The management of postoperative upper alimentary tract fistulas: A single-center experience of endoscopic tissue glue repair and recommendations of a systematic review.

BACKGROUND/PURPOSE: The appropriate management of postoperative upper alimentary tract fistula (UATF) remains uncertain. The efficacy of esophagogastroduodenoscopy (EGD) tissue glue repair in the treatment of patients with postoperative UATF was explored. We also conducted a systematic review of the literature regarding the inpatient management of UATF. METHODS: Totally 24 patients received EGD tissue glue repair for postoperative UATF at our institute from April 2014 to April 2020. Independent characteristics of size of fistula, location of the UATF, complications, and recurrences were analyzed. PubMed and Cochrane Library databases were reviewed. A pooled analysis was performed, and subgroup analysis was conducted separately for different anatomic locations and techniques. RESULTS: With a mean follow-up of 40 months, the fistula failed to close with EGD tissue glue repair in 2 of 24 patients (8.3%). Eight patients required repeated EGD tissue glue repair, which was more frequent in oral or thoracic UATF (p = 0.053), but all achieved a successful seal in the EGD tissue after glue repair alone (n = 22). The fistula size was correlated with the demand for repeated EGD tissue glue repair (p = 0.017). Besides, a total of 30 studies regarding 2356 cases of postoperative UATF between 2010 and 2021 were retrieved and analyzed. Several non-operative methods were generally accepted as the initial approach, with a non-inferior success rate compared to operative techniques. CONCLUSION: The results suggest that no single approach toward UATF is superior in terms of success rate and healing time. The potential advantages of EGD tissue glue repair after drainage were more suitable for patients with postoperative UATF and multiple comorbidities.

Software-Based Analysis of the Taller-Than-Wide Feature of High-Risk Thyroid Nodules.

BACKGROUND: Shape is one of the most important features in the diagnosis of malignant thyroid nodules. This characteristic has been described qualitatively, but only shapes that appear markedly different can be easily differentiated at first interpretation. This study sought to clarify whether software-based shape indexes are useful for the detection of thyroid cancers. METHODS: In the final analysis, 200 participants with 231 pathologically proven nodules participated in the study. Ultrasound features were assessed by clinicians. The tumor contour was auto-defined, and shape indexes were calculated using commercial software. RESULTS: Of the 231 nodules, 134 were benign and 97 were malignant. The presence of taller-than-wide (TTW) dimensions differed significantly between the benign and malignant thyroid tumors. Designation of TTW assessed by the software had a higher kappa value and proportional agreement than TTW assessed by clinicians. Disagreement between the clinician and software in designating nodules as TTW occurred for 28 nodules. The presence of other ultrasonic characteristics and small differences in the height and width measurements were causes for the incorrect interpretation of the TTW feature. CONCLUSION: The proposed software-based quantitative analysis of tumor shape seems to be promising as an important advance compared with conventional TTW features evaluated by operators because it allows for a more reliable and consistent distinction and is less influenced by other ultrasonic features.

Differences in the ultrasonographic appearance of thyroid nodules after radiofrequency ablation.

CONTEXT: Radiofrequency ablation (RFA) is a well-tolerated approach to treating benign thyroid nodules (TNs), but no index can predict its success. Other than size decrease, little is known about TN appearance on ultrasonography (US) after RFA. OBJECTIVE: This study aimed to (a) assess the effectiveness of single-session RFA treatment, (b) determine whether pre-ablation US characteristics correlate with its effectiveness, and (c) demonstrate TN characteristics on baseline and follow-up US. DESIGN: Retrospective cohort study among the patients who underwent single-session RFA for the treatment of benign TNs at a referral medical center between January 2018 and April 2019. PATIENTS: A total of 116 patients (137 nodules) were included in the study. MEASUREMENTS: Characteristics were quantified using commercial software. TNs were classified into 2015 American Thyroid Association (ATA) sonographic patterns and American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TI-RADS) categories. RESULTS: The average volume reduction ratio (VRR) was 74.51% in 1 year (95% confidence interval, 70.63%-78.39%). The only pre-ablation US feature significantly different between nodules with VRR <50% and VRR >50% was the cyst composition (0.05 vs. 0.02, p-value = .02). The VRR and margin change in the first 3 months after ablation were found to be leading indicators significantly correlated to the VRR in 6 months with correlation coefficients (r) = .72 and -.28 (p-value < .0001 and = .0008) and VRR in 1 year with r = .65 and -.17 (p-value < .0001 and = .046), respectively. After RFA, more TNs became ATA high suspicion (2.9% vs. 19.7%, p < .0001) and more appeared to be the non-ATA patterns (12.4% vs. 23.4%, p < .0001). Also, a greater number of post-RFA TNs were classified as ACR-TI-RADS categories 4 and 5 (40.1% vs. 70.1%, p < .0001). CONCLUSIONS: Radiofrequency ablation therapy is effective for treating TNs. Pre-ablation cyst components, 3-month post-ablation volume reduction and margin change of TNs were related to the 6-month and 1-year response. Clinicians should consider that TNs would appear peculiar on US after RFA, mistakenly suggesting malignant potential.

Adjuvant tegafur-uracil (UFT) or S-1 monotherapy for advanced gastric cancer: a single center experience.

BACKGROUND: Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated. METHODS: Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups. RESULTS: From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted. CONCLUSIONS: This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.

Assessing efficacy of antiviral therapy for COVID-19 patients: A case study on remdesivir with bayesian synthesis design and multistate analysis.

BACKGROUND/PURPOSE: A synthesis design and multistate analysis is required for assessing the clinical efficacy of antiviral therapy on dynamics of multistate disease progression and in reducing the mortality and enhancing the recovery of patients with COVID-19. A case study on remdesivir was illustrated for the clinical application of such a novel design and analysis. METHODS: A Bayesian synthesis design was applied to integrating the empirical evidence on the one-arm compassion study and the two-arm ACTT-1 trial for COVID-19 patients treated with remdesivir. A multistate model was developed to model the dynamics of hospitalized COVID-19 patients from three transient states of low, medium-, and high-risk until the two outcomes of recovery and death. The outcome measures for clinical efficacy comprised high-risk state, death, and discharge. RESULTS: The efficacy of remdesivir in reducing the risk of death and enhancing the odds of recovery were estimated as 31% (95% CI, 18-44%) and 10% (95% CI, 1-18%), respectively. Remdesivir therapy for patients with low-risk state showed the efficacy in reducing subsequent progression to high-risk state and death by 26% (relative rate (RR), 0.74; 95% CI, 0.55-0.93) and 62% (RR, 0.38; 95% CI, 0.29-0.48), respectively. Less but still statistically significant efficacy in mortality reduction was noted for the medium- and high-risk patients. Remdesivir treated patients had a significantly shorter period of hospitalization (9.9 days) compared with standard care group (12.9 days). CONCLUSION: The clinical efficacy of remdesvir therapy in reducing mortality and accelerating discharge has been proved by the Bayesian synthesis design and multistate analysis.

Evaluating medical capacity for hospitalization and intensive care unit of COVID-19: A queue model approach.

BACKGROUND: The surge of COVID-19 pandemic has caused severe respiratory conditions and a large number of deaths due to the shortage of intensive care unit (ICU) in many countries. METHODS: We developed a compartment queue model to describe the process from case confirmation, home-based isolation, hospitalization, ICU, recovery, and death. By using public assessed data in Lombardy, Italy, we estimated two congestion indices for isolation wards and ICU. The excess ICU needs were estimated in Lombardy, Italy, and other countries when data were available, including France, Spain, Belgium, New York State in the USA, South Korea, and Japan. RESULTS: In Lombardy, Italy, the congestion of isolation beds had increased from 2.2 to the peak of 6.0 in March and started to decline to 3.9 as of 9th May, whereas the demand for ICU during the same period has not decreased yet with an increasing trend from 2.9 to 8.0. The results showed the unmet ICU need from the second week in March as of 9th May. The same situation was shown in France, Spain, Belgium, and New York State, USA but not for South Korea and Japan. The results with data until December 2020 for Lombardy, Italy were also estimated to reflect the demand for hospitalization and ICU after the occurrence of viral variants. CONCLUSION: Two congestion indices for isolation wards and ICU beds using open assessed tabulated data with a compartment queue model underpinning were developed to monitor the clinical capacity in hospitals in response to the COVID-19 pandemic.

Classification of community-acquired outbreaks for the global transmission of COVID-19: Machine learning and statistical model analysis.

BACKGROUND: As Coronavirus disease 2019 (COVID-19) pandemic led to the unprecedent large-scale repeated surges of epidemics worldwide since the end of 2019, data-driven analysis to look into the duration and case load of each episode of outbreak worldwide has been motivated. METHODS: Using open data repository with daily infected, recovered and death cases in the period between March 2020 and April 2021, a descriptive analysis was performed. The susceptible-exposed-infected-recovery model was used to estimate the effective productive number (Rt). The duration taken from Rt > 1 to Rt < 1 and case load were first modelled by using the compound Poisson method. Machine learning analysis using the K-means clustering method was further adopted to classify patterns of community-acquired outbreaks worldwide. RESULTS: The global estimated Rt declined after the first surge of COVID-19 pandemic but there were still two major surges of epidemics occurring in September 2020 and March 2021, respectively, and numerous episodes due to various extents of Nonpharmaceutical Interventions (NPIs). Unsupervised machine learning identified five patterns as "controlled epidemic", "mutant propagated epidemic", "propagated epidemic", "persistent epidemic" and "long persistent epidemic" with the corresponding duration and the logarithm of case load from the lowest (18.6 ± 11.7; 3.4 ± 1.8)) to the highest (258.2 ± 31.9; 11.9 ± 2.4). Countries like Taiwan outside five clusters were classified as no community-acquired outbreak. CONCLUSION: Data-driven models for the new classification of community-acquired outbreaks are useful for global surveillance of uninterrupted COVID-19 pandemic and provide a timely decision support for the distribution of vaccine and the optimal NPIs from global to local community.

Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation.

RATIONALE: Cardiac fibrosis plays a critical role in the pathogenesis of heart failure. Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited, and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics. Exploiting coexpression gene network analysis on RNA sequencing data from failing human heart, we identified TXNDC5 (thioredoxin domain containing 5), a cardiac fibroblast (CF)-enriched endoplasmic reticulum protein, as a potential novel mediator of cardiac fibrosis, and we completed experiments to test this hypothesis directly. OBJECTIVE: The objective of this study was to determine the functional role of TXNDC5 in the pathogenesis of cardiac fibrosis. METHODS AND RESULTS: RNA sequencing and Western blot analyses revealed that TXNDC5 mRNA and protein were highly upregulated in failing human left ventricles and in hypertrophied/failing mouse left ventricle. In addition, cardiac TXNDC5 mRNA expression levels were positively correlated with those of transcripts encoding transforming growth factor ß1 and ECM proteins in vivo. TXNDC5 mRNA and protein were increased in human CF (hCF) under transforming growth factor ß1 stimulation in vitro. Knockdown of TXNDC5 attenuated transforming growth factor ß1-induced hCF activation and ECM protein upregulation independent of SMAD3 (SMAD family member 3), whereas increasing expression of TXNDC5 triggered hCF activation and proliferation and increased ECM protein production. Further experiments showed that TXNDC5, a protein disulfide isomerase, facilitated ECM protein folding and that depletion of TXNDC5 led to ECM protein misfolding and degradation in CF. In addition, TXNDC5 promotes hCF activation and proliferation by enhancing c-Jun N-terminal kinase activity via increased reactive oxygen species, derived from NAD(P)H oxidase 4. Transforming growth factor ß1-induced TXNDC5 upregulation in hCF was dependent on endoplasmic reticulum stress and activating transcription factor 6-mediated transcriptional control. Targeted disruption of Txndc5 in mice (Txndc5-/-) revealed protective effects against isoproterenol-induced cardiac hypertrophy, reduced fibrosis (by ≈70%), and markedly improved left ventricle function; post-isoproterenol left ventricular ejection fraction was 59.1±1.5 versus 40.1±2.5 (P<0.001) in Txndc5-/- versus wild-type mice, respectively. CONCLUSIONS: The endoplasmic reticulum protein TXNDC5 promotes cardiac fibrosis by facilitating ECM protein folding and CF activation via redox-sensitive c-Jun N-terminal kinase signaling. Loss of TXNDC5 protects against ß agonist-induced cardiac fibrosis and contractile dysfunction. Targeting TXNDC5, therefore, could be a powerful new therapeutic approach to mitigate excessive cardiac fibrosis, thereby improving cardiac function and outcomes in patients with heart failure.

A 2-Phase Merge Filter Approach to Computer-Aided Detection of Breast Tumors on 3-Dimensional Ultrasound Imaging.

OBJECTIVES: The role of image analysis in 3-dimensional (3D) automated breast ultrasound (ABUS) images is increasingly important because of its widespread use as a screening tool in whole-breast examinations. However, reviewing a large number of images acquired from ABUS is time-consuming and sometimes error prone. The aim of this study, therefore, was to develop an efficient computer-aided detection (CADe) algorithm to assist the review process. METHODS: The proposed CADe algorithm consisted of 4 major steps. First, initial tumor candidates were formed by extracting and merging hypoechoic square cells on 2-dimensional (2D) transverse images. Second, a feature-based classifier was then constructed using 2D features to filter out nontumor candidates. Third, the remaining 2D candidates were merged longitudinally into 3D masses. Finally, a 3D feature-based classifier was used to further filter out nontumor masses to obtain the final detected masses. The proposed method was validated with 176 passes of breast images acquired by an Acuson S2000 automated breast volume scanner (Siemens Medical Solutions USA, Inc., Malvern, PA), including 44 normal passes and 132 abnormal passes containing 162 proven lesions (79 benign and 83 malignant). RESULTS: The proposed CADe system could achieve overall sensitivity of 100% and 90% with 6.71 and 5.14 false-positives (FPs) per pass, respectively. Our results also showed that the average number of FPs per normal pass (7.16) was more than the number of FPs per abnormal pass (6.56) at 100% sensitivity. CONCLUSIONS: The proposed CADe system has a great potential for becoming a good companion tool with ABUS imaging by ensuring high sensitivity with a relatively small number of FPs.

Quantitative Proteomics of Th-MYCN Transgenic Mice Reveals Aurora Kinase Inhibitor Altered Metabolic Pathways and Enhanced ACADM To Suppress Neuroblastoma Progression.

Neuroblastoma is a neural crest-derived embryonal tumor and accounts for about 15% of all cancer deaths in children. MYCN amplification is associated with aggressive and advanced stage of high-risk neuroblastoma, which remains difficult to treat and exhibits poor survival under current multimodality treatment. Here, we analyzed the transcriptomic profiles of neuroblastoma patients and showed that aurora kinases lead to poor survival and had positive correlation with MYCN amplification and high-risk disease. Further, pan-aurora kinase inhibitor (tozasertib) treatment not only induces cell-cycle arrest and suppresses cell proliferation, migration, and invasion ability in MYCN-amplified (MNA) neuroblastoma cell lines, but also inhibits tumor growth and prolongs animal survival in Th-MYCN transgenic mice. Moreover, we performed quantitative proteomics and identified 150 differentially expressed proteins after tozasertib treatment in the Th-MYCN mouse model. The functional and network-based enrichment revealed that tozasertib alters metabolic processes and identified a mitochondrial flavoenzyme in fatty acid ß-oxidation, ACADM, which is correlated with aurora kinases and neuroblastoma patient survival. Our findings indicate that the aurora kinase inhibitor could cause metabolic imbalance, possibly by disturbing carbohydrate and fatty acid metabolic pathways, and ACADM may be a potential target in MNA neuroblastoma.

B-Cell Activating Factor Enhances Hepatocyte-Driven Angiogenesis via B-Cell CLL/Lymphoma 10/Nuclear Factor-KappaB Signaling during Liver Regeneration.

B-cell activating factor (BAFF) is found to be associated with the histological severity of nonalcoholic steatohepatitis (NASH). BAFF was also found to have a protective role in hepatic steatosis via down regulating the expression of steatogenesis genes and enhancing steatosis in hepatocytes through BAFF-R. However, the roles of BAFF during liver regeneration are not well defined. In this study, C57/B6 mice with 70% partial hepatectomy were used as a liver regeneration model. BAFF expression was determined by enzyme immunoassay, and anti-BAFF-neutralizing antibodies were administered to confirm the effects of BAFF on liver regeneration. Western blotting, immunohistochemistry, and florescence staining determined the expression of B-cell CCL/lymphoma 10 (BCL10). The angiogenesis promoting capability was evaluated after the transfection of cells with siRNA targeting BCL10 expression, and the role of NF-κB was assessed. The results revealed that the BAFF and BCL10 levels were upregulated after partial hepatectomy. Treatment with anti-BAFF-neutralizing antibodies caused death in mice that were subjected to 70% partial hepatectomy within 72 h. In vitro, recombinant BAFF protein did not enhance hepatocyte proliferation; however, transfection with BCL10 siRNA arrested hepatocytes at the G2/M phase. Interestingly, conditioned medium from BAFF-treated hepatocytes enhanced angiogenesis and endothelial cell proliferation. Moreover, Matrix metalloproteinase-9 (MMP-9), Fibroblast growth factor 4 (FGF4), and Interleukin-8 (IL-8) proteins were upregulated by BAFF through BCL10/NF-κB signaling. In mice that were treated with anti-BAFF-neutralizing antibodies, the microvessel density (MVD) of the remaining liver tissues and liver regeneration were both reduced. Taken together, our study demonstrated that an increased expression of BAFF and activation of BCL10/NF-κB signaling were involved in hepatocyte-driven angiogenesis and survival during liver regeneration.

Intrapleural Epinephrine Irrigation for Massive Malignant Hemothorax.

Massive malignant hemothorax (MMH) is a rare and serious complication encountered in the field of oncology and can be life threatening. It is often difficult and complex to manage. Herein, we present cases of four patients who had MMH and in whom a hemothorax was successfully stopped via continuous intrapleural irrigation with epinephrine (5-mg epinephrine/1,000-mL normal saline, infused at 100 mL/h) instead of a conventional surgical approach. Although no patient deaths were attributed to intractable bleeding, two deaths were related to multiple organ failure. Despite the limited number of cases, this method was a convenient, effective, and inexpensive alternative to open surgical or thoracoscopic drainage for MMH.

Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment.

UNLABELLED: Leukocyte cell-derived chemotoxin 2 (LECT2) has been shown to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the underlying mechanism has not yet been completely defined. Here, we employ a LECT2-affinity column plus liquid chromatography coupled with tandem mass spectrometry to identify LECT2-binding proteins and found that MET receptor strongly interacted with LECT2 protein. Despite the presence of hepatocyte growth factor, the LECT2 binding causes an antagonistic effect to MET receptor activation through recruitment of protein tyrosine phosphatase 1B. The antagonistic effect of LECT2 on MET activation also mainly contributes to the blockage of vascular invasion and metastasis of HCC. Furthermore, serial deletions and mutations of LECT2 showed that the HxGxD motif is primarily responsible for MET receptor binding and its antagonistic effects. CONCLUSION: These findings reveal a novel, specific inhibitory function of LECT2 in HCC by the direct binding and inactivation of MET, opening a potential avenue for treating MET-related liver cancer.

Connective tissue growth factor inhibits gastric cancer peritoneal metastasis by blocking integrin α3ß1-dependent adhesion.

BACKGROUND: Connective tissue growth factor (CTGF) plays important roles in normal and pathological conditions. The aim of this study was to investigate the role of CTGF in peritoneal metastasis as well as the underlying mechanism in gastric cancer progression. METHODS: CTGF expression levels for wild-type and stable overexpression clones were determined by Western blotting and quantitative polymerase chain reaction (Q-PCR). Univariate and multivariate analyses, immunohistochemistry, and survival probability analyses were performed on gastric cancer patients. The extracellular matrix components involved in CTGF-regulated adhesion were determined. Recombinant CTGF was added to cells or coinoculated with gastric cancer cells into mice to evaluate its therapeutic potential. RESULTS: CTGF overexpression and treatment with the recombinant protein significantly inhibited cell adhesion. In vivo peritoneal metastasis demonstrated that CTGF-stable transfectants markedly decreased the number and size of tumor nodules in the mesentery. Statistical analysis of gastric cancer patient data showed that patients expressing higher CTGF levels had earlier TNM staging and a higher survival probability after the surgery. Integrin α3ß1 was the cell adhesion molecule mediating gastric cancer cell adhesion to laminin, and blocking of integrin α3ß1 prevented gastric cancer cell adhesion to recombinant CTGF. Coimmunoprecipitation results indicated that CTGF binds to integrin α3. Coinoculation of recombinant CTGF and gastric cancer cell lines in mice showed effective inhibition of peritoneal dissemination. CONCLUSIONS: Our results suggested that gastric cancer peritoneal metastasis is mediated through integrin α3ß1 binding to laminin, and CTGF effectively blocks the interaction by binding to integrin α3ß1, thus demonstrating the therapeutic potential of recombinant CTGF in gastric cancer patients.

Laparoscopic resection for large gastric gastrointestinal stromal tumor (GIST): intermediate follow-up results.

BACKGROUND: Laparoscopic wedge resection has become a widely accepted treatment for small gastrointestinal stromal tumor (GIST) of the stomach. However, its feasibility as treatment for large gastric GIST is not known. In this retrospective study, the perioperative and oncologic outcomes of laparoscopic wedge resection for gastric GIST (5-8 cm) were reviewed. METHODS: Between November 2002 and December 2012, a total of 39 patients with primary gastric GIST sized 5-8 cm underwent surgery at a tertiary care center, including 18 patients who underwent laparoscopic wedge resection of the stomach (Lap group) and 21 patients who underwent open wedge resection of the stomach (Open group). Clinicopathological parameters were reviewed and compared between the groups. RESULTS: The demographics including age, gender, and body weight were similar between groups. The operative outcomes including blood loss, hospital stay, and surgical complications were also similar, except that operative time was longer in the Lap group (146.6 ± 50.2 vs. 113.3 ± 42.9 min in the Open group, p = 0.03). There was no tumor rupture, conversion of procedures, or major surgical morbidity in either group. The overall median follow-up time was 3.6 years (1.0-11.1). Only one patient in the Lap group had liver metastasis (4 months postoperatively). This patient remains alive 5 years later under imatinib treatment. One patient in the Open group and three patients in the Lap group have died of GIST-unrelated diseases. CONCLUSIONS: Laparoscopic wedge resection of the stomach for primary gastric GIST (5-8 cm) appears to be safe and feasible, with operative and oncological outcomes comparable to those of the open method.

Calreticulin activates ß1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells.

Fucosylation regulates various pathological events in cells. We reported that different levels of CRT (calreticulin) affect the cell adhesion and metastasis of bladder cancer. However, the precise mechanism of tumour metastasis regulated by CRT remains unclear. Using a DNA array, we identified FUT1 (fucosyltransferase 1) as a gene regulated by CRT expression levels. CRT regulated cell adhesion through α1,2-linked fucosylation of ß1 integrin and this modification was catalysed by FUT1. To clarify the roles for FUT1 in bladder cancer, we transfected the human FUT1 gene into CRT-RNAi stable cell lines. FUT1 overexpression in CRT-RNAi cells resulted in increased levels of ß1 integrin fucosylation and rescued cell adhesion to type-I collagen. Treatment with UEA-1 (Ulex europaeus agglutinin-1), a lectin that recognizes FUT1-modified glycosylation structures, did not affect cell adhesion. In contrast, a FUT1-specific fucosidase diminished the activation of ß1 integrin. These results indicated that α1,2-fucosylation of ß1 integrin was not involved in integrin-collagen interaction, but promoted ß1 integrin activation. Moreover, we demonstrated that CRT regulated FUT1 mRNA degradation at the 3'-UTR. In conclusion, the results of the present study suggest that CRT stabilized FUT1 mRNA, thereby leading to an increase in fucosylation of ß1 integrin. Furthermore, increased fucosylation levels activate ß1 integrin, rather than directly modifying the integrin-binding sites.

Clinical performance of ultrasonic backscatter parametric and nonparametric statistics in detecting early hepatic steatosis.

Diagnosis of early hepatic steatosis would allow timely intervention. B-mode ultrasound imaging was in question for detecting early steatosis, especially with a variety of concomitant parenchymal disease. This study aimed to use the surgical specimen as a reference standard to elucidate the clinical performance of ultrasonic echogenicity and backscatter parametric and nonparametric statistics in real-world scenarios. Ultrasound radio-frequency (RF) signals of right liver lobe and patient data were collected preoperatively. Surgical specimen was then used to histologically determine staging of steatosis. A backscatter nonparametric statistic (h), a known backscatter parametric statistic, i.e., the Nakagami parameter (m), and a quantitative echo intensity (env) were calculated. Among the 236 patients included in the study, 93 were grade 0 (<5% fat) and 143 were with steatosis. All the env, m and h statistics had shown significant discriminatory power of steatosis grades (AUC = 0.643-0.907 with p-value < 0.001). Mann-Whitney U tests, however, revealed that only the backscatter statistics m and h were significantly different between the groups of grades 0 and 1 steatosis. The two-way ANOVA showed a significant confounding effect of the elevated ALT on env (p-value = 0.028), but no effect on m or h. Additionally, the severe fibrosis was found to be a significant covariate for m and h. Ultrasonic signals acquired from different scanners were found linearly comparable.

A gasless laparoscopic technique of wide excision for gastric gastrointestinal stromal tumor versus open method.

BACKGROUND: Traditional open surgery for gastrointestinal stromal tumors (GIST) requires a long incision. Moreover, the gas-filling laparoscopic technique used in GIST surgery still has its limitations. Therefore, we developed a gasless laparoscopic (GL) surgery for GIST and compared it with traditional open surgery. METHODS: Between October 2007 and September 2009, 62 GIST patients in the National Taiwan University Hospital received wide excisions. Of these 62 patients, 30 underwent the new procedure (GL group) and 32 had open surgery (OS group). Preoperative and postoperative clinicopathologic characteristics were compared between the groups. RESULTS: There were no significant differences in preoperative characteristics or blood loss. However, the days to first flatus, postoperative hospital stay, wound length, white blood cell count at postoperative day one, and peak daily body temperature were all significantly improved in the GL group. Usage of postoperative analgesia on postoperative days one to five was also significantly lower in the GL group. CONCLUSIONS: Wide-excision laparoscopy for gastric GIST can be performed more safely, more effectively, and with faster postoperative recovery using the gasless technique as compared with the open method. We, therefore, recommend this new surgical technique, which hybridizes the advantages of both the traditional open method and pure laparoscopic surgery.

Laparoscopic resection for submucosal tumors near the esophagogastric junction: feasibility and short-term outcome.

BACKGROUND: Minimally invasive surgery has proved to be effective and efficient in the management of gastric submucosal tumors (SMT). However, confronting a SMT near the esophagogastric junction (EGJ) is still challenging because of the potentially devastating risks of stenosis or leakage. This study evaluated the safety, feasibility, and oncological efficacy of laparoscopic resection for SMTs located near the EGJ. METHODS: From December 2008 to November 2011, we enrolled a total of 19 patients diagnosed with gastric SMTs located near the EGJ who underwent laparoscopic surgery. The clinicopathological characteristics and surgical outcomes of the 19 patients were recorded and reviewed retrospectively. RESULTS: All 19 patients underwent laparoscopic resections of their gastric SMTs without complications during the study period. There were 9 men and 10 women, with a mean age of 63.3 ± 15.1 years (range 33-86 years). The operative duration was 187.8 ± 58.9 minutes (range 90-310 minutes). Intraoperative localization included endoscopy (n = 3), tattooing (n = 2), and combined modalities (n = 1). The exogastric (n = 12) and transgastric methods (n = 7) were used. The histopathology showed 10 gastrointestinal stromal tumors, 7 leiomyomas, 1 hyperplastic polyp, and 1 lipoma. The postoperative courses for all cases were uneventful. The mean follow-up period was 16.7 ± 9.4 months, with no recurrence noted. CONCLUSIONS: Laparoscopic resections for gastric SMTs near the EGJ are safe and feasible, with satisfactory oncological outcomes in the short term.

Changes in tumor growth and metastatic capacities of J82 human bladder cancer cells suppressed by down-regulation of calreticulin expression.

Bladder cancer is a common urothelial cancer. Through proteomic approaches, calreticulin (CRT) was identified and proposed as a urinary marker for bladder cancer. CRT is a multifunctional molecular chaperone that regulates various cellular functions such as Ca(2+) homeostasis and cell adhesion. CRT is overexpressed in various cancers, but its mechanism of action in the development of bladder tumors remains unclear. We generated J82 bladder cancer cells lines that either stably overexpressed or knocked down CRT to investigate the physiological effects of CRT on bladder tumors. Compared with the transfected control vector cells, the knockdown of CRT suppressed cell proliferation, migration, and attachment, whereas overexpression of CRT enhanced cell migration and attachment. We further demonstrated that the phosphorylation status of focal adhesion kinase and paxillin, important regulators of the focal adhesion complex, was also regulated in these cells. In contrast, phosphorylation of Src, a protein tyrosine kinase reported to be affected by CRT, was not significantly different between the control and CRT-RNAi groups. Most importantly, we observed that tumors derived from J82 CRT-RNAi cells were significantly smaller and had fewer metastatic sites in the lung and liver in vivo than did transfected control vector cells. In conclusion, our results suggest that alteration of CRT expression levels might affect bladder cancer progression in vitro and in vivo.