Interaction of Colorectal Neoplasm Risk Factors and Association with Metabolic Health Status Focusing on Normal Waist-to-Hip Ratio in Adults.

BACKGROUND: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. METHODS: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. RESULTS: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. CONCLUSIONS: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS.

Intestinal Ultrasound in Inflammatory Bowel Disease: A Novel and Increasingly Important Tool.

New and efficacious medical therapies have become available that have greatly enhanced clinicians' ability to manage inflammatory bowel diseases (IBDs). IBD activity should be assessed regularly in scheduled examinations as the part of a treat-to-target strategy for IBD care. The gold-standard approach to investigating IBD is colonoscopy, but this is an invasive procedure. Intestinal ultrasound (IUS) has played a crucial role in recent years regarding the assessment of IBD activity because it is noninvasive, safe, reproducible, and inexpensive. IUS findings could inform changes in therapeutic interventions for IBDs; this would necessitate fewer endoscopies and enable faster decision-making processes. Furthermore, patients are accepting and tolerant of IUS examinations. This review outlines the current evidence and gives indication regarding the use of IUS in the management of IBDs.

Characterization of Mammary Tumors Arising from MMTV-PyVT Transgenic Mice.

Among genetically engineered mouse models of breast cancer, MMTV-PyVT is a mouse strain in which the oncogenic polyoma virus middle T antigen is driven by the mouse mammary tumor virus promoter. The aim of the present study was to perform morphologic and genetic analyses of mammary tumors arising from MMTV-PyVT mice. To this end, mammary tumors were obtained at 6, 9, 12, and 16 weeks of age for histology and whole-mount analyses. We conducted whole-exome sequencing to identify constitutional and tumor-specific mutations, and genetic variants were identified using the GRCm38/mm10 mouse reference genome. Using hematoxylin and eosin analysis and whole-mount carmine alum staining, we demonstrated the progressive proliferation and invasion of mammary tumors. Frameshift insertions/deletions (indels) were noted in the Muc4. Mammary tumors showed small indels and nonsynonymous single-nucleotide variants but no somatic structural alterations or copy number variations. In summary, we validated MMTV-PyVT transgenic mice as a multistage model for mammary carcinoma development and progression. Our characterization may be used as a reference for guidance in future research.

Aberrant Expression of Solute Carrier Family 35 Member A2 Correlates With Tumor Progression in Breast Cancer.

BACKGROUND/AIM: A recent study suggested that solute carrier family 35 member A2 (SLC35A2) is related to poor prognosis in patients with breast cancer. SLC35A2 transports uridine diphosphate-galactose from the cytosol to the lumen of the endoplasmic reticulum and Golgi. MATERIALS AND METHODS: Immunohistochemical expression of SLC35A2 was evaluated using tissue microarrays. Cell growth, migration, and invasion of breast cancer cells were examined following loss- and gain-of-expression of SLC35A2. RESULTS: Normal breast tissue exhibited SLC35A2 immunoreactivity in the nucleus. A progressive increase in cytoplasmic expression from in situ carcinoma to invasive carcinoma was observed. There was a correlation between cytoplasmic SLC35A2 expression and breast cancer stage (p<0.001). MDA-MB-468 and MCF-7 cells transfected with SLC35A2 shRNA had unchanged cell viability but significantly reduced cell migration and invasion. In contrast, MDA-MB-231 and HCC1806 cells transfected with the SLC35A2 expression vector showed increased migration. CONCLUSION: Breast cancer progression is accompanied by differential expression patterns of SLC35A2. The migratory or invasive capacity of breast cancer cells is associated with SLC35A2 expression.

Radiomics-based nomogram as predictive model for prognosis of hepatocellular carcinoma with portal vein tumor thrombosis receiving radiotherapy.

Background: This study aims to establish and validate a predictive model based on radiomics features, clinical features, and radiation therapy (RT) dosimetric parameters for overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with RT for portal vein tumor thrombosis (PVTT). Methods: We retrospectively reviewed 131 patients. Patients were randomly divided into the training (n = 105) and validation (n = 26) cohorts. The clinical target volume was contoured on pre-RT computed tomography images and 48 textural features were extracted. The least absolute shrinkage and selection operator regression was used to determine the radiomics score (rad-score). A nomogram based on rad-score, clinical features, and dosimetric parameters was developed using the results of multivariate regression analysis. The predictive nomogram was evaluated using Harrell's concordance index (C-index), area under the curve (AUC), and calibration curve. Results: Two radiomics features were extracted to calculate the rad-score for the prediction of OS. The radiomics-based nomogram had better performance than the clinical nomogram for the prediction of OS, with a C-index of 0.73 (95% CI, 0.67-0.79) and an AUC of 0.71 (95% CI, 0.62-0.79). The predictive accuracy was assessed by a calibration curve. Conclusion: The radiomics-based predictive model significantly improved OS prediction in HCC patients treated with RT for PVTT.

Predicting Factors for Pancreatic Malignancy with Computed Tomography and Endoscopic Ultrasonography in Chronic Pancreatitis.

Diagnosing pancreatic malignancy is challenging, especially in patients with chronic pancreatitis (CP). Endoscopic ultrasonography (EUS) is a promising diagnostic procedure for discriminating between malignancy and CP. We aimed to investigate the predictive factors and reliability of computed tomography (CT) and EUS for differentiating pancreatic mass lesions and the diagnostic accuracy of EUS-FNA or FNB in patients with CP. Forty patients with CP, receiving CT and EUS-FNA or FNB for pancreatic mass lesion evaluation, were enrolled in the study. Patients' data, CT and EUS characteristics, image-based diagnosis, cytopathology, and final diagnosis were recorded. EUS was superior to CT in terms of diagnostic accuracy (92.5% vs. 82.5%, p = 0.02). Both CT and EUS showed significant predictive factors (all p < 0.05) with the tumor image hypoattenuation pattern or vessel invasion on CT and pancreatic duct dilatation, or distal pancreatic atrophy on EUS. EUS imaging is a reliable modality for evaluating pancreatic lesions, even with a CP background. The EUS image has a higher diagnostic accuracy than CT. Predicting factors, including hypoechoic pattern, pancreatic duct dilatation, and distal pancreas atrophy, may help to differentiate benign or malignant in patients with CP.

Is contrast-enhanced endoscopic ultrasound-guided fine needle biopsy better than conventional fine needle biopsy? A retrospective study in a medical center.

BACKGROUND: Contrast-enhanced endoscopic ultrasound-guided fine needle aspiration (CE-EUS-FNA) could help clinicians to precisely locate and puncture lesions, but its effect on the diagnostic yield improvement is controversial. We designed this study to observe the additional benefit of using contrast in EUS-guided tissue sampling while performing fine needle biopsy (FNB) instead of FNA, as FNB results in a higher diagnostic accuracy. METHOD: Patients who underwent EUS-FNB performed by a single medical team from January 2019 to March 2021 were included in this study. We analyzed the cytopathological diagnostic accuracy rate and number of needle passes between groups who underwent FNB with and without contrast. RESULT: We divided 133 patients who were diagnosed with a malignancy into two groups according to whether they underwent CE-EUS-FNB (n = 48) or conventional EUS-FNB (n = 85). The CE-EUS-FNB group had an equal diagnostic accuracy rate with fewer needle passes compared with the conventional EUS-FNB group. There was no significant trend change in the success cytopathological diagnostic rate for experienced endoscopists for EUS-FNA. CONCLUSION: CE-EUS-FNB had fewer needle passes but no additional benefit for diagnostic yield improvement. There was no difficult threshold for CE-EUS-FNB for endoscopists who were well trained in conventional FNA.

Effects of Helicobacter pylori infection in gastrointestinal tract malignant diseases: From the oral cavity to rectum.

Helicobacter pylori (H. pylori) has infected approximately fifty percent of humans for a long period of time. However, improvements in the public health environment have led to a decreased chance of H. pylori infection. However, a high infection rate is noted in populations with a high incidence rate of gastric cancer (GC). The worldwide fraction of GC attributable to H. pylori is greater than 85%, and a high H. pylori prevalence is noted in gastric mucosa-associated lymphoid tissue lymphoma patients. These results indicate that the majority of GC cases can be prevented if H. pylori infection is eliminated. Because H. pylori exhibits oral-oral or fecal-oral transmission, the relationship between this microorganism and other digestive tract malignant diseases has also attracted attention. This review article provides an overview of H. pylori and the condition of the whole gastrointestinal tract environment to further understand the correlation between the pathogen and the host, thus allowing improved realization of disease presentation.

Clinical efficacy and safety of peroral endoscopic myotomy for esophageal achalasia: A multicenter study in Taiwan.

BACKGROUND/OBJECTIVE: Peroral endoscopic myotomy (POEM), a novel minimally invasive treatment for esophageal achalasia, is becoming more popular globally because of its efficacy and safety. We aimed to clarify the technical concerns, efficacy, and safety of POEM for treating esophageal achalasia in Taiwan. METHODS: We conducted a retrospective study on consecutive patients with achalasia who underwent POEM between October 2016 and May 2021 at three medical centers in Taiwan. All patients underwent a comprehensive work-up before POEM, including symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram (TBE), and high-resolution impedance manometry (HRIM), and were re-evaluated three months after POEM. We compared procedure variables, adverse events, and clinical responses, including Eckardt score ≤3 and TBE and HRIM findings. RESULTS: We analyzed 92 patients in total (54 men; mean age 49.5 years [range: 20-87]; type I/II/III/unclassified: 24/51/1/16). The mean POEM procedure duration was 89.5 ± 38.2 min, though it was significantly longer in patients with prior treatment or sigmoid-type achalasia. In total, 91 patients (98.9%) showed immediate technical success, and the overall clinical success rate at three months after POEM was 95.7%. Nearly 60% of patients experienced adverse events during POEM, but most of these were mild and none required further endoscopic or surgical intervention. During a follow-up period of up to five years (median 25 months), only four patients (4.3%) showed symptomatic recurrence, but none required further treatment. CONCLUSION: POEM is a very effective and safe treatment for Taiwanese patients with achalasia, irrespective of their achalasia subtype or prior treatment failure.

Helicobacter pylori infection and increased diabetes prevalence were the risks of colorectal adenoma for adults: A systematic review and meta-analysis (PRISMA-compliant article).

BACKGROUND: Helicobacter pylori infection and hyperglycemia are associated with an increased risk of colorectal neoplasm, and may have a synergistic effect in combination. However, these 2 factors that affect colorectal neoplasm remain controversial. We aimed to carry out a meta-analysis to evaluate the study population diabetes prevalence rate and H pylori infection rate with colorectal adenoma risk for adults. METHODS: We conducted systemic research through English databases for medical reports. We also recorded the diabetes prevalence and H pylori infection prevalence in each study. We classified these studies into 4 subgroups as their background population diabetes prevalence <6% (Group 1); between 6% and 8% (Group 2); between 8% and 10% (Group 3), and more than 10% (Group 4). The random-effects model had used to calculate pooled prevalence estimates with 95% confidence interval (CI). RESULTS: Twenty-seven studies were finally eligible for meta-analysis. The random-effects model of the meta-analysis was chosen, showing pooled odds ratio (OR) equal to 1.51 (95% CI 1.39-1.63). The subgroup meta-analyses showed in Group 1 the H pylori infection associated colorectal adenoma risk OR was 1.24 (95% CI 0.86-1.78). As the diabetes rate exceed 6%, the H pylori infection became the more significant increased risk of colorectal adenoma (Group 2: OR 2.16 (95% CI 1.61-2.91); Group 3: OR 1.40 (95% CI 1.24-1.57); and Group 4: OR 1.52 (95% CI 1.46-1.57)). CONCLUSIONS: The results of this meta-analysis showed elevated diabetes prevalence combined H pylori infection increasing the risks of colorectal adenoma in the adult population.

Combination of Mesenchymal Stem Cell-Delivered Oncolytic Virus with Prodrug Activation Increases Efficacy and Safety of Colorectal Cancer Therapy.

Although oncolytic viruses are currently being evaluated for cancer treatment in clinical trials, systemic administration is hindered by many factors that prevent them from reaching the tumor cells. When administered systemically, mesenchymal stem cells (MSCs) target tumors, and therefore constitute good cell carriers for oncolytic viruses. MSCs were primed with trichostatin A under hypoxia, which upregulated the expression of CXCR4, a chemokine receptor involved in tumor tropism, and coxsackievirus and adenovirus receptor that plays an important role in adenoviral infection. After priming, MSCs were loaded with conditionally replicative adenovirus that exhibits limited proliferation in cells with a functional p53 pathway and encodes Escherichia coli nitroreductase (NTR) enzymes (CRAdNTR) for targeting tumor cells. Primed MSCs increased tumor tropism and susceptibility to adenoviral infection, and successfully protected CRAdNTR from neutralization by anti-adenovirus antibodies both in vitro and in vivo, and specifically targeted p53-deficient colorectal tumors when infused intravenously. Analyses of deproteinized tissues by UPLC-MS/QTOF revealed that these MSCs converted the co-administered prodrug CB1954 into cytotoxic metabolites, such as 4-hydroxylamine and 2-amine, inducing oncolysis and tumor growth inhibition without being toxic for the host vital organs. This study shows that the combination of oncolytic viruses delivered by MSCs with the activation of prodrugs is a new cancer treatment strategy that provides a new approach for the development of oncolytic viral therapy for various cancers.

Trilostane, a 3ß-hydroxysteroid dehydrogenase inhibitor, suppresses growth of hepatocellular carcinoma and enhances anti-cancer effects of sorafenib.

Background Human 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) is an enzyme associated with steroidogenesis, however its' role in hepatocellular carcinoma (HCC) biology is unknown. Trilostane is an inhibitor of HSD3B1 and has been tested as a treatment for patients with breast cancer but has not been studied in patients with HCC. Methods and Results The expression of HSD3B1 in HCC tumors in 57 patients were examined. A total of 44 out of 57 tumors (77.2%) showed increased HSD3B1 expression. The increased HSD3B1 in tumors was significantly associated with advanced HCC. In vitro, the knockdown of HSD3B1 expression in Mahlavu HCC cells by a short hairpin RNA (shRNA) led to significant decreases in colony formation and cell migration. The suppression of clonogenicity in the HSD3B1-knockdown HCC cells was reversed by testosterone and 17ß-estradiol. Trilostane-mediated inhibition of HSD3B1 in different HCC cells also caused significant inhibition of clonogenicity and cell migration. In subcutaneous HCC Mahlavu xenografts, trilostane (30 or 60 mg/kg, intraperitoneal injection) significantly inhibited tumor growth in a dose-dependent manner. Furthermore, the combination of trilostane and sorafenib significantly enhanced the inhibition of clonogenicity and xenograft growth, surpassing the effects of each drug used alone, with no documented additional toxicity to animals. HSD3B1 blockade was found to suppress the phosphorylation of extracellular signal-regulated kinase (ERK). The decreased ERK phosphorylation was reversed by testosterone or 17b-estradiol. Conclusions Trilostane significantly inhibited the growth of HCC by inhibiting HSD3B1 function and augmenting the efficacy of sorafenib.

Enhanced expression of coxsackievirus and adenovirus receptor in lipopolysaccharide-induced inflammatory macrophages is through TRIF-dependent innate immunity pathway.

AIMS: Inflammatory macrophages have been proposed as a therapeutic target for joint disorders caused by inflammation. This study aimed to investigate the expression and regulation of coxsackievirus-adenovirus receptor (CAR) in lipopolysaccharide (LPS)-stimulated inflammatory macrophages whereby to evaluate the feasibility of virus-directed enzyme prodrug therapy (VDEPT). MAIN METHODS: Macrophage cell lines (RAW264.7 and J774A.1) and primary macrophage cells derived from rat spleen were used to evaluate the expression of CAR protein or CAR mRNA. Specific inhibitors for TLR4 pathway were used to investigate the regulation of CAR expression. CAR expression in rat joints was documented by immunohistochemistry. Conditionally replicating adenovirus, CRAd-EGFP(PS1217L) or CRAd-NTR(PS1217H6), and non-replicating adenovirus CTL102 were used to transduce genes for enhanced green fluorescent protein (EGFP) or nitroreductase (NTR), respectively. The expression of EGFP, NTR, and the toxicity induced by CB1954 activation were evaluated. KEY FINDINGS: The in vitro experiments revealed that CAR upregulation was mediated through the TLR4/TRIF/IRF3 pathway in LPS-stimulated inflammatory macrophage RAW264.7 and J774A.1 cells. The inflammatory RAW264.7 cells upregulated CAR expression following LPS stimulation, leading to higher infectability, increased NTR expression, and enhanced sensitization to CB1954. In animal experiments, the induction of CAR expression was observed in the CD68-expressing primary macrophages and in the CD68-expressing macrophages within joints following LPS stimulation. SIGNIFICANCE: In conclusion, we report an enhanced CAR expression in inflammatory macrophages in vitro and in vivo through the immune response elicited by LPS. Thus, the TLR4/TRIF/IRF3 pathway of macrophages, when activated, could facilitate the therapeutic application of adenovirus-mediated VDEPT.

Relationship between serum gamma-glutamyl transferase level and colorectal adenoma.

BACKGROUND AND AIMS: Cost-effective serology tests may increase the predictive accuracy of colonoscopy for colorectal cancer screening. Reportedly, gamma-glutamyl transferase (GGT) is associated with oxidative stress and carcinogenesis and has been found to be elevated in the serum of cancer patients and colorectal adenoma tissue. We aimed to investigate the association between serum GGT levels and colorectal adenoma. METHODS: This single-center, health examination-based cohort enrolled 2475 subjects from 2006 to 2015. Baseline characteristics, laboratory data, bidirectional gastrointestinal endoscopy, and transabdominal ultrasonography were used to evaluate the severity of fatty liver. RESULTS: We found an elevated median GGT level in subjects with tubular adenoma compared with those without (23 IU/L and 20 IU/L, p<0.001). A GGT cutoff of ≥20 IU/L reached a maximal Youden index in receiver operating curve (ROC) analyses. Subsequent regression analyses showed an odds ratio of 1.46 (95% CI 1.17-1.82, p<0.001) for age, body mass index, diabetes diagnosis, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and positive Helicobacter pylori urease test, all being associated with an increased incidence of colon adenoma. Subgroup analysis showed that the odds ratio (OR 1.27, 95% CI 1.15-1.68, p<0.001) is only significant and highest in patients with a negative or mild fatty liver and an ALT level of ≤40 IU/L. CONCLUSIONS: The results suggested a positive correlation of GGT with colon adenoma incidence and a predictive value with a cutoff point of >20 IU/L, which is within the normal range. The effect may be most prominent for those without steatohepatitis.

Efficacy of telbivudine and entecavir against virus reactivation in HBeAg-patients undergoing chemotherapy.

The renal protective effect of telbivudine (LdT) was verified by a previous meta-analysis. It was left unclear, however if this effect offsets the associated risk of virological breakthrough in hepatitis B e-antigen-negative (HBeAg-) patients receiving chemotherapy (C/T).Records of 260 HBeAg-, non-cirrhotic cancer patients undergoing systemic C/T with prophylactic LdT or entecavir (ETV) were retrospectively investigated. The investigation was conducted 6 months after completion of C/T, patient death from cancer, or antiviral modification. Treatment duration, outcome, change of renal function, and reason for antiviral modification were analyzed. The primary endpoint was the occurrence of virological breakthrough during prophylaxis C/T and the change in renal function.Of the 126 HBeAg- patients treated with LdT, 3 (2.38%) experienced HBV virological breakthroughs, whereas none of the patients treated with ETV (P = .07) did. The estimated glomerular filtration rate for the patients treated with LdT was essentially unaltered, decreasing only slightly from 87.5 ±â€Š23.1 to 87.3 ±â€Š21.3 ml/minute/1.73 m (P = .55), while the rate for the ETV-treated patients was significantly lowered from 95.7 ±â€Š32.2 to 85.5 ±â€Š85.7 ml/minute/1.73 m (P = .0009).The absolute risk reduction ARR is 27.8% - 21.2% = 6.6%, comparing ETV with LdT for reduction of renal function impairment and the absolute risk increase for virological breakthrough during C/T, the absolute risk increase (ARI) is 2.38% - 0% = 2.38%. The overall likelihood of being helped over being harmed was 2.77. With careful selection of patients with the criteria of HBeAg-status and non-hematologic cancer, it is feasible that telbivudine raise lower probability of virological breakthroughs during prophylaxis treatment.

Impact of direct-acting antiviral therapy for hepatitis C-related hepatocellular carcinoma.

With the introduction of direct-acting antiviral (DAA) agents, hepatitis C virus (HCV) treatment has dramatically improved. However, there are insufficient data on the benefits of DAA therapy in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the outcome of patients who received DAA therapy after HCC treatment. We retrospectively reviewed patients with HCV-related HCC in a single medical center, and the outcome of patients with or without DAA therapy was analyzed. In total, 107 HCC patients were enrolled, of whom 60 had received DAA therapy after treatment for HCC. There were no significant intergroup differences in age, sex, laboratory results, or tumor burden. A more advanced stage was noted in the no DAA group (P = 0.003). In the treatment modality, sorafenib was commonly prescribed in the no DAA group (P = 0.007). The DAA group had a longer overall survival (OS) time than the no DAA group (P<0.001). When stratified by Barcelona Clinic Liver Cancer staging, the DAA group had better OS in the HCC stages 0-A and B-C (P = 0.034 and P = 0.006). There were 35 patients who received DAA therapy after curative HCC therapy. At a median follow-up of 20 months, 37.1% patients had HCC recurrence after DAA therapy. There was no statistical difference in recurrence-free survival between patients receiving and those not receiving DAA (P = 0.278). DAA therapy improved the survival outcome of HCC patients and did not increase recurrent HCC after curative therapy. .

Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer.

FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.

Endoscopic management of strictures in patients with Crohn's disease - A multi-center experience in Taiwan.

BACKGROUND/PURPOSE: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) disorder that causes relapsing inflammation and severe mucosal damage in the intestine. Crohn's disease (CD)-related stricturing complications are a major cause of surgery, disability, and reduced quality of life. Endoscopic balloon dilation (EBD) has been shown to reliably delay or prevent surgery in patients with stricturing CD. However, cases of EBD performed for stricture in CD in Taiwan are rare. In this study, we want to evaluate the experiences regarding EBD for stricturing CD in Taiwan. METHODS: We conducted a retrospective analysis of 9 medical centers in Taiwan. Patients with CD-related strictures who were treated with EBD were included and analyzed. RESULTS: In nine medical centers, a total of 26 CD patients (19 male, 7 female, mean disease duration 75.4 ± 65.2 months) underwent 42 EBD procedures during the study period. Among the subjects, an 83.3% (35/42) EBD success rate was seen, but 26.9% (7/26) patients underwent surgery after ineffective EBD. In the surgery group, the the small bowel strictures was high compared with the non-surgery group (p = 0.01). There were no significant differences in disease phenotype, disease duration or history of fistulizing disease. In the surgery group, immunosuppressant use was high, and 5-aminosalicylic acid (5-ASA) use was low compared with the non-surgery group. After EBD, the physicians tended to change the drugs, especially increasing the use of biologic agents. CONCLUSION: EBD is a safe and effective procedure for CD-related stricture, with a 83.3% success rate in Taiwan.

Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation.

Perturbed Nicotinamide adenine dinucleotide (NAD+) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT) is the rate-limiting enzyme in the kynurenine pathway participating in NAD+ generation. In this study, we demonstrated that QPRT expression was upregulated in invasive breast cancer and spontaneous mammary tumors from MMTV-PyVT transgenic mice. Knockdown of QPRT expression inhibited breast cancer cell migration and invasion. Consistently, ectopic expression of QPRT promoted cell migration and invasion in breast cancer cells. Treatment with QPRT inhibitor (phthalic acid) or P2Y11 antagonist (NF340) could reverse the QPRT-induced invasiveness and phosphorylation of myosin light chain. Similar reversibility could be observed following treatment with Rho inhibitor (Y16), ROCK inhibitor (Y27632), PLC inhibitor (U73122), or MLCK inhibitor (ML7). Altogether, these results indicate that QPRT enhanced breast cancer invasiveness probably through purinergic signaling and might be a potential prognostic indicator and therapeutic target in breast cancer.