Predictive value of FCGBP expression for treatment response and survival in rectal cancer patients undergoing chemoradiotherapy.

Despite neoadjuvant chemoradiotherapy (CRT) being the established standard for treating advanced rectal cancer, clinical outcomes remain suboptimal, necessitating the identification of predictive biomarkers for improved treatment decisions. Previous studies have hinted at the oncogenic properties of the Fc fragment of IgG binding protein (FCGBP) in various cancers; however, its clinical significance in rectal cancer remains unclear. In this study, we first conducted an analysis of a public transcriptome comprising 46 rectal cancer patients. Focusing on cell adhesion during data mining, we identified FCGBP as the most upregulated gene associated with CRT resistance. Subsequently, we assessed FCGBP immunointensity using immunohistochemical staining on 343 rectal cancer tissue blocks. Elevated FCGBP immunointensity correlated with lymph node involvement before treatment (p = 0.001), tumor invasion, and lymph node involvement after treatment (both p < 0.001), vascular invasion (p = 0.001), perineural invasion (p = 0.041), and reduced tumor regression (p < 0.001). Univariate analysis revealed a significant association between high FCGBP immunoexpression and inferior disease-specific survival, local recurrence-free survival, and metastasis-free survival (all p ≤ 0.0002). Furthermore, high FCGBP immunoexpression independently emerged as an unfavorable prognostic factor for all three survival outcomes in the multivariate analysis (all p ≤ 0.025). Enriched pathway analysis substantiated the role of FCGBP in conferring resistance to radiation. In summary, our findings suggest that elevated FCGBP immunoexpression in rectal cancer significantly correlates with a poor response to CRT and diminished patient survival. FCGBP holds promise as a valuable prognostic biomarker for rectal cancer patients undergoing CRT.

Relationship Between Rectal Swab and Tissue Samples in Mucosa-associated Microbiota in Patients With Inflammatory Bowel Disease.

BACKGROUND: Gut mucosa-associated microbiota is more closely correlated with disease phenotypes than fecal microbiota; however sampling via tissue biopsy is more invasive and uncomfortable. Rectal swab may be a suitable substitute for tissue biopsy, but its effectiveness is controversial. This study aimed to evaluate differences in the microbiota at these sites in patients with inflammatory bowel disease (IBD). METHODS: Inflammatory bowel disease patients and a control group were enrolled when surveillance colonoscopy was scheduled. Samples of colon biopsy tissues, rectal swabs during colonoscopy, and feces before bowel preparation were collected to analyze microbial composition. To explore the short-term effects of bowel preparation on swab microbiota, prepreparation swab samples were also collected from 27 IBD patients. RESULTS: A total of 33 Crohn's disease, 54 ulcerative colitis, and 21 non-IBD patients were enrolled. In beta diversity analysis, fecal microbiota clearly differed from swab and tissue microbiota in the 3 disease groups. The swab microbiota was closer to, but still different from, the tissue microbiota. Consistently, we identified that swab samples differed more in abundant genera from feces than from tissue. Beta diversity analysis did not reveal a difference in swab microbiota before and after bowel preparation, but the genus composition of most individuals varied markedly. CONCLUSIONS: Swab microbiota more closely resembled tissue microbiota relative to fecal microbiota, but there were still differences. Bowel preparation did not alter the overall swab microbiota in the short term but markedly changed the microbial composition in most patients.

Phlegmonous gastritis after biloma drainage: A case report and review of the literature.

BACKGROUND: Phlegmonous gastritis (PG) is a rare bacterial infection of the gastric submucosa and is related to septicemia, direct gastric mucosal injury, or the direct influence of infection or inflammation in neighboring organs. Here, we present a patient who had spontaneous biloma caused by choledocholithiasis and then PG resulting from bile leakage after biloma drainage. CASE SUMMARY: A 79-year-old man with a medical history of hypertension had persistent diffuse abdominal pain for 4 d. Physical examination showed stable vital signs, icteric sclera, diffuse abdominal tenderness, and muscle guarding. Laboratory tests showed hyperbilirubinemia and bandemia. Contrast computed tomography (CT) of the abdomen showed a dilated common bile duct and left subphrenic abscess. Left subphrenic abscess drainage revealed bilious fluid, and infected biloma was confirmed. Repeated abdominal CT for persistent epigastralgia after drainage showed gastric wall thickening. Esophagogastroduodenoscopy (EGD) showed an edematous, hyperemic gastric mucosa with poor distensibility. The gastric mucosal culture yielded Enterococcus faecalis. PG was diagnosed based on imaging, EGD findings, and gastric mucosal culture. The patient recovered successfully with antibiotic treatment. CONCLUSION: PG should be considered in patients with intraabdominal infection, especially from infected organs adjacent to the stomach.

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer-Its Clinical and Biological Significance in Immune Microenvironment.

Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can regulate immune responses in the tumor microenvironment (TME); however, the clinical applications of PD-L1 in early-stage colorectal cancer (CRC) remain unclear. In this study, we aimed to investigate the relationship between PD-L1 expression and survival outcome and explore its relevant immune responses in CRC. PD-L1 expression was evaluated by immunohistochemical staining to determine the tumor proportion score and combined positive score (CPS) in a Taiwanese CRC cohort. The oncomine immune response research assay was conducted for immune gene expression analyses. CRC datasets from the TCGA database were reappraised for PD-L1-associated gene enrichment analyses using GSEA. The high expression of PD-L1 (CPS ≥ 5) was associated with longer recurrence-free survival (p = 0.031) and was an independent prognostic factor as revealed by multivariate analysis. High PD-L1 expression was related to six immune-related gene signatures, and CXCL9 is the most significant overexpressed gene in differential analyses. High CXCL9 expression correlated with increased infiltration levels of immune cells in the TME, including CD8+ T lymphocytes and M1 macrophages. These findings suggest that high PD-L1 expression is a prognostic factor of early-stage CRC, and CXCL9 may play a key role in regulating PD-L1 expression.

Comparison of Different Endoscopic Methods Used for Managing Choledocholithiasis in Patients with End-Stage Renal Disease Undergoing Hemodialysis.

BACKGROUND AND AIM: Endoscopic sphincterotomy (EST), endoscopic papillary balloon dilation (EPBD), and endoscopic sphincterotomy plus balloon dilation (ESBD) are all techniques used to manage choledocholithiasis. We aim to analyze the efficacy and safety of these techniques for treating choledocholithiasis in patients undergoing hemodialysis (HD). METHODS: We performed a retrospective study of 80 patients with end-stage renal disease (ESRD) on HD who underwent endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis management between August 1st, 2012, and December 31st, 2020, at a medical center in southern Taiwan. These patients were divided into three groups: EST (n = 21), EPBD (n = 28), and ESBD (n = 31). Post-ERCP complications, including pancreatitis, bleeding, cholangitis, and perforation, were reviewed for analysis. RESULTS: There were no significant among-group differences in the rate of complete stone clearance and hospitalization day after ERCP. Patients in the EST group had a higher post-ERCP complication rate than was the case in the other groups (p = 0.016). ESBD significantly reduced post-ERCP bleeding, compared with that occurring with EST (OR 0.07; 95% CI, 0.01-0.72, p = 0.026). There were no significant among-group differences in the rates of pancreatitis and cholangitis. There were no ERCP-related perforations or deaths in this study. CONCLUSIONS: EST, EPBD, and ESBD are efficient methods for treating choledocholithiasis in ESRD patients. ESBD was found to lead to a lower risk of bleeding than EST, and the rate of pancreatitis or cholangitis was comparable for EST and EPBD. Our results suggest that ESBD is the best choice of treatment of choledocholithiasis in patients with ESRD undergoing HD.

Age, male sex, smoking and metabolic syndrome as risk factors of advanced colorectal neoplasia for fecal immunochemical test negative patients.

BACKGROUND: Fecal immunochemical test (FIT) is worldwide strategy for colorectal cancer screening. The subjects with negative FIT still have the risk of an advanced colorectal neoplasia (AN), including adenoma with villous histology, high grade dysplasia or larger than 1 cm in size, or adenocarcinoma. The study determined the risk factors associated with AN in FIT-negative subjects. METHODS: The study included asymptomatic subjects who received health checkup colonoscopy and have provided FIT study within 6 months prior to colonoscopy. The risk factors to have AN in cases with negative FIT were analyzed. The numbers of colonoscopies needed to detect one AN were calculated for the subjects with different risk factors. RESULTS: There were 1411 cases, 85 with positive FIT and 1326 with negative FIT within 6 months before colonoscopy. In FIT positive and FIT negative cases, 45.9% and 34.6% were found to have colorectal adenoma, while 20.2% and 4.6% had AN, respectively. The univariate and multivariate logistic regression analyses showed that age more than 50 years old, male sex, smoking history and metabolic syndrome were the significant risk factors to have AN in the FIT negative cases. For cases with negative FIT to have these risk factors, the number of colonoscopies needed to detect one AN was 3.7, lower than 4.5 of the cases with positive FIT. CONCLUSION: For the cases with negative FIT, colonoscopy screening should be considered for those male patients over 50 years old, with a history of smoking and metabolic syndrome to detect AN.

Real-world outcome of immune checkpoint inhibitors for advanced hepatocellular carcinoma with macrovascular tumor thrombosis.

Programmed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting. Among the 110 patients with unresectable HCC treated with PD-1 inhibitors, 34 patients with vascular metastases in the portal vein and inferior vena cava were retrospectively compared with 34 patients without tumor thrombi. The vascular response and its effect on survival were assessed. Predictors of survival were identified using multivariate analysis. Among patients achieving objective response, those with and without thrombi exhibited similar response to immunotherapy and comparable survival. Among the 34 patients with tumor thrombi, including 13 receiving PD-1 inhibitors alone and 21 receiving it in combination with tyrosine kinase inhibitors, the median overall survival was 8.9 months (95% confidence interval 3.2-12.6). The objective response rate of vascular metastasis was 52.9%, and vascular responders had a significantly longer survival than did non-responders (11.1 vs 3.9 months). Failure to obtain a vascular response correlated significantly with increased post-treatment Child-Pugh score or class. Multivariate analysis showed that vascular response was a significant positive factor for longer overall survival. Treatment-related grade 3/4 adverse events occurred in 3 (8.8%) of the patients with tumor thrombi. Immunotherapy with PD-1 inhibitors may be a feasible treatment option for HCC with tumor thrombi owing to the high response rate of tumor thrombi and favorable survival outcomes.

Safety and effectiveness of new embolization microspheres SCBRM for intermediate-stage hepatocellular carcinoma: A feasibility study.

Transarterial chemoembolization (TACE) is, currently, the recommended treatment for hepatocellular carcinoma (HCC). However, long-term chemoembolization triggers the inflammatory response and may lead to postembolization syndrome (PES). Although several types of degradable microspheres have been developed to reduce drug toxicity and PES incidence, the clinical outcomes remain unsatisfactory. Previously, we have developed a new type of spherical, calibrated, biodegradable, radiopaque microspheres (SCBRM) and demonstrated their safety and efficacy in a pig model. Thus, the goal of this feasibility study was to determine the clinical safety and efficacy of the new SCBRM in intermediate-stage HCC patients. In this study, 12 intermediate-stage HCC patients underwent TACE using SCBRM with a calibrated size of 100-250 µm. The disease control rates at 1 month and 3 months after TACE-SCBRM treatment were 100% and 75.0%, respectively. The objective response rates at 1 month and 3 months after treatment were 66.7% and 58.3%, respectively. Very few adverse events were observed with one patient developing nausea. One day after the treatment, alanine aminotransferase, alanine aminotransferase, and total bilirubin levels were slightly elevated in the patients, but all returned to baseline on day 7. The median and mean overall survival times were 33 months (interquartile range, 12.8-42.0) and 29.2 ± 14.3 months, respectively. The 1-year and 2-year survival rates were 91.7% and 58.3%, respectively. In conclusion, TACE with the new SCBRM microspheres is clinically safe and effective, and it represents a promising approach in the management of intermediate-stage HCC.

Novel upper gastrointestinal monitoring system to track upper gastrointestinal bleeding: A pilot study.

Background and study aims Early detection of upper gastrointestinal (UGI) rebleeding is not easy by observing clinical symptoms. We developed a novel UGI monitoring system and aimed to test its feasibility of continuous tracking of UGI bleeding. Patients and methods A prospective study was conducted on patients with moderate to high risk of rebleeding. The UGI monitoring system was installed to monitor their gastric contents. It would alarm if rebleeding was suspected and the physician could review the images to make a further decision. The patient's comfort level was also evaluated. Results Sixteen patients were enrolled. Rebleeding occurred in one patient and was detected by this system more than 5 hours earlier than with clinical symptoms. The interobserver reliability for reviewing the images to define the blood clearance in the stomach was excellent (intraclass correlation coefficient 0.79-0.96). The comfort level assessed by patients was 1.90 ±â€Š1.39 (on the scale of 0-5). Conclusions This pilot study demonstrated the potential of this UGI monitoring system for early detection of rebleeding.

Validation of genome-wide association study-identified single nucleotide polymorphisms in a case-control study of pancreatic cancer from Taiwan.

BACKGROUND: Due to differences in genetic background, it is unclear whether the genetic loci identified by the previous genome-wide association studies (GWAS) of pancreatic cancer also play significant roles in the development of pancreatic cancer among the Taiwanese population. METHODS: This study aimed to validate the 25 pancreatic cancer GWAS-identified single nucleotide polymorphisms (SNPs) in a case-control study (278 cases and 658 controls) of pancreatic cancer conducted in Taiwan. Statistical analyses were conducted to determine the associations between the GWAS-identified SNPs and pancreatic cancer risk. Gene-environment interaction analysis was conducted to evaluate the interactions between SNPs and environmental factors on pancreatic cancer risk. RESULTS: Among the 25 GWAS-identified SNPs, 7 (rs2816938 (~ 11 kb upstream of NR5A2), rs10094872 (~ 28 kb upstream of MYC), rs9581943 (200 bp upstream of PDX1) and 4 chromosome 13q22.1 SNPs: rs4885093, rs9573163, rs9543325, rs9573166) showed a statistically significant association with pancreatic cancer risk in the current study. Additional analyses showed two significant gene-environment interactions (between poor oral hygiene and NR5A2 rs2816938 and between obesity and PDX1 rs9581943) on the risk of pancreatic cancer. CONCLUSIONS: The current study confirmed the associations between 7 of the 25 GWAS-identified SNPs and pancreatic risk among the Taiwanese population. Furthermore, pancreatic cancer was jointly influenced by lifestyle and medical factors, genetic polymorphisms, and gene-environment interaction. Additional GWAS is needed to determine the genetic polymorphisms that are more relevant to the pancreatic cancer cases occurring in Taiwan.

HIF-1α promotes autophagic proteolysis of Dicer and enhances tumor metastasis.

HIF-1α, one of the most extensively studied oncogenes, is activated by a variety of microenvironmental factors. The resulting biological effects are thought to depend on its transcriptional activity. The RNAse enzyme Dicer is frequently downregulated in human cancers, which has been functionally linked to enhanced metastatic properties; however, current knowledge of the upstream mechanisms regulating Dicer is limited. In the present study, we identified Dicer as a HIF-1α-interacting protein in multiple types of cancer cell lines and different human tumors. HIF-1α downregulated Dicer expression by facilitating its ubiquitination by the E3 ligase Parkin, thereby enhancing autophagy-mediated degradation of Dicer, which further suppressed the maturation of known tumor suppressors, such as the microRNA let-7 and microRNA-200b. Consequently, expression of HIF-1α facilitated epithelial-mesenchymal transition (EMT) and metastasis in tumor-bearing mice. Thus, this study uncovered a connection between oncogenic HIF-1α and the tumor-suppressive Dicer. This function of HIF-1α is transcription independent and occurs through previously unrecognized protein interaction-mediated ubiquitination and autophagic proteolysis.

Epigenetic silencing of miR-137 contributes to early colorectal carcinogenesis by impaired Aurora-A inhibition.

MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis. By cell model and xenograft animal model, the enforced expression of miR-137 in colorectal cancer cells can inhibit cell proliferation and tumor formation, induce G2/M arrest, and lead to apoptosis. The expression pattern of miR-137 and Aurora-A or PTGS2 is negatively correlated in human colorectal cancer tissues and colon polyps. Those effects induced by overexpressed miR-137 can be rescued by the overexpression of Aurora-A. In summary, our study suggests that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the tendency toward to CRC formation through the impaired inhibitory effect of Aurora-A. The investigation of the regulatory mechanism of miR-137-mediated Aurora-A inhibition may shed new light on the early prognosis of cancer therapy for CRC in the future.

Development of biodegradable radiopaque microsphere for arterial embolization-a pig study.

AIM: To develop a new type of calibrated, biodegradable, and imaging detectable microsphere and evaluated its embolization safety and efficacy on pig's liver and spleen. METHODS: Six kinds of pharmaceutical excipient were combined and atomized to form our microsphere. Twenty-four male Lanyu pigs weighing 25-30 kg were used. The arteries of spleen and liver were embolized with Gelfoam, Embosphere, or our microsphere. The serum biochemical tests, computed tomography (CT), liver perfusion scan, and tissue microscopy examination were done to evaluate the safety and efficacy of embolization. RESULTS: Radiopaque microspheres with a size ranging from 300 to 400 µm were produced. Embolization of hepatic and splenic artery of pigs with our microsphere significantly reduced the blood flow of liver and resulted in splenic infarction. The follow-up CT imaging and the microscopic examination showed intraarterial degradation of Gelfoam and microsphere. The blood tests demonstrated insignificant changes with regards to liver and renal functions. CONCLUSION: Our microspheres, with the unique characteristics, can be used for transcatheter arterial embolization with effects equivalent to or better than Gelfoam and Embosphere in pigs.

Electromagnetic thermotherapy for deep organ ablation by using a needle array under a synchronized-coil system.

Thermal ablation by using electromagnetic thermotherapy (EMT) has been a promising cancer modality in recent years. It has relatively few side effects and has therefore been extensively investigated for a variety of medical applications in internal medicine and surgery. The EMT system applies a high-frequency alternating electromagnetic field to heat up the needles which are inserted into the target tumor to cause tumor ablation. In this study, a new synchronized-coil EMT system was demonstrated, which was equipped with two synchronized coils and magnetic field generators to provide a long-range, penetrated electromagnetic field to effectively heat up the needles. The heating effect of the needles at the center of the two coils was first explored. The newly designed two-section needle array combined with the synchronized-coil EMT system was thus demonstrated in the in vitro and in vivo animal experiments. Experimental data showed that the developed system is promising for minimally invasive surgery since it might provide superior performance for thermotherapy in cancer treatment.

Electromagnetic thermotherapy system with needle arrays: a practical tool for the removal of cancerous tumors.

Thermotherapy has been a promising method to treat tumor. In recent years, electromagnetic thermotherapy (EMT) has been extensively investigated and holds the potential for a variety of medical applications including for cancer treatment when combined with minimally invasive surgery approach. In this study, an alternating electromagnetic frequency was provided by an EMT system to heat up stainless steel needle arrays which were inserted into the target tumor to a high temperature, therefore leading to local ablation of the tumor. A new two-section needle-array apparatus was further demonstrated to encompass the tumor to prevent the tumor cells to spread after the treatment process. By using the needle-array insertion apparatus, there is no limitation of the treatment area; this method could, therefore, be applied for tumors that are larger than 6 cm. It was first successfully demonstrated in the in vitro experiments on porcine livers. Then an in vivo experiment was directly conducted on pigs. The two-section needle array incorporated with the needle-array apparatus and EMT was demonstrated to be promising for no-touch isolation treatment of cancerous tumors.

An electromagnetic thermotherapy system with a deep penetration depth for percutaneous thermal ablation.

Thermal ablation has been a promising method to remove the cancerous tissues. Electromagnetic-based thermotherapy has been extensively investigated for a variety of medical applications recently. In this study, a prototype electromagnetic thermotherapy system has been developed with a new coil design and a two-section needle. The coil can generate an alternating electromagnetic field (EMF) with a deep penetration depth to remotely heat the needle which is located up to 15 cm away, enabling percutaneous thermal ablation. Several important parameters, including the heating effects of the needle at different positions, the intensity of the EMF and the induced temperature distribution on the surrounding tissue, are first explored. An in vitro animal experiment has also been performed which shows EMF-induced ablation in a porcine liver by the needle. Furthermore, an in vivo experiment on an animal model (a New Zealand white rabbit) is also conducted in the study. Thus, the two-section needle combined with the coil-generated EMF has been demonstrated to be a promising thermotherapy system for percutaneous thermal ablation.