Differential diagnosis of adrenal adenomas and metastases using spectral parameters in dual-layer detector spectral CT.

OBJECTIVE: To assess the diagnostic value of spectral parameters in differentiating adrenal adenomas from metastases based on dual-layer detector spectral CT (DLSCT). MATERIALS AND METHODS: Patients with adenomas or metastases who underwent enhanced DLSCT of the adrenals were enrolled. The CT values of virtual non-contrast images (CTVNC), iodine density (ID) values, and Z-effective (Z-eff) values, the normalized iodine density (NID) values, slopes of spectral HU curves (s-SHC), and iodine-to-CTVNC ratios of the tumors were measured in each phase. Receiver operating characteristic (ROC) curves were used to compare the diagnostic values. RESULTS: Ninety-nine patients with 106 adrenal lesions (63 adenomas, 43 metastases) were included. In the venous phase, all spectral parameters were significantly different between adenomas and metastases (all p < 0.05). The combined spectral parameters showed a better diagnostic performance in the venous phase than in other phase (p < 0.05). The iodine-to-CTVNC value had a larger area under the ROC curve (AUC) than the other spectral parameters in the differential diagnosis of adenomas and metastases, with a diagnostic sensitivity and specificity of 74.4% and 91.9%, respectively. In the differential diagnosis of lipid-rich adenomas, lipid-poor adenomas and metastases, the CTVNC value and s-SHC value also had a larger AUC than the other spectral parameters, with a diagnostic sensitivity of 97.7%, 79.1% and specificity of 91.2%, 93.1%, respectively. CONCLUSION: On DLSCT, the combined spectral parameters in the venous phase could help better distinguish adrenal adenomas from metastases. The iodine-to-CTVNC, CTVNC and s-SHC values had the highest AUC values in differentiating adenomas, lipid-rich adenomas and lipid-poor adenomas from metastases, respectively.

The association between disruption of the circadian rhythm and aggravation of colitis in mice.

Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation. The circadian rhythm controls cell proliferation and energy metabolism. However, the role of circadian genes in inflammatory bowel disease is largely unknown. The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism. Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days, whereas those in the control group were not. Subsequently, half of the mice in the control and jet-lagged groups were given dextran sodium sulfate (DSS) to induce colitis. Mice in each group were euthanized at zeitgeber time (ZT)0, ZT4, ZT8, ZT12, ZT16, and ZT20. To investigate the effects of jet lag on the mice, colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2, and Nr1d1). We analysed the mitochondrial morphology, adenosine triphosphate (ATP) levels, and the expression of dynamin-related protein 1 (Drp1) and ser637-phosphorylated (p)-Drp1, which are closely related to ATP production. We further investigated the effect of PER2 knock-down in the colon epithelial cells (CCD 841 CoN) by measuring ATP and cell proliferation levels. Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice, altered the mitochondrial morphology of the colon specimens, decreased the expression of p-Drp1, reduced ATP production, and exacerbated inflammatory responses in mice with DSS-induced colitis. Additionally, silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation. Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis.

Impact of COVID-19 outbreak on the care of patients with inflammatory bowel disease: A comparison before and after the outbreak in South China.

BACKGROUND AND AIMS: Epidemics pose a great challenge to health care of patients. However, the impact of unprecedented situation of COVID-19 outbreak on health care of inflammatory bowel disease (IBD) patients in real-world setting has seldom been investigated. METHODS: We performed an observational study in a tertiary referral IBD center in China. The mode of health care and medication use was compared before and after COVID-19 outbreak. Electronic questionnaire surveys were performed among gastroenterologists and IBD patients to investigate the impact of COVID-19 outbreak on their attitudes towards telemedicine. RESULTS: COVID-19 outbreak resulted in substantial decrease of patients participating in standard face-to-face visit during 1 month post-outbreak (n = 51) than pre-outbreak (n = 249), whereas the participation in telemedicine was significantly higher than comparable period in 2019 (414 vs 93). During the 1 month after COVID-19 outbreak, 39 (39/56, 69.6%) patients had their infliximab infusion postponed with the mean delay of 3 weeks. The immunomodulator use was similar between pre-outbreak and post-outbreak. Six elective surgeries were postponed for a median of 43 days. In post-outbreak period, 193 (193/297, 64.98%) of the surveyed physicians have used telemedicine with an increase of 18.9% compared with 46.13% (137/292) in the pre-outbreak period (P < 0.001); 331 (331/505, 65.54%) of the surveyed IBD patients supported that the use of telemedicine should be increased in future health care. CONCLUSION: COVID-19 outbreak resulted in a great change in health-care access among IBD patients including decrease in standard face-to-face visit and delay of biologics use. There was an increased use and need of telemedicine after COVID-19 outbreak.

Impact of COVID-19 on the Healthcare of Patients With Inflammatory Bowel Disease: A Comparison Between Epicenter vs. Non-epicenter Areas.

Background and Aims: The COVID-19 pandemic poses a great challenge to healthcare. We aimed to investigate the impact of COVID-19 on the healthcare of patients with inflammatory bowel disease (IBD) in epicenter and non-epicenter areas. Methods: Patients with IBD from Hubei province (the epicenter of COVID-19) and Guangdong province (a non-epicenter area), China were surveyed during the pandemic. The questionnaire included change of medications (steroids, immunomodulators, and biologics), procedures (lab tests, endoscopy, and elective surgery), and healthcare mode (standard healthcare vs. telemedicine) during 1 month before and after the outbreak of COVID-19. Results: In total, 324 IBD patients from Guangdong province (non-epicenter) and 149 from Hubei province (epicenter) completed the questionnaire with comparable demographic characteristics. Compared to patients in Guangdong province (non-epicenter), significantly more patients in Hubei (epicenter) had delayed lab tests/endoscopy procedures [61.1% (91/149) vs. 25.3% (82/324), p < 0.001], drug withdrawal [28.6% (43/149) vs. 9.3% (30/324), p < 0.001], delayed biologics infusions [60.4% (90/149) vs. 19.1% (62/324), p < 0.001], and postponed elective surgery [16.1% (24/149) vs. 3.7% (12/324), p < 0.001]. There was an increased use of telemedicine after the outbreak compared to before the outbreak in Hubei province [38.9% (58/149) vs. 15.4% (23/149), p < 0.001], while such a significant increase was not observed in Guangdong province [21.9% (71/324) vs. 18.8% (61/324), p = 0.38]. Approximately two-thirds of IBD patients from both sites agreed that telemedicine should be increasingly used in future medical care. Conclusions: Our patient-based survey study in a real-world setting showed that COVID-19 resulted in a great impact on the healthcare of patients with IBD, and such an impact was more obvious in the epicenter compared to the non-epicenter area of COVID-19. Telemedicine offers a good solution to counteract the challenges in an unprecedented situation such as COVID-19.

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates. FINDINGS: We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2-5; range 0-15; I2=74%). The pooled prevalence of digestive symptoms was 15% (10-21; range: 2-57; I2=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9-32; range 1-53; I2=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of abdominal pain (odds ratio [OR] 7·10 [95% CI 1·93-26·07]; p=0·003; I2=0%) and abnormal liver function including increased ALT (1·89 [1·30-2·76]; p=0·0009; I2=10%) and increased AST (3·08 [2·14-4·42]; p<0·00001; I2=0%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4-19; range 3-23; I2=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22-5·48]; p=0·030; I2=73%). Patients with gastrointestinal involvement tended to have a poorer disease course (eg, acute respiratory distress syndrome OR 2·96 [95% CI 1·17-7·48]; p=0·02; I2=0%). INTERPRETATION: Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. FUNDING: None.

Role of non-inflammatory factors in intestinal fibrosis.

Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD), resulting in strictures and ultimately obstruction, which is a significant clinical problem. Fibrosis is mainly triggered by local chronic inflammation and occurs when excessive extracellular matrix deposition is caused by activated mesenchymal cells. Despite the advance of anti-inflammatory therapies in IBD, the incidence and preventive strategies of intestinal fibrosis and strictures in IBD have not significantly changed over time. This shows that inflammation is necessary for fibrosis, but it does not necessarily affect the fibrotic progression. This review summarizes current knowledge about the non-inflammatory mechanisms implicated in the gut fibrotic process of IBD, which may pave the way for new mechanisms and anti-fibrotic therapies.

Wet- versus dry-suction techniques for endoscopic ultrasound-guided fine-needle aspiration of solid lesions: a multicenter randomized controlled trial.

BACKGROUND: The optimal sampling techniques for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) remain unclear and have not been standardized. The aim of this study was to compare the wet-suction and dry-suction techniques for sampling solid lesions in the pancreas, mediastinum, and abdomen. METHODS: This was a multicenter, crossover, randomized controlled trial with randomized order of sampling techniques. The 296 consecutive patients underwent EUS-FNA with 22G needles and were randomized in a ratio of 1:1 into two separate groups that received the dry-suction and wet-suction techniques in a different order. The primary outcome was to compare the histological diagnostic accuracy of dry suction and wet suction for malignancy. The secondary outcomes were to compare the cytological diagnostic accuracy and specimen quality. RESULTS: Among the 269 patients with pancreatic (n = 161) and non-pancreatic (n = 108) lesions analyzed, the wet-suction technique had a significantly better histological diagnostic accuracy (84.9 % [95 % confidence interval (CI) 79.9 % - 89.0 %] vs. 73.2 % [95 %CI 67.1 % - 78.7 %]; P = 0.001), higher specimen adequacy (94.8 % vs. 78.8 %; P < 0.001), and less blood contamination (P < 0.001) than the dry-suction technique. In addition, sampling non-pancreatic lesions with two passes of wet suction provided a histological diagnostic accuracy of 91.6 %. CONCLUSIONS: The wet-suction technique in EUS-FNA generates better histological diagnostic accuracy and specimen quality than the dry-suction technique. Furthermore, sampling non-pancreatic lesions with two passes of EUS-FNA with wet suction may provide a definitive histological diagnosis when rapid on-site evaluation is not routinely available.

Risk factors for colorectal neoplasms based on colonoscopy and pathological diagnoses of Chinese citizens: a multicenter, case-control study.

PURPOSE: Since observational data in the urban residents are required to better assess the risk factors of colorectal neoplasm occurrence and the effectiveness of colonoscopy screening and surveillance, we conducted a case-control study at multicenters in China to identify patient characteristics and neoplasm features of colorectal adenoma (CRA) and colorectal carcinoma (CRC). METHODS: A total of 4089 patients who had undergone a colonoscopy from 19 hospitals were enrolled, of which 1106 had CRA and 466 had CRC. They were compared with controls. The analysis provides features and risk factors of colorectal neoplasm using multivariate logistic regression. RESULTS: Increasing age, a family history of colorectal cancer or previous cases of colorectal adenoma or hypertension disease, gastrointestinal surgery, regular intake of pickled food (adjusted odds ratio [aOR] 1.42, 95 % confidence interval [CI], 1.048-1.924), consumption of alcohol, and a positive result of fecal occult blood testing (FOBT; aOR 2.509, 95 % CI 1.485-4.237) were associated with an increased risk of CRA. In the CRC group, increasing age, regular intake of pickled foods, and a positive FOBT result were risk factors. In addition, a positive abdominal computed tomography (CT) before a colonoscopy and physical signs of emaciation were also significantly associated with an increasing risk of colorectal carcinoma. Regular intake of vegetables decreased the risk of both CRA and CRC. CONCLUSIONS: Age, pickled foods, and a positive FOBT are risk factors for colorectal neoplasm. Vegetable intake was associated with a decreased risk of CRA and CRC.

Selective expression of CYP2A13 in human pancreatic α-islet cells.

Exposure to cigarette smoke is an etiological factor of human pancreatic cancer and has been associated with an increased risk of pancreatic diseases, including pancreatitis and diabetes. The toxicants in cigarette smoke can reach pancreatic tissue, and most of the toxicants require cytochrome P450 (P450)-mediated metabolic activation to exert their toxicity. Among all the human P450 enzymes, CYP2A13 is the most efficient enzyme in the metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a major tobacco-specific toxicant and a suspected human carcinogen. It also metabolically activates 4-aminobiphenyl, another toxicant in cigarette smoke. Immunohistochemical analysis in this study demonstrated that CYP2A13 was selectively expressed in the islets but not in the exocrine portion of adult human pancreas. Further study using dual immunofluorescence labeling technique showed that CYP2A13 protein was mainly expressed in the α-islet but not in ß-islet cells. The selective expression of CYP2A13 in human pancreatic α-islet cells suggests that these islet cells could be damaged by the toxicants existing in cigarette smoke through CYP2A13-mediated in situ metabolic activation. Our result provides a mechanistic insight for human pancreatic diseases that have been associated with cigarette smoke exposure.

The characteristics of Barrett's esophagus: an analysis of 4120 cases in China.

Our objective was to investigate the endoscopic and clinico-pathological characteristics in patients with Barrett's esophagus (BE) in China. Using the terms 'Barrett's esophagus' and 'Barrett's esophagus, China' as key words, literatures published in Chinese and English journals were searched in Chinese data banks, as well as PubMed and ISI Web of Science from 1989 to 2007. An analysis was carried out with the standard inclusion and exclusion criteria. A total of 4120 cases were included in this study. BE was found in 2.44% of patients undergoing endoscopy for various symptoms of upper gastrointestinal tract diseases; the male : female ratio was 2.09 : 1, the average age of detection of BE was 53.15 years old, and 51% of patients with BE had typical symptoms for gastroesophageal reflux disease (GERD). The island-type BE was predominant (56.80%), and the occurrence of BE with special intestinal metaplasia (SIM) was 36.58%, but SIM was more common in tongue-type BE than island-type and circumferential-type BE (both P < 0.001), as well as in long segment BE (LSBE) than in short segment BE (SSBE) (P < 0.001). A total of 46.39% of patients had Helicobacter pylori infection. The mean length of follow up was 2 years in 492 patients. The incidence of adenocarcinoma was 0.61% patient-years of total follow up. In China, the endoscopic prevalence of BE is lower, but the average age of diagnosis is younger; a high proportion of H. pylori infection is found in patients with BE, and about half of the patients have no typical symptoms of GERD; the tongue-type BE and the LSBE are apt to SIM.

CYP2A13 in human respiratory tissues and lung cancers: an immunohistochemical study with a new peptide-specific antibody.

Human cytochrome P450 2A13 (CYP2A13) is highly efficient in the metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and another potent carcinogen, aflatoxin B1 (AFB1). Although previous studies demonstrated that CYP2A13 mRNA is predominantly expressed in human respiratory tissues, expression of CYP2A13 protein in these tissues and the involved cell types have not been determined because of the lack of CYP2A13-specific antibodies. To explore the toxicological and physiological function of CYP2A13, it is important to understand the tissue/cellular distribution of CYP2A13 protein. In this study, we generated a peptide-specific antibody against human CYP2A13 and demonstrated by immunoblot analysis that this antibody does not cross-react with heterologously expressed human CYP2A6 and mouse CYP2A5 proteins, both sharing a high degree of amino acid sequence similarity with CYP2A13. Nor does the antibody cross-react with heterologously expressed human CYP3A4, CYP2S1, or any of the cytochrome P450 enzymes present in the human liver microsomes. Using this highly specific antibody for immunohistochemical staining, we detected a high level of CYP2A13 protein expression in the epithelial cells of human bronchus and trachea, but a rare distribution in the alveolar cells. There was little expression of CYP2A13 protein in different types of lung cancers. In consideration of the high efficiency of CYP2A13 in NNK metabolic activation, our result is consistent with the reported observations that most smoking-related human lung cancers are bronchogenic and supports that CYP2A13-catalyzed in situ activation may play a critical role in human lung carcinogenesis related to NNK and AFB1 exposure.

[The clinical study of water loading in gastric sensation thresholds testing].

OBJECTIVE: To establish a simple, noninvasive, physiologic diagnostic assay for evaluating gastric sensation thresholds. METHODS: The gastric perception and discomfort thresholds were monitored in 15 healthy controls and 30 functional dyspepsia patients by water load test and gastric barostat. Based on barostat the sensitivity, specificity, Kappa value, coincidence rate of water load test were evaluated and the correlation between those two methods was assessed. RESULTS: Compared with gastric barostat, the sensitivity, specificity, Kappa value and coincidence rate of water load test for evaluating perception thresholds were reached 85.7%, 93.5%, 0.82, and 91.1%. These of water load test for evaluating discomfort thresholds were reached 81.8%, 91.2%, 0.79, and 88.9% compared with gastric barostat. The results were showed a good correlation between water load test and gastric barostat (P < 0.01, respectively). CONCLUSIONS: It had higher specificity, Kappa value and coincidence rate of water load test for evaluating the sensation threshold compared with gastric barostat. It can be applied effectively in clinical diagnosis for evaluating the sensory threshold.