Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Preliminary clinical study of personalized neoantigen vaccine therapy for microsatellite stability (MSS)-advanced colorectal cancer.

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS-CRC patients with postoperative recurrence or metastasis.

Simultaneous Imaging and Photodynamic-Enhanced Photothermal Inhibition of Cancer Cells Using a Multifunctional System Combining Indocyanine Green and Polydopamine-Preloaded Upconversion Luminescent Nanoparticles.

This work introduces a novel multifunctional system called UPIPF (upconversion-polydopamine-indocyanine-polyethylene-folic) for upconversion luminescent (UCL) imaging of cancer cells using near-infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR-triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method. To improve their biocompatibility and aqueous dispersibility, polydopamine (PDA) is introduced to the UCNP via a ligand exchange technique. Indocyanine green (ICG) molecules are electrostatically attached to the surface of the UCNP-polydopamine (UCNP@PDAs) complex to enhance the PDT and PTT effects. Moreover, polyethylene glycol (PEG)-modified folic acid (FA) is incorporated into the UCNP-polydopamine-indocyanine-green (UCNP@PDA-ICGs) nanoparticles to enhance their targeting capability against cancer cells. The excellent UCL properties of these UCNP enable the final UCNP@PDA-ICG-PEG-FA nanoparticles (referred to as UPIPF) to serve as a potential candidate for efficient anticancer drug delivery, real-time imaging, and early diagnosis of cancer cells. Furthermore, the UPIPF system exhibits PDT-assisted PTT effects, providing a convenient approach for efficient cancer cell inhibition (more than 99% of cells are killed). The prepared UPIPF system shows promise for early diagnosis and simultaneous treatment of malignant cancers.

Establishment and Validation of a Pathologic Upgrade Prediction Nomogram Model for Gastric Low-Grade Intraepithelial Neoplasia Patients After the Eradication of Helicobacter pylori.

BACKGROUND: As yet, there is no unified method of treatment for the evaluation and management of gastric low-grade intraepithelial neoplasia (LGIN) worldwide. METHODS: Patients with gastric LGIN who had been treated with Helicobacter pylori eradication were gathered retrospectively. Based on several relevant characteristics described and analyzed by LASSO regression analysis and multivariable logistic regression, a prediction nomogram model was established. C-index, the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA) were adopted to evaluate the accuracy and reliability of the model. RESULTS: A total of 309 patients with LGIN were randomly divided into the training groups and the validation groups. LASSO regression analysis and multivariable logistic regression identified that 6 variables including gender, size, location, borderline, number, and erosion were independent risk factors. The nomogram model displayed good discrimination with a C-index of .765 (95% confidence interval: .702-.828). The accuracy and reliability of the model were also verified by an AUC of .764 in the training group and .757 in the validation group. Meanwhile, the calibration curve and the DCA suggested that the predictive nomogram had promising accuracy and clinical utility. CONCLUSIONS: A predictive nomogram model was constructed and proved to be clinically applicable to identify high-risk groups with possible pathologic upgrade in patients with gastric LGIN. Since it is regarded that strengthening follow-up or endoscopic treatment of high-risk patients may contribute to improving the detection rate or reducing the incidence of gastric cancer, the predictive nomogram model provides a reliable basis for the treatment of LGIN.

Girdin influences pancreatic cancer progression by regulating c-MYC expression.

Pancreatic ductal adenocarcinoma is a complex gastrointestinal tumor with high metastatic potential and poor prognosis. Actin-binding protein Girdin is highly expressed in a variety of tumors and promotes tumorigenesis and progression. However, the mechanisms underlying the involvement of Girdin in pancreatic cancer have not been clarified. In this study, we observed that the expression of Girdin was upregulated in pancreatic cancer cells. The siRNA-mediated gene knockdown experiments showed that reduced expression of Girdin in pancreatic cancer cells inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. Functional assays revealed that c-MYC overexpression in pancreatic cancer cells could significantly increase the cell proliferation ability and rates of cell migration and invasion while decreasing the apoptosis rate. It has been shown that phosphorylation plays a role in the functional regulation of the c-MYC gene. Subsequently, we examined the expression level of c-MYC in cells with manipulated expression of Girdin and identified a positive correlation between Girdin expression and c-MYC expression. Moreover, we found that Girdin knockdown in c-MYC-overexpressing pancreatic cancer cells slowed cell growth, blocked the cell cycle progression, significantly promoted apoptosis, and markedly decreased the cell migration and invasion. This finding indicated that silencing Girdin could mitigate the effect of c-MYC on promoting proliferation and metastasis of pancreatic cancer. Overall, this study provided evidence that Girdin promoted pancreatic cancer development presumably by regulating the c-MYC overexpression.

IncRNA LUCAT1 acts as a Potential Biomarker and Demonstrates Malignant Biological Behaviors in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) remains the fourth-leading malignancy worldwide and has a high mortality rate. Accumulating evidence reveals that long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and metastasis and can be used as potential biomarkers for diagnosis and prognosis. METHODS: We downloaded gene expression profiles from the National Center of Biotechnology Information Gene Expression Omnibus (GEO), screened lncRNAs differentially expressed in gastric cancer tissues and adjacent tissues, and then constructed a lncRNA-miRNA-mRNA network. Seventy patients with gastric cancer were divided into two groups according to different clinical characteristics. The expression of lncRNA LUCAT1 in gastric cancer was detected by reverse transcription polymerase chain reaction (RT-PCR). The AGS and SGC-7901 cell lines were used in CCK8 assay, apoptosis, cell cycle test, transwell assay, and wound healing assay. RESULTS: The expression level of LUCAT1 was associated with tumor diameter (p < 0.001), tissue differentiation grade (p = 0.026), and LNM status (p = 0.020) in GC. The results showed that the lncRNA LUCAT1 could promote the proliferation, invasion, and migration of GC cells, inhibit the apoptosis of GC cells, and affect the process of cell cycles. CONCLUSIONS: The lncRNA LUCAT1 may be used as a potential biomarker for early signs of LNM in GC and may play a crucial role in the development of GC.

A Metal-Polymer Hybrid Biomimetic System for use in the Chemodynamic-Enhanced Photothermal Therapy of Cancers.

This article reports the fabrication of a smart biomimetic enzyme system, which incorporates a pH-responsive chemodynamic therapy (CDT) combined with a photothermal (PTT) therapy approach in resolving the high recurrence rate of deadly cancers. The resulting enzyme system comprises copper sulfide (CuS) nanoparticle (NP) cores as Fenton-like catalysts, and a photothermal-active generation 5 poly(amidoamine) (G5) dendrimer as a template for the entrapment of Cu NPs and the compression of glucose oxidase (GOD). GOD is introduced to produce H2 O2 necessary in the sequential Fenton-like reaction, and this generates hydroxyl radicals that kill the cancerous cells. Polyethylene glycol is added to the system to improve biocompatibility. Mechanism study suggests that the constructed CuS/G5-GOD-based system has a better Fenton-like catalytic activity than a Fe3 O4 -GOD-based system. This allows the further inhibition on the residual tumors from recurrence and metastasis through CDT after being treated by PTT. The developed smart nanoscale biomimetic system shows high efficiency for breast cancer suppression from recurrence and metastasis by combining PTT with a pH-responsive CDT. It has the potential to resolve the essential issue of cancer recurrence after its initial clinic treatment.

Latexin inhibits the proliferation of CD133+ miapaca-2 pancreatic cancer stem-like cells.

BACKGROUND: An increasing number of evidence suggests that pancreatic cancer contains cancer stem cells (CSCs), which may be relevant to the resistance of chemotherapy. Latexin (Lxn) is a negative regulator of stem cell proliferation and we investigate the effects of Lxn on CD133+ pancreatic cancer stem-like cells. METHODS: CD133+ miapaca-2 cells, a human pancreatic carcinoma cell line, were isolated and sorted by magnetic activated cell sorting and flow cytometry. The capacity for self-renewal, proliferation, and tumorigenicity of CD133+ miapaca-2 cells was determined by the floating spheres test and tumor xenograft assays. Protein and mRNA expression of Lxn in CD133+ and CD133- miapaca-2 cells were detected by Western blotting and qRT-PCR, respectively. After CD133+ miapaca-2 cells were treated with Lxn in serum-free medium (SFM), cell proliferation was assayed with a Cell Counting Kit 8 (CCK-8) and apoptosis was analyzed by flow cytometry. The protein and mRNA expression levels of Bcl-2, bax, and c-myc were also analyzed. RESULTS: We successfully isolated CD133+ miapaca-2 cells that exhibited the capacity for self-renewal in SFM, a proliferation potential in DMEM supplemented with FBS, and high tumorigenicity in nude mice. Lxn protein and mRNA expression levels in CD133+ miapaca-2 cells were significantly lower than those in CD133- cells. Lxn-treated CD133+ miapaca-2 cells exhibited increased apoptosis and low proliferation activity, down-regulation of Bcl-2 and c-myc expression, and up-regulation of Bax expression in a dose-dependent manner. CONCLUSIONS: Lxn induces apoptosis and inhibits the proliferation of CD133+ miapaca-2 cells. These changes are associated with down-regulation of Bcl-2 and c-myc and up-regulation of Bax.

Application and value of anxiety and depression scale in patients with functional dyspepsia.

BACKGROUND: Patients with functional dyspepsia (FD) cannot be assessed for their mental health using a suitable and practical measure. The purpose of the study is to investigate the usefulness of several anxiety and depression scales in patients with FD, offering recommendations for clinical identification and therapy. METHODS: From September 2021 to September 2022, patients were sought and selected. The psychological symptoms were assessed using ten depression or anxiety questionnaires. The receiver operating characteristic (ROC) curve, Spearman analysis, Pearson correlation analysis, and single factor analysis were applied. RESULTS: Prospective analysis was performed on 142 healthy individuals and 113 patients with FD. In the case group, anxiety and depression symptoms were more common than in the control group, and the 10 scales showed strong validity and reliability. HAMD had the strongest connection with the PHQ-9 score on the depression scale (0.83). The score correlation between SAS and HAMA on the anxiety analysis scale was the greatest at 0.77. The PHQ-9, SAS, HAMD, and HAMA measures performed exceptionally well in detecting FD with anxiety or depression symptoms (AUC = 0.72, 0.70, 0.70, 0.77, and 0.77, respectively). CONCLUSIONS: PHQ-9, SAS, HAMD, and HAMA scales have good application performance in FD patients. They can assist gastroenterologists in evaluating anxiety and depression symptoms, and provide reference and guidance for subsequent treatment.

Proton pump inhibitors enhance macropinocytosis-mediated extracellular vesicle endocytosis by inducing membrane v-ATPase assembly.

Besides participating in diverse pathological and physiological processes, extracellular vesicles (EVs) are also excellent drug-delivery vehicles. However, clinical drugs modulating EV levels are still lacking. Here, we show that proton pump inhibitors (PPIs) reduce EVs by enhancing macropinocytosis-mediated EV uptake. PPIs accelerate intestinal cell endocytosis of autocrine immunosuppressive EVs through macropinocytosis, thereby aggravating inflammatory bowel disease. PPI-induced macropinocytosis facilitates the clearance of immunosuppressive EVs from tumour cells, improving antitumor immunity. PPI-induced macropinocytosis also increases doxorubicin and antisense oligonucleotides of microRNA-155 delivery efficiency by EVs, leading to enhanced therapeutic effects of drug-loaded EVs on tumours and acute liver failure. Mechanistically, PPIs reduce cytosolic pH, promote ATP6V1A (v-ATPase subunit) disassembly from the vacuolar membrane and enhance the assembly of plasma membrane v-ATPases, thereby inducing macropinocytosis. Altogether, our results reveal a mechanism for macropinocytic regulation and PPIs as potential modulators of EV levels, thus regulating their functions.

Three-dimensional core-shell alginate microsphere for cancer hypoxia simulation in vitro.

Hypoxia is one of the major causes of cancer resistance and metastasis. Currently, it is still lack of convenient ways to simulate the in vivo hypoxic tumor microenvironment (TME) under normoxia in vitro. In this study, based on multi-polymerized alginate, we established a three-dimensional culture system with a core-shell structure (3d-ACS), which prevents oxygen diffusion to a certain extent, thereby simulating the hypoxic TME in vivo. The cell activity, hypoxia inducible factor (HIF) expression, drug resistance, and the related gene and protein changes of the gastric cancer (GC) cells were investigated in vitro and in vivo. The results demonstrated that the GC cells formed organoid-like structures in the 3d-ACS and manifested more aggressive growth and decreased drug responses. Our study provides an accessible hypoxia platform in the laboratory with moderate configuration and it may be applied in studies of the hypoxia-induced drug resistances and other preclinical fields.

PF-04449913 Inhibits Proliferation and Metastasis of Colorectal Cancer Cells by Down-regulating MMP9 Expression through the ERK/p65 Pathway.

INTRODUCTION: Colorectal cancer remains a life-threatening malignancy with increasing morbidity and mortality worldwide. Therefore, new and effective anti-colorectal cancer therapeutics are urgently needed. METHOD: In this study, we have studied the anti-tumor properties and potential mechanisms of PF-04449913. Colorectal cancer cell viability was reduced by PF-04449913 in a dose-dependent manner. The migration and invasion ability of malignant colon cells were attenuated by the drug, as demonstrated by the Transwell test. Moreover, PF-04449913 repressed the phosphorylation levels of ERK and other proteins, and the expression levels of MMP9. The anti-tumor effects of the drug in vivo were demonstrated in BALB/c-nude mice models, and PF-04449913 inhibited the malignant phenotype of colorectal cancer cells, including reduction of tumor size and promotion of apoptosis. At the molecular level, PF-04449913 induced a significant decrease in ERK and p65 protein phosphorylation levels and inhibited MMP9 protein expression. RESULTS: Both in vivo and in vitro results showed PF-04449913 to demonstrate antitumor effects, which have been proposed to be mediated through blockade of the ERK/p65 signaling pathway, and subsequent repression of MMP9 expression. CONCLUSION: Our study provides a new perspective on the potential clinical application of PF-04449913 in the treatment of colorectal cancer.

Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer.

Neoantigens play a crucial role in cancer immunotherapy. However, the effectiveness and safety of neoantigen-based immunotherapies in patients with colorectal cancer (CRC), particularly in the Chinese population, have not been well studied. This study explored the feasibility and effectiveness of neoantigens in the treatment of CRC. Whole-exome sequencing (WES) and transcriptome sequencing were used to identify somatic mutations, RNA expression, and human leukocyte antigen (HLA) alleles. Neoantigen candidates were predicted, and immunogenicity was assessed. The neoantigens TSHZ3-L523P, RARA-R83H, TP53-R248W, EYA2-V333I, and NRAS-G12D from Patient 4 (PW4); TASP1-P161L, RAP1GAP-S215R, MOSPD1-V63I, and NAV2-D1973N from Patient 10 (PW10); and HAVCR2-F39V, SEC11A-R11L, SMPDL3B-T452M, LRFN3-R118Q, and ULK1-S248L from Patient 11 (HLA-A0201+PW11) induced a heightened neoantigen-reactive T cell (NRT) response as compared with the controls in peripheral blood lymphocytes (PBLs) isolated from patients with CRC. In addition, we identified neoantigen-containing peptides SEC11A-R11L and ULK1-S248L from HLA-A0201+PW11, which more effectively elicited specific CTL responses than the corresponding native peptides in PBLs isolated from HLA-A0201+PW11 as well as in HLA-A2.1/Kb transgenic mice. Importantly, adoptive transfer of NRTs induced by vaccination with two mutant peptides could effectively inhibit tumor growth in tumor-bearing mouse models. These data indicate that neoantigen-containing peptides with high immunogenicity represent promising candidates for peptide-mediated personalized therapy.Abbreviations: CRC: colorectal cancer; DCs: dendritic cells; ELISPOT: enzyme-linked immunosorbent spot; E:T: effector:target; HLA: human leukocyte antigen; MHC: major histocompatibility complex; Mut: mutant type; NGS: next-generation sequencing; NRTs: neoantigen-reactive T cells; PBMCs: peripheral blood mononuclear cells; STR: short tandem repeat; PBLs: peripheral blood lymphocytes; PBS: phosphate-buffered saline; PD-1: programmed cell death protein 1; TILs: tumor-infiltrating lymphocytes; RNA-seq: RNA sequencing; Tg: transgenic; TMGs: tandem minigenes; WES: whole-exome sequencing; WT: wild-type.

Duodenal ulcer caused by coil wiggle after digital subtraction angiography-guided embolization: A case report.

BACKGROUND: Acute gastrointestinal bleeding (GIB) is a life-threatening medical emergency with high morbidity and mortality. Transcatheter embolization with endovascular coils under digital subtraction angiography guidance is a common and effective method for the treatment of GIB with high technical success rates. Duodenal ulcers caused by coils wiggled from the branch of the gastroduodenal artery, which is a rare complication, have not previously been reported in a patient with right intrathoracic stomach. CASE SUMMARY: A 62-year-old man had undergone thoracoscopy-assisted radical resection of esophageal cancer and gastroesophageal anastomosis 3 years ago, resulting in right intrathoracic stomach. He was admitted to the hospital 15 mo ago for dizziness and suffered acute GIB during his stay. Interventional surgery was urgently performed to embolize the branch of the gastroduodenal artery with endovascular coils. After 15 mo, the patient was re-admitted with a chief complaint of melena for 2 d, esophagogastroduodenoscopy and abdominal computed tomography revealed that some endovascular coils had migrated into the duodenal bulb, leading to a deep ulcer. Bleeding was controlled after conservative treatment. Seven months later, duodenal balloon dilatation was performed to relieve the stenosis after the removal of a few coils, and the patient was safely discharged with only one coil retained in the duodenum due to difficulties in complete removal and risk of bleeding. Mild melena recurred once during the long-term follow-up. CONCLUSION: Although rare, coil wiggle after interventional therapy requires careful attention, effective precautionary measures, and more secure alternative treatment methods.

Haemorrhagic ileal haemolymphangioma: a case report and review of the literature.

We describe herein a 37-year-old woman with a 2-week history of melena who was eventually diagnosed with ileal haemolymphangioma, a rare benign tumour. Local mucosal congestion and swelling were found through single-balloon enteroscopy, which showed an irregular protuberance approximately 10 cm long, located 3.2 m from the Treitz ligament. We performed a laparoscopic-assisted partial resection of the small intestine combined with intestinal adhesiolysis. According to postoperative pathology, the final diagnosis was ileal haemolymphangioma with haemorrhage.

A novel approach for treatment of unresectable extrahepatic bile duct carcinoma: design of radioactive stents and an experimental trial in healthy pigs.

BACKGROUND: Patients diagnosed with extrahepatic bile duct carcinoma (EBDC) have a poor prognosis. OBJECTIVE: The purpose of these studies was to design radioactive stents for EBDC and to evaluate the feasibility and safety of the stents in healthy pigs. DESIGN: Plastic stents with inserted iodine-125 seeds were designed and tested in 11 healthy pigs. The pigs were divided into 4 groups on the basis of radiation doses. INTERVENTIONS: The stents with estimated radiation dose at a 5-mm radial distance from the axis of the seeds of 30 Gy, 60 Gy, and 90 Gy were implanted in the common bile duct (CBD) in groups A, B, and C (n = 3 in each group), with the control group (n = 2) being implanted with the stents containing nonradioactive seeds. MAIN OUTCOME MEASUREMENTS: Histologic evaluation was performed under a light microscope. RESULTS: The procedures were successfully performed on all pigs. Severe hyperplasia of the mucosa was seen in the control group. In the experimental groups, obvious mucosal necrosis near the radioactive seeds was observed but without perforation of the CBD wall. In lower-dose groups (30 Gy), mild hyperplasia of mucosal glands with fibrosis under the necrosis layer was seen. However, after the increase of the dose, mucosal glands were disappearing without a visible mucosal layer. CONCLUSIONS: The radioactive stents are safe at each dose in healthy pigs. Moreover, our observations indicate the feasibility to design specific radioactive stents according to the size, shape, and position of EBDC in future clinical applications.

Therapeutic Effect of Tanshinone IIA on Liver Fibrosis and the Possible Mechanism: A Preclinical Meta-Analysis.

BACKGROUND: Liver fibrosis is a serious human health problem, and there is a need for specific antifibrosis drugs in the clinic. Tanshinone IIA has recently been reported to have a role in the treatment of liver fibrosis. However, the evidence supporting its antifibrotic effect is not sufficient, and the underlying mechanism is not clear. We thus performed this meta-analysis of animal research to assess the therapeutic effect of tanshinone IIA on liver fibrosis and analyzed the possible associated mechanism to provide a reference for further clinical drug preparation and clinical research. METHODS: We collect related articles from the databases PubMed, Web of Science, Embase, Wanfang, VIP, and CNKI. The quality of the included studies was evaluated according to the SYRCLE risk of bias tool for animal studies. Data were analyzed using RavMan 5.3 and Stata 12.0 software. RESULTS: A total of 404 articles were retrieved from the databases. After screening, 11 articles were included in the analysis. The included studies' methodological quality was generally low, and an obvious publication bias was found. The results showed that tanshinone IIA significantly improved liver function in experimental animals and reduced the level of liver fibrosis by reducing inflammation and inhibiting immunity, antiapoptotic processes, and HSC activation. CONCLUSION: Tanshinone IIA can effectively improve liver fibrosis and liver function in animal models and is worthy of future higher quality animal studies and clinical drug trials.

Overexpression of calpain­1 predicts poor outcome in patients with colorectal cancer and promotes tumor cell progression associated with downregulation of FLNA.

Several studies have demonstrated that calpain­1 is involved in a variety of pathophysiological processes, including tumorigenesis. However, the clinical relevance and role of calpain­1 in colorectal cancer (CRC) are unclear. Filamin A (FLNA) is an actin­binding protein that participates in cancer progression and can be cleaved by calpain­1. In the present study, the protein expression levels of calpain­1 and FLNA were detected by immunohistochemistry in 467 matched cancerous and paracancerous tissues from patients with CRC. The staining results and the clinicopathological characteristics of the patients were comprehensively analyzed. A high expression level of calpain­1 was strongly associated with age, metastasis, Dukes stage and survival time but not with sex, histologic grade, tumour location or tumor size. By contrast, a low expression level of FLNA was significantly associated with tumor size, histological grade, metastasis, Dukes stage and survival time, but not with age, sex, or tumor location. Kaplan­Meier survival analysis demonstrated that patients with calpain­1 overexpression had a shorter mean overall survival (OS) than patients with lower levels of calpain­1 expression. Unlike high levels of calpain­1, high levels of FLNA were associated with longer OS than lower levels of FLNA expression. Furthermore, calpain­1 expression was inversely correlated with FLNA expression. The relationship between calpain­1 and FLNA was further confirmed using CRC cell lines in vitro. When calpain­1 expression decreased in CRC cells, FLNA expression increased. Furthermore, calpain­1 knockdown in CRC cells resulted in decreased proliferation, colony formation, migration and invasion. The present findings suggest that calpain­1 overexpression predicted a poor outcome in patients with CRC and promoted tumor progression, possibly via FLNA downregulation.

Delayed endoscopic removal of sharp foreign body in the esophagus increased clinical complications: An experience from multiple centers in China.

Foreign bodies impaction in the esophagus is a common clinical emergency. The aim of this study was to investigate the clinical features of foreign body ingestion, and to analyze the risk factors of complications during the endoscopic procedure.From 18 general hospitals in Zhejiang Province in China, 595 patients who underwent gastroscopic removal of ingested foreign bodies were prospectively recruited. Patient characteristics, clinical features, foreign body features, clinical outcomes, and complications were documented.The most common types of foreign body in the esophagus were sharp objects (75.9%), including fish bones (34.0%), chicken bones (22.1%), and fruit nuclei (17.1%). The remaining types were non-sharp objects (24.1%), including food bolus (14.6%). Most objects were lodged in the proximal esophagus (75.9%). Foreign body-related complications occurred in 63 patients (10.5%), including hemorrhage (5.0%), perforation and infection (5.5%). The complication rate was increased by 4.04- and 8.48- fold when endoscopic retrieval was performed after impacted for over 24 and 48 hours, respectively, after impaction, as compared with within 12 hours. Logistic regression analysis revealed that the patients with sharp objects developed more complications than those with non-sharp ones (odds ratio, 2.85; 95% confidence interval, 1.08-7.50; P = .034). However, complications were unrelated with the location in the esophagus or length of foreign bodies (P > .05).Sharp objects were the most frequently ingested foreign bodies in the esophagus in China. The prevalence of complications was increased in the patients with long foreign body retention time (>24 hours) and sharp objects. Sharp foreign bodies in the esophagus are recommended to be removed within 24 hours.

A novel approach for treatment of unresectable pancreatic cancer: design of radioactive stents and trial studies on normal pigs.

PURPOSE: Patients diagnosed with pancreatic cancer typically have a poor prognosis. The aims of these studies were to design radioactive stents and to evaluate the feasibility and safety of the stents in animals. EXPERIMENTAL DESIGN: To combine the effects of stents and brachytherapy, plastic stents with inserted iodine-125 seeds were designed and tested in 18 normal pigs. The pigs were divided into five groups on the basis of radiation dose. The estimated radiation dose at a 5-mm radial distance from the axis of the seeds was 50 Gy in group A, 100 Gy in group B, 150 Gy in group C, and 200 Gy in group D, with four pigs in each group. In the control group (n = 2), the same plastic stents with non-radioactive seeds were implanted in the pancreatic duct. RESULTS: The procedures were successfully done on 14 of 18 (78%) pigs, whereas pancreatic duct perforation occurred in four pigs (22%). The thickened wall of the dilated pancreatic duct was clearly observed in the control group. However, the normal morphologic structure of the pancreatic duct wall disappeared in the experimental groups. Histopathologic examination revealed that the stents were surrounded with necrotic tissues and lateral fibrous tissues. During the follow-up period, the width of outside fibrous tissues gradually increased. CONCLUSIONS: These results indicate that the radioactive stents are safe in all dose groups, and it is feasible to design a special radioactive stent for each patient according to the size, shape, and position of the pancreatic tumor.