50.0% and 72.5%, and of three were 28.6% and 86.2%. Left-sided location (OR 2.50, 95%CI 1.26–4.95) and advanced histology of tumors (OR 3.08, 95%CI 1.58–6.01) were independently associated with positive qlFITs. Conclusions Three-sample qlFIT is a reasonably good method to detect colorectal neoplasia in high-risk population. Tumors in the left side or with advanced pathological features are more likely to produce positive qlFITs.

Texture features are widely used in image retrieval literature. However, conventional texture features are extracted from grayscale images without taking color information into con- sideration. We present two improved texture descriptors, named color Gabor wavelet texture (CGWT) and color Gabor opponent texture (CGOT), respectively, for the purpose of remote sensing image retrieval. The former consists of unichrome features computed from color chan- nels independently and opponent features computed across different color channels at different scales, while the latter consists of Gabor texture features and opponent features mentioned above. The two representations incorporate discriminative information among color bands, thus describing well the remote sensing images that have multiple objects. Experimental results demonstrate that CGWT yields better performance compared to other state-of-the-art texture features, and CGOT not only improves the retrieval results of some image classes that have unsatisfactory performance using CGWT representation, but also increases the average precision of all queried images further. In addition, a similarity measure function for proposed represen- tation CGOT has been defined to give a convincing evaluation. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. (DOI: 10.1117/1 .JRS.8.083584)

Background Chronic diarrhea in adults is a common symptom with a wide range of underlying etiologies. Although various strategies have been proposed for evaluation, there are still cases with undetermined origins even after extensive workup. Amyloidosis with gastrointestinal (GI) involvement is one of the causes that should be considered in adult patients with chronic diarrhea. We report a case of primary systemic amyloid light-chain (AL) amyloidosis, presenting initially as chronic diarrhea and weight loss. Case presentation A 43-year-old man with chronic diarrhea and weight loss was referred to our hospital. Prior to his presentation, extensive evaluation including an exploratory laparotomy was carried out and did not yield any valuable findings. An echocardiography performed after repeated episodes of orthostatic hypotension revealed infiltrative cardiomyopathy. Moreover, biopsies of the terminal ileum revealed amyloid deposition confirmed by Congo Red staining. Finally, a diagnosis of systemic AL amyloidosis was made after hematological workup. Anti-plasma cell therapy did ameliorate his GI symptoms. Conclusion Although amyloidosis with GI involvement is a rare cause of chronic diarrhea, it should be considered especially in patients with intestinal malabsorption and extra-GI manifestations, such as orthostatic hypotension. The delayed diagnosis in the present case highlights the importance of recognizing clinical “red flags” not seemingly related to one another, and underscores the need to get intestinal biopsies even with normal endoscopic appearance of the mucosa.