The development and initial validation of IgG4-related disease damage index: a consensus report from Chinese IgG4-RD Consortium.

OBJECTIVE: To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI). METHODS: A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters. RESULTS: IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91). CONCLUSION: The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.

Preoperative H. pylori Eradication Therapy Facilitates Precise Delineation in Early Gastric Cancer with Current H. pylori Infection.

INTRODUCTION: Early gastric cancer with current Helicobacter pylori infection (HpC-EGC) is common, but it is still unclear whether H. pylori eradication therapy (Hp-ET) or endoscopic submucosal dissection (ESD) should be performed first. We evaluated Hp-ETs short-term effects on horizontal boundary delineations of HpC-EGC in ESD. METHODS: Prospectively enrolled HpC-EGC patients were randomly assigned to eradication or control groups. Operation scopes of HpC-EGC lesions were delineated with marking dots at 5 mm out of the endoscopic demarcation line by an independent endoscopist, unaware of eradication status, before formal circumferential incision. As representatives, precise delineation rate, the shortest distance of all marking dots to the pathological demarcation line in all slices of one intact resected specimen (Dmin), and negative marking dot specimen rate were examined. RESULTS: Twenty-three HpC-EGC patients (25 lesions) were allocated to eradication group and 26 patients (27 lesions) were allocated to the control group with similar eradication success rates and all were differentiated type. With improving background mucosa inflammation after Hp-ET and similar gastritis-like epithelium rates, 10 lesions (40.0%) in the eradication group were of precise delineation compared to control group with 2 lesions (7.4%) (relative risk = 5.40, 95% CI 1.31-22.28). Dmin of eradication and control groups were 4.17 ± 2.52 mm and 2.67 ± 2.30 mm (p = 0.029), accompanied by 4 (14.8%) and none (0.0%) specimens that exhibited positive marking dots (p = 0.11), respectively. CONCLUSION: For HpC-EGC patients, administrating eradication medication before ESD is beneficial for the precise delineation of lesions and reducing the risk of positive horizontal resection margins.

Acquired von Willebrand Syndrome Secondary to Normally Functioning Mechanical Aortic Valve and High-Output Cardiac State.

Acquired von Willebrand syndrome (AVWS) is caused by an acquired deficiency of von Willebrand factor (VWF), a multimeric protein required for primary hemostasis. For patients with heart valve diseases, high gradient across the malfunctioning valves could cause elevated shear stress and damage the most effective large VWF, eventually resulting in AVWS. However, AVWS has not been reported in association with normally functioning mechanical valves. Herein, we reported a 74-year-old female who suffered from recurrent gastrointestinal bleeding with a history of mechanical aortic and mitral valve replacement. This patient's function/antigen ratio of VWF was decreased and gel electrophoresis revealed the loss of large VWF, which confirmed the diagnosis of AVWS. Echocardiogram showed that the function of the prostheses was normal. However, the gradient across aortic valve was increased due to a high cardiac state which is secondary to chronic anemia, resulting in the disruption of large VWF multimers and exacerbation of gastrointestinal (GI) bleeding. After managing the patient's anemia with transfusion, the gradient across the aortic valve had improved, with the resolution of GI bleeding. This is the first case report of AVWS that is associated with a normally functioning mechanical valve. AVWS should be considered one of the differential diagnoses if patients present with unexplained GI bleeding on the background of having prosthetic heart valves. The management of the underlying condition is essential.

Computed tomography enterography increases the ability of endoscopy to differentiate Crohn's disease from intestinal Behçet's disease.

Background: Distinguishing Crohn's disease (CD) and intestinal Behçet's disease (BD) is difficult in clinical practice. Aim: To evaluate the ability of CT enterography (CTE) to enhance the diagnostic value of endoscopy in differentiating CD from intestinal BD and to establish differential diagnosis models. Methods: A total of 113 patients with CD and 70 patients with intestinal BD from seven tertiary inflammatory bowel disease centers were enrolled. The univariate and multivariate analyses were used by SAS software version 9.2. Three differential scoring models based on the multivariate analysis of endoscopic features alone (model 1), endoscopic features combined with clinical symptoms (model 2), and endoscopic features combined with clinical symptoms and CTE (model 3) were established. Results: The results showed that model 2 increased the efficacy of model 1 in differential diagnosis and model 3 had the highest accuracy of 84.15% at a cutoff value of two points. The scoring of model 3 was as follows: genital ulcer (-3 points), skin lesions (-3 points), oval ulcer (-2 points), longitudinal ulcer (1 point), number of ulcers > 5 (3 points), inflammatory polyps (2 points), mucosal severe enhancement (2 points), and fibrofatty proliferation (1 point). Conclusion: Clinical symptoms and CTE increased the ability of endoscopy to differentiate CD from intestinal BD.

[SAPHO Syndrome Complicated with Ulcerative Colitis:Report of One Case].

Synovitis,acne,pustulosis,hyperostosis,and osteitis (SAPHO) syndrome is a rare disease. The previous literature demonstrated that about 10% of the patients with SAPHO syndrome were complicated with inflammatory bowel disease.So far,few cases of SAPHO syndrome complicated with inflammatory bowel disease have been reported in China.Herein,we reported a SAPHO syndrome case complicated with ulcerative colitis. The patient suffered from recurrent attacks of colitis following treatment of SAPHO syndrome with etanercept.

Differential Diagnosis of Crohn's Disease and Ulcerative Primary Intestinal Lymphoma: A Scoring Model Based on a Multicenter Study.

Background: Differential diagnosis of Crohn's disease (CD) and ulcerative primary intestinal lymphoma (UPIL) is a tough problem in clinical practice. Aims: Our study identified key differences between CD and UPIL patients and aimed to further establish a scoring model for differential diagnosis. Methods: A total of 91 CD and 50 UPIL patients from 9 tertiary inflammatory bowel disease centers were included. Univariate and multivariate analyses were used to determine significant markers for differentiating CD and UPIL. A differential scoring model was established by logistic regression analysis. Results: The differential model was based on clinical symptoms, endoscopic and imaging features that were assigned different scores: intestinal bleeding (-2 points), extraintestinal manifestation (2 points), segmental lesions (1 point), cobblestone sign (2 points), homogeneous enhancement (-1 point), mild enhancement (-1 point), engorged vasa recta (1 point). A total score of ≥1 point indicates CD, otherwise UPIL was indicated. This model produced an accuracy of 83.66% and an area under the ROC curve of 0.947. The area under the ROC curve for validation using the 10-fold validation method was 0.901. Conclusion: This study provided a convenient and useful model to differentiate CD from UPIL.

Persistent enlargement of the pancreatic gland after glucocorticoid therapy increases the risk of relapse in IgG4-related autoimmune pancreatitis.

OBJECTIVES: This study aims to clarify the relationship between the changes of pancreatic size after glucocorticoid (GC) therapy and relapse in IgG4-related autoimmune pancreatitis (AIP). METHODS: We prospectively enrolled 205 newly diagnosed IgG4-related AIP patients. 145 patients were followed up for more than 3 years. These patients were divided into three groups according to the changes of pancreatic size after treatment of 6 months: pancreatic swelling, normal size, and pancreatic atrophy. Baseline clinical and laboratory parameters were compared among three groups. Kaplan-Meier survival analysis was performed in the 134 patients based on GC therapy. Besides, Cox regression analysis and logistic regression analysis were performed to identify risk factors associated with relapse and the potential variables affecting changes of pancreatic size after treatment. RESULTS: Age at diagnosis, white blood cell count, and serum IgG1 level at baseline were significantly different among the three groups. After treatment of 6 months, the pancreas of most patients (n = 81, 55.9%) could return to normal size, while persistent pancreatic swelling was found in 24.1% patients (n = 35), and atrophy was observed in 20.0% of the patients (n = 29). Kaplan-Meier survival analysis presented patients with pancreatic swelling after 6 months of GC therapy were more likely to relapse in the follow-up of 3 years. Persistent pancreatic swelling after treatment and salivary gland involvement at baseline were independent risk variables associated with relapse in IgG4-related AIP patients, while GC-based therapy was a protective factor of relapse. Logistic regression analysis revealed that older age at diagnosis was associated with pancreatic atrophy and higher baseline serum IgG1 level was associated with pancreatic swelling after treatment of 6 months. CONCLUSIONS: Patients with persistent pancreatic swelling after GC-based therapy of 6 months were more likely to relapse in the follow-up of 3 years. Older age at diagnosis and higher baseline serum IgG1 level were potential variables associated with pancreatic atrophy or swelling after treatment of 6 months. Key Points • Patients with persistent pancreatic swelling after glucocorticoid-based therapy were more likely to relapse in IgG4-related autoimmune pancreatitis. • Older age at diagnosis was associated with pancreatic atrophy after glucocorticoid-based therapy. • Higher baseline serum IgG1 level was associated pancreatic swelling after glucocorticoid-based therapy.

Calcium and pH value might predict persistent renal failure in acute pancreatitis in the early phase.

OBJECTIVES: Persistent renal failure (PRF) increases morbidity and mortality in acute pancreatitis (AP). Traditional scoring systems achieve good diagnostic value of AP but not PRF alone. Our study aimed to determine PRF predictors in AP patients for early intervention in the disease development. METHODS: In the prospective observational study, we consecutively recruited AP patients from October 2013 to October 2016. Complete clinical characteristics on admission were collected. The 2012 revision of the Atlanta classification diagnosed AP, and the Modified Marshall scoring system defined organ failures. We used univariate and multivariate analyses to select risk factors, and plotted survival curves of different groups and ROC curves of parameters to analyze PRF predictors in AP. RESULTS: A total of 29 AP patients with PRF and 280 AP patients without PRF were included. Severity scoring and ICU admission rate were higher in the former group. The PRF group's mortality was 10-fold higher than without PRF (20.7% versus 2.1%, p < .001). Most relevant kidney metabolism indicators and excretion have significant differences (p < .05) between the two groups. Serum calcium (Ca) and pH value (pH) were independent risk factors of PRF (p < .05). ROC curve analysis indicated Ca and pH might predict PRF in AP with areas under the curves (AUCs) of 0.758 and 0.809. CONCLUSIONS: AP patients with PRF had higher morbidity and mortality rate. Our study showed that Ca < 1.94 mmol/L and pH < 7.37 when patients on admission could be used to predict PRF in AP.

Endoscopic ultrasound features of autoimmune pancreatitis: The typical findings and chronic pancreatitis changes.

BACKGROUND: Few studies have fully described endoscopic ultrasound (EUS) features of newly diagnosed autoimmune pancreatitis (AIP) involving both typical findings and chronic pancreatitis (CP) features. The typical EUS findings are prevalent in the diffuse type AIP but may not be as common for the focal type, and the differences between the diffuse and focal AIP need to be specified. AIM: To demonstrate the EUS features of newly diagnosed AIP and the difference between diffuse and focal AIP. METHODS: This retrospective single center study included 285 patients of newly diagnosed type 1 AIP following the international consensus diagnostic criteria, with the EUS procedures accomplished before corticosteroid initiation. We explored the EUS features and compared the typical AIP and CP features between the diffuse and focal AIP cases. The Rosemont criteria were employed for CP features definition and CP change level comparison. RESULTS: For the typical AIP features, there were significantly more patients in the diffuse group with bile duct wall thickening (158 of 214 cases, 73.4% vs 37 of 71 cases, 52.1%, P = 0.001) and peripancreatic hypoechoic margin (76 of 214 cases, 35.5% vs 5 of 71 cases, 7.0%, P < 0.001). For the CP features, there were significantly more patients in the focal group with main pancreatic duct dilation (30 of 214 cases, 14.0% vs 18 of 71 cases, 25.3%, P = 0.03). The cholangitis-like changes were more prevalent in the focal cases with pancreatic head involvement. The CP change level was relatively limited for newly diagnosed AIP cases in both groups. CONCLUSION: This study demonstrated the difference in the typical AIP and CP features between diffuse and focal AIP and indicated the limited CP change level in newly diagnosed AIP.

The role of EUS in diagnosing focal autoimmune pancreatitis and differentiating it from pancreatic cancer.

BACKGROUND AND OBJECTIVES: The clinical presentation of focal autoimmune pancreatitis (FAIP) and together with radiological overlap can mimic pancreatic cancer (PC). The aim of this study is to construct and validate a prediction model for differentiating FAIP from PC according to EUS characteristics. PATIENTS AND METHODS: Ninety patients with FAIP and 196 patients with PC, who consecutively underwent EUS at our center from January 2013 to December 2018, were retrospectively included in the study. The enrolled patients were randomly divided into either a derivation sample or a validation sample. According to EUS characteristics, multivariate stepwise logistic regression and receiver operating characteristics (ROC) analyses were used to construct a prediction model in derivation sample, and then, the efficacy was assessed in validation sample. RESULTS: EUS characteristics that were suggestive of FAIP included diffuse hypoechogenicity, hyperechoic foci/stands or lobularity (parenchymal heterogeneity), bile duct wall thickening and peripancreatic hypoechoic margin; and EUS features favoring PC included focal hypoechogenicity, absence of parenchymal heterogeneity, pancreatic duct dilation, and vessel involvement. The prediction model, with an area under the ROC curve of more than 0.95, had a good capability to distinguish FAIP from PC. By using the optimal cutoff value, the efficacy of model for diagnosing PC showed 83.7%-91.8% sensitivity and 93.3%-95.6% specificity. CONCLUSIONS: It is feasible to differentiate FAIP from PC based on EUS characteristics. The prediction model built in this study needs to be further confirmed by multicenter prospective researches.

DWI of Autoimmune Pancreatitis: Is It an Imaging Biomarker for Disease Activity?

OBJECTIVE. The purpose of this article was to evaluate the DWI features of autoimmune pancreatitis (AIP) at baseline, under treatment, and at relapse, and to assess the diagnostic accuracy of the ADC for determining disease activity. MATERIALS AND METHODS. This retrospective study was approved by the institutional review board. Sixty-two patients with AIP (48 at initial attack and 14 at relapse) underwent MRI with DWI (b = 0 and 800 s/mm2) at 3 T before receiving corticosteroid therapy (CST) and during follow-up. Seventeen patients had disease relapse during follow-up, whereas the others remained clinically stable. Forty age- and sex-matched patients without pancreatic disease served as the control group. RESULTS. The ADC value of AIP at baseline was significantly lower than that for a disease-free pancreas (0.99 ± 0.12 vs 1.26 ± 0.10 × 10-3 mm2/s, p < .001). Under CST, the ADC value increased gradually at the short-term and long-term follow-up (1.16 ± 0.12 and 1.23 ± 0.12 × 10-3 mm2/s, respectively, both p < .001). At relapse, the ADC had a relative decrease (1.11 ± 0.20 × 10-3 mm2/s) but was significantly higher compared with the initial attack (p = .003). The AUC of ADC serum IgG4 level at ROC analysis for baseline versus clinically stable AIP was 0.867 and 0.700, the AUC for clinically active AIP versus clinically stable AIP was 0.762 and 0.686, and the AUC for relapsed AIP versus clinically stable AIP was 0.648 and 0.669. CONCLUSION. DWI reflected the dynamic change of AIP under CST, and the ADC value for DWI outperformed the serum IgG4 value for determining disease activity. However, relapsed disease showed less diffusion restriction, and the ADC value was less accurate for predicting relapse.

A 16-year trend of etiology in acute pancreatitis: The increasing proportion of hypertriglyceridemia-associated acute pancreatitis and its adverse effect on prognosis.

BACKGROUND: Acute pancreatitis (AP) is an acute inflammation of the pancreas, which caused increasing global health and economic burden. Longitudinal trends of disease etiology and its influence on prognosis remains unclear. OBJECTIVE: The aim of this study was to analyze the trend of etiology in moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) and to evaluate the influence of the changing pattern of etiology. METHODS: A 16-year cohort study was undertaken in a tertiary hospital. Patients who presented with MSAP or SAP from January 2001 to December 2016 were continuously enrolled. Demographic data, clinical manifestations, treatment strategy, and prognosis were recorded and verified. RESULTS: A total of 475 patients were included, among whom 173 (36.4%) had gallstone-associated pancreatitis and 108 (22.7%) had hypertriglyceridemia (HTG)-associated pancreatitis. The annual admission for MSAP and SAP rose steadily over the 16-year period (r = 0.907, P < .001), with an annually increasing proportion of HTG-associated pancreatitis (from 14.3% to 35.5%, r = 0.710, P = .015). Compared with gallstone-associated pancreatitis, hypertriglyceridemia-associated pancreatitis had significantly higher percentages of multiple organ dysfunction syndrome (MODS) (24.1% vs 12.1%, P = .009, FDR = 0.029) and cardiovascular failure (17.6% vs 4.6%, P < .001, FDR<0.001). Positive correlations were found between the annual proportion of HTG-associated pancreatitis and MODS (r = 0.574, P = .005) and between HTG-associated pancreatitis and cardiovascular failure (r = 0.512, P = .029). Regression analysis showed that HTG was an independent risk factor for both MODS (P = .004) and cardiovascular failure (P = .009). CONCLUSIONS: The number of annually admitted MSAP and SAP cases increased during the last 16 years along with an increasing proportion of HTG-associated AP. The increasing trend of HTG-associated AP might contribute to more frequently occurring MODS and cardiovascular failure.

Pancreaticobiliary involvement in treated type 1 autoimmune pancreatitis: Imaging pattern and risk factors for disease relapse.

PURPOSE: To evaluate the imaging pattern of pancreaticobiliary lesions in patients with treated type 1AIP, to determine the incidence of disease relapse and malignancy, and to identify the risk factors. METHOD: The institutional review board approval was acquired. All patients gave written informed consent. From a prospective clinico-radiological database since 2012, consecutive patients with type 1 AIP who were treated and followed up (≥18 months) were identified. The presence/absence of pancreaticobiliary lesion(s) development during follow-up were assessed. The etiology was determined and the imaging pattern was compared to the initial attack. Risk factors were identified by univariate and multivariate analysis. RESULTS: Among 103 patients with treated type 1 AIP, 44 (42.7%) developed pancreaticobiliary lesions during follow up (median time interval to initial diagnosis: 17 months, range 3-62 months), mostly after steroid discontinuation (63.6%) or during maintenance therapy (29.5%). All lesions were disease relapse, which responded to steroid treatment. At relapse, pancreatic involvement was less frequent (81.8% vs 100%, p = 0.003), and the pancreas size was smaller (p < 0.01), whereas extra-pancreatic bile duct (ExPanBD) involvement was more severe and extensive (both p < 0.01). Multivariate analysis revealed ExPanBD involvement at initial diagnosis (hazard ratio 2.437, 95% CI 1.343-7.402, p = 0.002) and serum IgG4 response ratio at the induction phase (hazard ratio 0.357, 95% CI 0.055-0.804, p = 0.011) as significant independent predictors of relapse. CONCLUSIONS: In treated type 1 AIP, although imaging pattern may differ, pancreaticobiliary lesions are usually manifestations of disease relapse. ExPanBD involvement and poor serum response suggests high risk of relapse.

Differences and similarities between IgG4-related disease with and without dacryoadenitis and sialoadenitis: clinical manifestations and treatment efficacy.

BACKGROUND: This study aimed to compare the differences and similarities in the clinical manifestations and treatment efficacy of IgG4-related disease (IgG4-RD) in patients with and without dacryoadenitis and sialoadenitis (DS). METHODS: A total of 121 untreated IgG4-RD patients in Peking Union Medical College Hospital were enrolled in this study. The patients were divided into three groups: DS-predominant (group A), non-DS (group B), and DS with other internal organs affected (group C). The patients were followed up for at least 15 months. Baseline and follow-up data were collected. The disease activity was evaluated according to the IgG4-RD responder index. RESULTS: The mean ± SD age at disease onset was 53.2 ± 14.1 years, and 71.9% of the patients were male. The prevalence of allergies was higher in groups A (21, 61.8%) and C (32, 69.6%) than group B (14, 34.1%). More patients with DS (17, 50.0%, and 17, 37.0%) had sinonasal lesions than those without DS (5, 12.2%). Moreover, an increased number of eosinophils were more common in patients with DS than in those without, as were increased serum IgG, IgG4, and IgE levels. More patients in group B and group C (28, 68.3%, and 31, 67.4%) received a combination therapy of corticosteroid and immunosuppressant. During the 15-month follow-up, 28 (23.1%) patients had disease relapse. CONCLUSION: Results demonstrated that IgG4-RD patients with DS had distinctive clinical features compared with non-DS. Allergy and sinonasal involvement were more common in patients with DS. Patients with DS showed higher serum IgG4 levels than those without DS.

Native T1 mapping of autoimmune pancreatitis as a quantitative outcome surrogate.

OBJECTIVES: To investigate the ability of T1 mapping to visualize and quantify the short-term and mid-term response of autoimmune pancreatitis (AIP) to corticosteroid treatment (CST) and to correlate T1 relaxation time of the pancreas with clinical status and serum IgG4 level. METHODS: The institutional review board approved this prospective study, and all patients provided written informed consent. Pancreatic MRI including native T1 mapping was performed in 39 AIP patients before and during CST, and 40 patients without pancreatic diseases served as control. T1 relaxation time of the pancreatic head, body, and tail was measured in each patient. Clinical symptoms and serum IgG4 level of the patients were recorded. RESULTS: The native T1 relaxation time of AIP was significantly elongated compared to normal pancreatic tissue (1124.5 ms ± 95.7 ms vs 784.3 ms ± 41.8 ms, p < 0.001). After short-term CST (4 weeks), T1 relaxation time of AIP already shortened significantly (957.2 ms ± 97.3 ms, p < 0.001). After mid-term CST (12 weeks), the T1 relaxation time further shortened towards normalization (844.2 ms ± 71.6 ms, p < 0.001). In 33 AIP patients with elevated serum IgG4 at baseline, T1 relaxation time demonstrated a significant positive correlation with serum IgG4 level (r = 0.329, p = 0.011). In six AIP patients with normal serum IgG4 level at baseline, T1 relaxation time shortening preceded or was in accordance with symptom relief. CONCLUSIONS: Native T1 mapping can be used to assess parenchymal inflammation of AIP and to quantify response to treatment. It provides a quantitative outcome surrogate for AIP. KEY POINTS: • Parenchymal inflammation in autoimmune pancreatitis results in T1 relaxation time elongation, which shortens after effective treatment. • T1 relaxation time of the pancreas correlates with serum IgG4 level, and in serum IgG4-negative AIP patients, T1 relaxation time shortening predicts clinical improvement. • T1 mapping provides a quantitative outcome surrogate for AIP.

Sex disparities in clinical characteristics and prognosis of immunoglobulin G4-related disease: a prospective study of 403 patients.

OBJECTIVES: To study the impact of sex on the clinical presentation of IgG4-related disease (IgG4-RD). METHODS: We prospectively enrolled 403 newly diagnosed IgG4-RD patients. We compared the demographic features, clinical manifestations, organ involvement, laboratory tests and treatment outcomes between female and male patients. The organs involved were divided into superficial organs (salivary glands, lacrimal glands, orbit, sinus and skin) and internal organs (all the other organs). The patients treated with glucocorticoids with or without additional immunosuppressants were included in the assessment of treatment outcomes, and potential confounding factors were corrected by propensity score matching or multivariate Cox regression analysis. RESULTS: Female patients showed younger age at both symptom onset and diagnosis, and a longer interval between symptom onset and diagnosis. Allergy history, Mikulicz's disease and thyroiditis were more common in female patients, while autoimmune pancreatitis, sclerosing cholangitis and retroperitoneal fibrosis were more common in male patients. In accordance, female patients more frequently presented with superficial organ involvement, while male patients more frequently had internal organ involvement, and the discrepancy was more prominent in the patients with older age. Male sex was associated with higher peripheral eosinophils, CRP and IgG4 levels at baseline. In response to glucocorticoid-based therapies, male sex was associated with a higher IgG4-RD responder index during follow-up as well as a greater risk of relapse (hazard ratio 3.14, P = 0.003). CONCLUSION: Our study revealed the sex disparities in clinical characteristics of IgG4-RD, and indicated that male sex was independently associated with worse prognosis in response to glucocorticoid-based therapies.

Failure of remission induction by glucocorticoids alone or in combination with immunosuppressive agents in IgG4-related disease: a prospective study of 215 patients.

BACKGROUND: The aim of this study was to assess the outcomes of remission induction in patients with IgG4-related disease (IgG4-RD) in our cohort, and to investigate the characteristics, prognosis, and risk factors in the patients failed of remission induction. METHODS: We prospectively enrolled 215 newly diagnosed patients with IgG4-RD, who were initially treated with glucocorticoid (GC) alone or in combination with immunosuppressive agents (IM), and had at least 6 months of follow up. The therapeutic goals of remission induction were defined as fulfilling each of the following after the 6-month remission induction stage: (1) ≥ 50% decline in the IgG4-RD responder index (RI); (2) GC tapered to maintenance dose; and (3) no relapse during GC tapering. The patients not achieving the therapeutic goals were considered to have failed of remission induction. RESULTS: There were 26 patients in our cohort who failed of remission induction, including 16 (20.8%) on GC monotherapy, and 10 (7.2%) on combination therapy comprising GC and IM. The lacrimal gland and lung were most common sites of remission induction failure. Among the patients who relapsed during remission induction stage, 52.9% had secondary relapse during follow-up. Eosinophilia, higher baseline RI, more than five organs involved and dacryoadenitis were risk factors for remission induction failure with GC monotherapy, and the incidence of remission induction failure was 71.4% in the patients with more than three risk factors. After 6-month treatment, the patients who failed of remission induction had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and IgG4. CONCLUSION: In our cohort, 20.8% of patients failed of remission induction with GC monotherapy, while 7.2% of patients failed of remission induction with combination therapy comprising GC and IM.

Establishment and Verification of a Scoring Model for the Differential Diagnosis of Pancreatic Cancer and Chronic Pancreatitis.

OBJECTIVES: The aims of this study were to establish a scoring model for the differential diagnosis of pancreatic cancer (PC) and chronic pancreatitis (CP) and to evaluate its diagnostic efficacy. METHODS: The data of 502 patients with PC and 210 patients with CP at the Peking Union Medical College Hospital from January 1999 to December 2013 were retrospectively analyzed. Binary logistic regression was applied to establish the prediction model for the differential diagnosis. The model was verified using the method of leave-one-out cross-validation. RESULTS: The scoring system was established with 5 variables including age, carbohydrate antigen 19-9 level, splenic vein invasion, irregular dilatation of the pancreatic duct, and nontruncated pancreatic duct stenosis. The score range was from -2 to 3. The area under the receiver operating characteristic curve of the objects was 0.779 (95% confidence interval, 0.744-0.814) (P < 0.01), indicating that the scoring system is good at differentiation of PC with CP. With a score of 1 as the diagnostic cut-off value, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate were 71.3%, 69.0%, 70.0%, 71.4%, and 70.2%, respectively. CONCLUSIONS: The scoring model may improve the differential diagnosis of PC and CP and be useful in clinical practice.

Model to identify early-stage gastric cancers with deep invasion of submucosa based on endoscopy and endoscopic ultrasonography findings.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Ocular manifestations as first signs of systemic T cell lymphoma in two cases.

BACKGROUND: Intraocular involvement of systemic T-cell lymphomas are uncommon and have been broadly regarded as markers of poor prognosis. We reported two cases of uveitis patients finally diagnosed as systemic T cell lymphoma. CASE PRESENTATION: Case one is a 19-year-old female presented with fever and liver dysfunction, and was diagnosed as EBV-associated chronic active hepatitis. Fourteen months later, she suffered from recurrent granulomatous anterior uveitis in both eyes, which failed to respond to steroid and immunosuppressant therapy. A mass on the left side of pharynx was found and the final diagnosis was pharynx T cell non-Hodgkin's lymphoma. After 13 cycles of chemotherapy, her systematic symptoms and uveitis relieved a lot, and eye condition is stable after cataract surgery. Case two is a 37-year-old male complaining bilateral blurred vision and recurrent abdominal pain. Panuveitis was diagnosed and anterior inflammation did not release after topical steroid. During the following days, the patient complained intermittent abdominal pain and fever, with rapidly progressive bilateral visual decrease. Final diagnosis was gallbladder type II enteropathy-associated T-cell lymphoma. The patient died of multiple organ failure 4 days after operation that was only 26 days after presenting to our hospital. CONCLUSIONS: Ocular manifestations as first signs of systemic T cell lymphoma were rare. Diagnosis of lymphoma has to be suspected when patients have systemic manifestations including fever, fatigue, abdominal pain, EBV-associated liver disease, et al., and uveitis fails to respond to steroid therapy.