MLH1 Inhibits Metastatic Potential of Pancreatic Ductal Adenocarcinoma via Downregulation of GPRC5C.

DNA mismatch repair gene MutL homolog-1 (MLH1) has divergent effects in many cancers; however, its impact on the metastasis of pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, MLH1 stably overexpressed (OE) and knockdowned (KD) sublines were established. Wound healing and transwell assays were used to evaluate cell migration/invasion. In vivo metastasis was investigated in orthotopic implantation models (severe combined immunodeficiency mice). RT-qPCR and western blotting were adopted to show gene/protein expression. MLH1 downstream genes were screened by transcriptome sequencing. Tissue microarray-based immunohistochemistry was applied to determine protein expression in human specimens. In successfully generated sublines, OE cells presented weaker migration/invasion abilities, compared with controls, whereas in KD cells, these abilities were significantly stronger. The metastasis-inhibitory effect of MLH1 was also observed in mice. Mechanistically, G protein-coupled receptor, family C, group 5, member C (GPRC5C) was a key downstream gene of MLH1 in PDAC cells. Subsequently, transient GPRC5C silencing effectively inhibited cell migration/invasion and remarkably reversed the proinvasive effect of MLH1 knockdown in KD cells. In animal models and human PDAC tissues, tumoral GPRC5C expression, negatively associated with MLH1 expressions, was positively correlated with histologic grade, vessel invasion, and poor cancer-specific survival. In conclusion, MLH1 inhibits the metastatic potential of PDAC via downregulation of GPRC5C.

An MMP-based risk score strongly distinguishes prognosis in hepatocellular carcinoma after resection.

Aim: To first explore the prognostic value of MMP11 and MMP15 in hepatocellular carcinoma. Methods: MMP11/MMP15 expression was immunohistochemically detected and correlated with clinicopathologic variables and survival and confirmed in publicly available databases. An MMP-based risk score (MMPRS) was established. Results: Tumoral MMP11/MMP15 expression was higher and univariately associated with crucial clinicopathologic parameters, overall survival and disease-free survival in all patients and/or many subsets. Multivariately, MMP11/MMP15 expression remained significant. Their overexpression and prognostic value were confirmed in the Ualcan and Kaplan-Meier plotter databases. Critically, the novel MMPRS integrating MMP11, MMP15 and tumor-node-metastasis stage identified subgroups with the best and worst prognoses, with much higher predictive power. Conclusion: MMP11 and MMP15 served as prognosticators in hepatocellular carcinoma. MMPRS might work more accurately.

MMP11 and MMP15, involved in cancer dissemination, were found to have important biological functions in several cancers. However, their prognostic value in hepatocellular carcinoma (HCC) remains unknown. In the present study, it was found that MMP11 and MMP15 were overexpressed and predictive of the outcome of HCC. Moreover, the novel MMP-based risk score integrating MMP11, MMP15 and tumor­node­metastasis stage had much higher prognostic power. MMP11, MMP15 and especially the MMP-based risk score were identified as promising indicators of prognosis in HCC.

Can Endorectal Ultrasound, MRI, and Mucosa Integrity Accurately Predict the Complete Response for Mid-Low Rectal Cancer After Preoperative Chemoradiation? A Prospective Observational Study from a Single Medical Center.

BACKGROUND: Patients with locally advanced rectal cancer could be managed by a watch-and-wait approach if they achieve clinical complete response after preoperative chemoradiotherapy. Mucosal integrity, endorectal ultrasound, and rectal MRI are used to evaluate clinical complete response; however, the accuracy remains questionable. Clinical practice based on those assessment methods needs more data and discussion. OBJECTIVE: The aim of this prospective study was to evaluate the accuracy of mucosal integrity, endorectal ultrasound, and rectal MRI to predict clinical complete response after chemoradiotherapy. DESIGN: Endorectal ultrasound and rectal MRI were undertaken 6 to 7 weeks after preoperative chemoradiation therapy. Patients then received radical surgery based on the principles of total mesorectal excision. Preoperative tumor staging achieved by endorectal ultrasound and rectal MRI was compared with postoperative staging by pathologic examination. Sensitivity, specificity, and accuracy of each evaluation method were calculated. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: Patients diagnosed with mid-low rectal cancer by biopsy between May 2014 and December 2016 were enrolled in this study. RESULTS: A total of 124 patients were enrolled in this study, and postoperative pathology revealed that 20 patients (16.13%) achieved complete response (ypT0N0). The sensitivity of mucosal integrity, endorectal ultrasound, and MRI to predict clinical complete response was 25%. The specificity of mucosal integrity, endorectal ultrasound, and MRI was 94.23%, 93.90%, and 93.27%. The combination of each 2 or all 3 methods did not improve accuracy. Regression analysis showed that none of these methods could predict postoperative ypT0. LIMITATIONS: The sample size is small, and we did not focus on the follow-up data and cannot compare prognosis data with previous research studies. CONCLUSIONS: Both single-method and combined mucosal integrity, endorectal ultrasound, and rectal MRI have poor correlation with postoperative pathologic examination. A watch-and-wait approach based on these methods might not be a proper strategy compared with radical surgery after neoadjuvant therapy. See Video Abstract at http://links.lww.com/DCR/A693.

High nuclear Survivin expression as a poor prognostic marker in pancreatic ductal adenocarcinoma.

BACKGROUND: Survivin, one of the key regulators of mitosis and apoptosis, has long been well recognized to play important biological roles in many neoplasms, including pancreatic ductal adenocarcinoma (PDAC). However, its prognostic value in PDAC remains controversial. PATIENTS AND METHODS: Nuclear expression of Survivin was detected, using tissue microarray-based immunohistochemistry, in paired-tumor and nontumor samples from 306 patients with radically resected PDAC. The staining H scores were further correlated with clinicopathologic features and disease-specific survival (DSS). RESULTS: Nuclear Survivin expression was much higher in tumor than in nontumor tissues (P < 0.001). No significant association between tumoral Survivin expression and clinicopathologic variables was found. For prognosis, high Survivin expression was associated with shortened DSS in all eligible patients and four subgroups, that is, male and nondiabetic patients as well as those with head-located and G1-2 tumors, shown by univariate analyses. In addition, a statistically marginal significance was revealed in eight subgroups. For the entire cohort and two subgroups, nuclear Survivin expression was also multivariate identified as an independent predictor for DSS. For patients with G1-2 tumors, it was the single prognostic marker. CONCLUSION: Our data suggest an association between high nuclear Survivin expression and poor prognosis in PDAC. However, further confirmation might be necessary.

[Clinical Features and Outcomes of Paraduodenal Pancreatitis].

Objective To summarize the clinical features and outcomes of paraduodenal pancreatitis (PP). Methods Five clinically or pathologically diagnosed PP patients in Peking Union Medical College Hospital and 31 other PP cases reported in Chinese literature since 1988 were retrospectively analysed. Results Most PP patients were young or middle-aged males with a history of alcohol abuse. The clinical symptoms included upper abdominal pain,vomiting,weight loss,and fluctuating jaundice. Serum pancreatic enzymes were normal or elevated. Radiological features in most cases included thickening of the duodenal wall and duodenal stenosis (88.9%,32/36),cysts in the duodenal wall and groove area (47.2%,17/36),dilated bile duct (36.1%,13/36),and dilated pancreatic duct (16.7%,6/36). The main pathological finding was chronic pancreatitis,which could be accompanied by local acute inflammation,which was limited in the groove-duodenal area in most cases. The disease can be well controlled by conservative treatment,although surgery was needed in a small number of cases. Conclusion sPP typically occurs in young or middle-aged males. Radiological examination is valuable for diagnosis. Conservative treatment is the mainstream treatment in most patients.

Correlation between Ultrasound-guided Diffuse Optical Tomography and Hypoxia-inducible Factor-1Α of Breast Cancer.

Objective To investigate the correlation between ultrasound-guided diffuse optical tomography (US-DOT) and hypoxia-inducible factor-1Α (HIF-1Α) of breast cancer. Methods Totally 69 patients with pathologically confirmed breast cancer underwent preoperative conventional breast ultrasonography examinations and US-DOT at Peking Union Medical College Hospital From October 2007 to February 2010 were enrolled in this study.After surgery,immunohistochemical staining of HIF-1Α and CD34 were performed,and the differences of total hemoglobin concentration (THC) and microvessel density (MVD) between HIF-1Α positive and negative groups were analyzed. Results HIF-1Α was positive in 12 cases (17.4%) and negative in 57 cases (82.6%). The average THC and MVD of HIF-1Α-positive cases were (274.763±77.661) Μmol/L and (33.8±10.8)/0.2 mm(2) respectively. The average THC and MVD of HIF-1Α-negative cases were (228.059±65.760)Μmol/L and (28.4±7.4)/0.2 mm(2). MVD(t=2.049,P=0.04) and THC(t=2.167,P=0.034) of HIF-1Α-positive group were significantly higher than those of HIF-1Α-negative group. Conclusions HIF-1Α can promote tumor angiogenesis and thus increase the blood supply and THC. As an indicator of tumor blood supply,THC can indirectly reflect the angiogenic activity of breast cancer.

Whole genome expression profiling of gastric high-grade intraepithelial neoplasia with or without cancer.

OBJECTIVE: To investigate the whole genome expression profiles between gastric high-grade intraepithelial neoplasia (HGIN) tissues with cancer and HGIN tissues without cancer. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected at Peking Union Medical College Hospital from March 2010 to May 2013. Each of the forceps biopsies from the 21 patients was HGIN,but there were 10 HGIN and 11 HGIN with cancer after the endoscopic submucosal dissection. The whole genome expression profiling was performed on 10 HGIN samples and 11 HGIN with cancer 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. RESULTS: The gene expression patterns were different between HGIN tissues with cancer and HGIN tissues without cancer. There were 470 significantly differentially expressed transcripts between them (P<0.05,Fold Change>2), with 180 up-regulated genes and 290 down-regulated genes in HGIN tissues with cancer. A GO enrichment analysis demonstrated that the most striking over-expressed transcripts in HGIN with cancer were in the category of triglyceride biosynthetic process,acylglycerol biosynthetic process,neutral lipid biosynthetic process,glycerol ether metabolic process,organic ether metabolic process,and glycerolipid metabolic process. CONCLUSION: The change of lipid metabolism may contribute to the pathogenesis of gastric cancer at an early stage.

Endoscopic and histologic abnormalities of gastrointestinal tract in patients with hereditary hemochromatosis.

BACKGROUND: Patients with iron overload frequently complained of upper gastrointestinal (GI) symptoms. This study aimed to systemically evaluate the association between hereditary hemochromatosis (HH) and gut inflammation. PATIENTS AND METHODS: HH patients were identified using the ICD-9 codes. Inclusion criteria were patients with primary HH who had esophagogastroduodenoscopy (EGD) and/or colonoscopy with GI biopsies (N=39). Patients undergoing EGD with duodenal biopsy for the indication of "rule out celiac disease" were included in the control group (N=40). GI biopsy specimens were rereviewed and scored. RESULTS: Of the 39 patients with genetically confirmed primary HH in the study group, 28 (71.8%) had liver biopsy and 25 (89.3%) of them showed iron deposition. Twenty-five patients (64.1%) had EGD and 23 (59.0%) had colonoscopy. Histologic inflammation was identified in the esophagus in 2 patients (8.0%), stomach in 11 (44.0%), duodenum in 2 (8.7%), and colon in 3 (13.0%). Duodenal biopsy specimen was available for rereview in 16 patients (41.0%). Patient demographics were comparable between the 16 cases in the study group and the 40 cases in the control group. On histology, the frequency of intraepithelial lymphocytosis of small intestine was 25.5% in the HH cases versus 2.5% in controls (P=0.020). HH patients also had a greater proportion of intraepithelial neutrophil infiltration (31.2% vs. 2.5%, P=0.006) and lamina propria lymphocyte infiltration (31.2% vs. 0%, P=0.001) than controls. CONCLUSIONS: GI inflammation was common in HH patients, which from the different perspective, supports the notion that iron overload may lead to GI inflammation.

Interleukin-22 exacerbates airway inflammation induced by short-term exposure to cigarette smoke in mice.

AIM: 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. METHODS: 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. RESULTS: 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 (TGFß1 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. CONCLUSION: Exogenous rIL-22 exacerbates the airway inflammatory responses to CS exposure in part by inducing expression of several proinflammatory cytokines and CXCR3 ligands.

N-wasp in pancreatic ductal adenocarcinoma: associations with perineural invasion and poor prognosis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has long been acknowledged to have a dismal prognosis. Therefore, prognostic markers, especially molecular ones, are of interest. So far, expression of Neural Wiskott-Aldrich syndrome protein (N-WASP) and its associations with clinicopathologic variables and prognosis for patients with PDAC remain unknown. METHODS: N-WASP expression was detected by immunohistochemical staining in a tissue microarray consisted of tumor and nontumor samples from 86 patients with PDAC. The correlations of N-WASP expression with clinicopathologic features and overall survival were evaluated. In addition, risk factors of perineural invasion (PNI) were identified. RESULTS: High expression of N-WASP was more frequent in tumor than in nontumor tissues of PDAC patients (45.3 vs. 19.8%, p < 0.001). The rank of N-WASP grading was significantly higher in tumor tissues than in nontumor tissues (p = 0.048). Also, high expression of N-WASP in tumor tissues was significantly associated with PNI, and lymph node status had a marginally significant relation to tumoral N-WASP expression. Univariate analyses showed that, in addition to conventional clinicopathologic variables, including sex, histologic grade, PNI and lymph node metastasis, high tumoral N-WASP expression was an independent marker of PNI and served as a significant predictor of poor overall survival. The prognostic implication of N-WASP expression was not proven In the multivariate analysis. CONCLUSIONS: Our data showed highly up-regulated expression of N-WASP in PDAC tissues, its correlations with PNI, and its association with an unfavorable prognosis.

Prognostic significance of epidermal growth factor-like domain 7 in pancreatic cancer.

BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7 (EGFL7) in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer (PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC. METHODS: The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally, correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated. RESULTS: EGFL7 was widely expressed in all PC cell lines tested. EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues (P=0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival, accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for long-term outcome of PC. CONCLUSION: Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.

Differential expression of the inflammation-associated chemokines/cytokines in mouse lung after exposure to cigarette smoke and smoking cessation.

OBJECTIVE: To determine the changes in the airway inflammation-related cytokine/chemokine profiles after exposure to cigarette smoke (CS) and smoking cessation (SC). METHODS: A total of 18 male C57BL/6 mice were equally divided into three groups: CS group, SC group, and normal control group. The airway resistance, lung morphology, and collagen deposition around airways were determined. HE staining and Masson trichrome staining were used for histopathological analysis. The inflammatory cells in bronchoalveolar lavage fluid (BALF) were assessed. The inflammation-associated cytokines were determined using real-time PCR and immunohistochemistry. Expressions of CXCR3 ligands including the CXCL9, CXCL10, CXCL11 and other cytokines in lung tissue and BALF were also analyzed. RESULTS: The airway resistance significantly increased in both CS group and SC group when compared with the normal control group. Lung pathological scores in both CS group and SC group were also higher than that in the normal control group, while there was no significant difference between the CS group and SC group. Inflammatory cells including the neutrophils, macrophages, and lymphocytes also increased in both the CS group and SC group at both mRNA and protein levels. The mRNA levels of CXCL9, CXCL10, MMP9, and MMP12 were significantly higher in CS group and SC group than those in the normal control group (all P<0.05). The protein expression levels of CXCL9, CXCL10, CXCL11, MMP2, MMP9, MMP12, and TGF-Β1 were significantly higher in CS group and SC group than those in the normal control group (all P<0.05). Compared with the normal control group,the concentrations of CXCL9, CXCL10, CXCL11, IL-8, and TGF-Β1 in the BALF supernatants of the CS group and SC group significantly increased (P<0.05); in addition, the IL-6 and TNF-Α concentrations also increased in the CS group (both P<0.05). CONCLUSIONS: CS exposure triggers inflammatory cell flux and accumulation in the lung parenchyma and BALF. As a consequence, the inflammatory cytokines increase dramatically. After CS, the cytokines/chemokines can decrease, but is still higher than in non-smokers.

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract. Glucocorticoids remain the most common treatment method. However, disease relapse and glucocorticoid dependence remain notable problems. To date, few studies have illuminated the prognosis of EGE and risk factors for disease relapse. AIM: To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up. METHODS: This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022. Clinical records were collected and analyzed. Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival (RFS). RESULTS: EGE showed a median onset age of 38 years and a slight female predominance (56.4%). The main clinical symptoms were abdominal pain (89.1%), diarrhea (61.8%), nausea (52.7%), distension (49.1%) and vomiting (47.3%). Forty-three (78.2%) patients received glucocorticoid treatment, and compared with patients without glucocorticoid treatments, they were more likely to have elevated serum immunoglobin E (IgE) (86.8% vs 50.0%, P = 0.022) and descending duodenal involvement (62.8% vs 27.3%, P = 0.046) at diagnosis. With a median follow-up of 67 mo, all patients survived, and 56.4% had at least one relapse. Six variables at baseline might have been associated with the overall RFS rate, including age at diagnosis < 40 years [hazard ratio (HR) 2.0408, 95% confidence interval (CI): 1.0082-4.1312, P = 0.044], body mass index (BMI) > 24 kg/m2 (HR 0.3922, 95%CI: 0.1916-0.8027, P = 0.014), disease duration from symptom onset to diagnosis > 3.5 mo (HR 2.4725, 95%CI: 1.220-5.0110, P = 0.011), vomiting (HR 3.1259, 95%CI: 1.5246-6.4093, P = 0.001), total serum IgE > 300 KU/L at diagnosis (HR 0.2773, 95%CI: 0.1204-0.6384, P = 0.022) and glucocorticoid treatment (HR 6.1434, 95%CI: 2.8446-13.2676, P = 0.003). CONCLUSION: In patients with EGE, younger onset age, longer disease course, vomiting and glucocorticoid treatment were risk factors for disease relapse, whereas higher BMI and total IgE level at baseline were protective.

Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital.

BACKGROUND: Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM: To improve overall understanding of this disease's diagnosis and prognosis. METHODS: We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS: Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION: Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Low expression of PAI-2 as a novel marker of portal vein tumor thrombosis and poor prognosis in hepatocellular carcinoma.

BACKGROUND: Plasminogen activator inhibitor (PAI)-2 was previously shown to be less frequently expressed in hepatocellular carcinoma (HCC). The present study was designed to investigate the clinical, pathological, and prognostic significance of PAI-2 expression in HCC. METHODS: Expression of PAI-2 was detected immunohistochemically for specimens from 78 patients with HCC after hepatic resection and correlated with clinicopathological features and patient survival. Risk factors of portal vein tumor thrombosis (PVTT) were also analyzed. RESULTS: Positive PAI-2 staining was observed in tumor and non-tumor tissues from 21 (26.9%) and 56 (71.8%) patients, respectively. Plasminogen activator inhibitor-2 negativity in tumor tissues was significantly associated with PVTT, with a high sensitivity not only in univariate analysis but also in multivariate analysis. In addition, positive PAI-2 staining was related to smaller tumor size and prolonged patient survival. The Cox regression model identified intratumoral PAI-2 staining as an independent prognosticator in patients with HCC after resection. CONCLUSIONS: Our data demonstrated that low expression of PAI-2 serves as a novel marker of PVTT and poor prognosis in HCC.

[Expression of doublecortin-like kinase 1 in human gastric cancer and its correlation with prognosis].

OBJECTIVE: To investigate the expression of doublecortin-like kinase 1(DCLK1)in gastric cancer and its prognostic significance. METHODS: The expression of DCLK1 was examined by immunohistochemical staining of paraffin-embedded tumor specimens from 122 patients who underwent curative gastrectomy for gastric cancer at Peking Union Medical College Hospital between July 2002 and December 2006. Survival curves were described by the Kaplan-Meier method and compared by the Log-rank test. Univariate and multivariate analysis was performed with the Cox proportional hazard model. RESULTS: The expression of DCLK1 in tumor cells was significantly upregulated in 51 of 122 patients. High expression of DCLK1 in tumor cells was strongly correlated with pN stage(P=0.029)and lymphovascular invasion(P=0.029). Kaplan-Meier analysis revealed that patients with DCLK1 high expression had a significantly lower 5-year overall survival(OS)rate than that of patients with DCLK1 low expression(39. 0% vs. 65. 8%, P=0.001), as well as a significantly lower 5-year disease-free survival(DFS)rate(37. 0% vs. 64. 5%, P=0.001). Univariate and multivariate analyses showed that DCLK1 expression(both P=0.036)was an independent factor for predicting OS and DFS rate. CONCLUSIONS: High expression of DCLK1 in gastric cancer cells is associated with pN stage and lymphovascular invasion. It may be a predictor for poor survival in patients undergoing surgery for gastric cancer.

Positive correlation between latent Epstein-Barr virus infection and severity of illness in inflammatory bowel disease patients.

BACKGROUND: Emerging studies indicate the critical involvement of microorganisms, such as Epstein-Barr virus (EBV), in the pathogenesis of inflammatory bowel disease (IBD). Immunosuppressive therapies for IBD can reactivate latent EBV, complicating the clinical course of IBD. Moreover, the clinical significance of EBV expression in B lymphocytes derived from IBD patients' intestinal tissues has not been explored in detail. AIM: To explore the clinical significance of latent EBV infection in IBD patients. METHODS: Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection. Based on the staining results, the patients were divided into two groups, according to their latent EBV infection states - negative (n = 33) and positive (n = 10). Illness severity of IBD were assigned according to Crohn's disease activity index (ulcerative colitis) and Mayo staging system (Crohn's disease). The clinic-pathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups. RESULTS: Systolic pressure (P = 0.005), variety of disease (P = 0.005), the severity of illness (P = 0.002), and pre-op corticosteroids (P = 0.025) were significantly different between the EBV-negative and EBV-positive groups. Systolic pressure (P = 0.001), variety of disease (P = 0.000), pre-op corticosteroids (P = 0.011) and EBV infection (P = 0.003) were significantly different between the mild-to-moderate and severe disease groups. CONCLUSION: IBD patients with latent EBV infection may manifest more severe illnesses. It is suggested that the role of EBV in IBD development should be further investigated, latent EBV infection in patients with serious IBD should be closely monitored, and therapeutic course should be optimized.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

[Optimal surgery for breast cancer elderly patients].

OBJECTIVE: To evaluate the feasibility of optimal surgery for breast cancer in elderly patients. METHODS: The clinical data of 481 patients aged 70 years and above who were treated in our hospital from 1995 to 2009 were retrospectively analyzed. RESULTS: Based on their general conditions and clinical stages, 481 patients were divided into three groups to received different surgical procedures including modified radical mastectomy (MRM group, n=256), tumor extended resection (ER group, n=173), and simple mastectomy (SM group, n=52). The overall 5-and 10-year survival rates were 63.77%and 46.71%, respectively, and the 5-year (p=0.956) and 10-year (p=0.977) survival rates were not significantly among these three groups. However, patients in the ER group had significantly shorter hospital stay, smaller surgical wound, earlier recovery and less complications. CONCLUSION: It is feasible for female breast cancer patients over 70 years old choose the optimal surgical procedures according to their general conditions and clinical stages.

External validation of the Paddington International Virtual Electronic ChromoendoScopy ScOre as a good endoscopic score to define mucosal healing and predict long-term clinical outcomes in ulcerative colitis.

OBJECTIVES: To define endoscopic and histological remission in ulcerative colitis (UC) accurately, several scoring systems have been established. A novel virtual electronic chromoendoscopy score, the Paddington International Virtual ChromoendoScopy ScOre (PICaSSO), was developed, validated, and reproduced to assess inflammation grade and predict patient prognosis. We externally verified and validated the clinical value of PICaSSO in UC patients. METHODS: This prospective study enrolled 63 UC patients. The Mayo endoscopic score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO were adopted for endoscopic evaluation. All biopsy samples were scored using the Robarts histological index (RHI), Nancy histological index (NHI), and "Extent, Chronicity, Activity, Plus additional findings" (ECAP) score. Patients with an endoscopic MES of 0-1 at baseline were followed up during a median time of 23.5 months. RESULTS: PICaSSO was strongly correlated with other endoscopic and histological scoring systems. PICaSSO ≤3 had advantages in assessing histological remission (HR), with the highest accuracy of 88.9% for ECAP-HR. Relapse-free survival rates were significantly different between patients with MES 0 and MES 1 and patients with PICaSSO ≤3 and >3 (P = 0.010 and 0.018, respectively). CONCLUSIONS: PICaSSO was externally validated with strong correlations with other endoscopic and histological scoring systems in UC, and PICaSSO-ER might potentially predict a better long-term clinical outcome in UC patients.