Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HCV core protein is considered as a positive regulator of telomerase ...activity. In this study, we focused on the deregulated microRNA-138 (miR-138) in HCV-associated HCC. Differential expression of miR-138 was determined by TaqMan quantitative real-time PCR. The target gene of miR-138 was verified by luciferase reporter assay, quantitative real-time PCR, and Western blotting. Moreover, three assays based on telomerase activity, cell proliferation, and senescence-associated β-galactosidase activity were performed. The correlation analysis revealed a significantly negative correlation between miR-138 and telomerase reverse transcriptase (TERT) mRNA expression in HCC. Further, we showed that mature HCV core protein of 173 amino acids, but not full-length form of 191 amino acids, suppressed miR-138 expression. TERT was verified as a direct target of miR-138 in HCC cells. Furthermore, TERT-targeting miR-138 supplementation can prevent HCV core protein from repressing HCC cell replicative senescence. Collectively, HCV core protein can enhance TERT protein expression through downregulating TERT-targeting miR-138 expression, which in turn inhibits HCC cell replicative senescence. This study may further help our understanding on the pathogenic mechanisms of HCV core protein in HCV-associated HCC development.
Key message
miR-138 is downregulated in HCV-associated HCC.
Mature HCV core protein plays a pathogenic role in suppressing miR-138 expression.
Telomerase reverse transcriptase represents a direct target of miR-138 in HCC cells.
miR-138 promotes HCC cell senescence, suggesting potential for HCC treatment.
To evaluate the efficacy of drug-eluting beads loaded with irinotecan (DEBIRI) in colorectal cancer (CRC) patients with synchronous liver-only metastases non-responsive to bevacizumab-based ...chemotherapy (BBC).
Fifty-eight patients were enrolled in this study. Treatment response to BBC and DEBIRI were determined by the morphological criteria and Choi's criteria, respectively. Progression-free survival (PFS) and overall survival (OS) were recorded. The correlation between pre-DEBIRI CT parameters and treatment response to DEBIRI was analyzed.
CRC patients were divided into the BBC responsive group (R group) (
= 16) and the non-responsive group (
= 42), which was further divided into the NR group (23 patients who did not receive DEBIRI) and the NR+DEBIRI group (19 patients who received DEBIRI after failing BBC). Among the R, NR and NR+DEBIRI groups, the median PFS were 11, 12, and 4 months, respectively (
< 0.01); median OS were 36, 23, and 12 months, respectively (
= 0.01). In the NR+DEBIRI group, 33 metastatic lesions were treated with DEBIRI, of which 18 (54.5%) reached objective response. The receiver operating characteristic curve showed that the contrast enhancement ratio (CER) before DEBIRI could predict objective response (AUC = 0.737,
< 0.01).
In CRC patients, DEBIRI can achieve acceptable objective response for liver metastases non-responsive to BBC. However, this locoregional control does not prolong survival. The pre-DEBIRI CER can predict OR in these patients.
DEBIRI can act as an acceptable locoregional management in CRC patients with liver metastases non-responsive to BBC, and the pre-DEBIRI CER is a potential indicator of locoregional control.
Approximately 10-40% of hepatocellular carcinoma (HCC) patients have definite vascular invasion at the time of diagnosis. Without curative treatment options, these patients have an abysmal prognosis ...with a median survival of only a few months following systemic therapy. However, supportive evidence of combining multiple locoregional treatments with systemic therapy is limited. This study compared the outcomes of sorafenib alone versus multimodality therapy with sorafenib, radiotherapy (RT), and transarterial chemoembolization (TACE) in advanced HCC patients with macrovascular invasion (MaVI).
The process took place over a nine-year period between March 2009 and October 2017, wherein 78 HCC patients with MaVI who underwent either sorafenib therapy alone (n = 49) or combined sorafenib/RT/TACE (n = 29) therapy were chosen for the retrospective study. We compared the overall survival (OS) between the two groups using the Cox regression hazard model and adjusted imbalances using propensity score matching (PSM).
At the last follow-up, 76 patients had died, with a median follow-up time of 4.8 months for all patients and 31 months for those who were alive. Patients treated with sorafenib/RT/TACE had superior OS compared to those treated with sorafenib alone, showing a median survival of 9.3 vs. 2.7 months and a one-year survival of 37.1% vs. 6.1% (
< 0.001). In the multivariable analysis, new diagnosis or recurrence of HCC and treatment modalities (sorafenib alone vs. sorafenib/RT/TACE) were independent prognostic factors for OS. Compared to patients treated with sorafenib alone, significantly better OS was further verified using PSM (
< 0.001) in patients who received multiple therapeutic modalities.
Multimodality therapy with sorafenib/RT/TACE increased OS threefold versus sorafenib therapy alone in HCC patients with MaVI. This study offers promising benefits of combined locoregional and systemic therapy for advanced HCC in current patient management and prospective clinical trials.
Ste20-related protein proline/alanine-rich kinase (SPAK) affects cell proliferation, differentiation, and transformation, and sodium and chloride transport in the gut. However, its role in gut injury ...pathogenesis is unclear.
We determined the role of SPAK in chemotherapy-induced intestinal mucositis using
and
models.
Using SPAK-knockout (KO) mice, we evaluated the severity of intestinal mucositis induced by 5-fluorouracil (5-FU) by assessing body weight loss, histological changes in the intestinal mucosa, length of villi in the small intestine, pro-inflammatory cytokine levels, proliferative indices, and apoptotic indices. We also evaluated changes in gut permeability and tight junction-associated protein expression. Changes in cell permeability, proliferation, and apoptosis were assessed in SPAK siRNA-transfected 5FU-treated IEC-6 cells.
5-FU-treated SPAK-KO mice exhibited milder intestinal mucositis, reduced pro-inflammatory cytokine expression, increased villus length, good maintenance of proliferative indices of villus cells, decreased apoptotic index of enterocytes, reduced gut permeability, and restoration of tight junction protein expression (
. 5-FU-treated wild-type mice). Under
conditions, siRNA-mediated SPAK-knockdown in IEC-6 cells decreased cell permeability and maintained homeostasis following 5-FU treatment.
SPAK deficiency attenuated chemotherapy-induced intestinal mucositis by modulating gut permeability and tight junction-associated protein expression and maintaining gut homeostasis in murine small intestinal tissues following gut injury. The expression of SPAK may influence the pathogenesis of chemotherapy-induced intestinal mucositis.
Colonic angiodysplasia (AGD) is a common cause of gastrointestinal bleeding. However, information on the characteristics and prevalence of colonic AGD is limited. We determined the clinical features ...of and risk factors for active bleeding in colonic AGD in a Taiwanese population.
From February 2007 to December 2016, 13,047 patients undergoing 16,760 colonoscopies at the Tri-Service General Hospital were included in this study. Eighty-four patients were diagnosed with AGD. We conducted a retrospective study by analyzing the medical records of these patients. The clinical features and endoscopic findings were evaluated. Furthermore, we distinguished colonic AGD into bleeding and non-bleeding types and identified the risk factors for bleeding in colonic AGD.
In our study, the prevalence of colonic AGD was 0.6% among all patients who received colonoscopy. Among patients with colonic AGD, we found that many were aged; in all, 58.3% of patients with colonic AGD were older than 65 years. More than half of the patients had hypertensive cardiovascular disease (53.6%) and the AGD lesions were predominantly located in the left-sided colon (41.7%). We analyzed several factors to identify those associated with bleeding colonic AGD. Our results indicated that age (p < 0.001), hypertension (p = 0.020), atrial fibrillation (p = 0.027), and in-patient status (p = 0.006) were significant factors associated with active bleeding lesions. On multivariate analysis, old age was the only significant risk factor.
Angiodysplastic lesions in Taiwanese patients were predominantly identified in the left-sided colon. Old age was an independent risk factor associated with active bleeding in colonic angiodysplasia.
Hepatocellular carcinoma accounts for approximately 90% of primary liver cancers and hepatitis virus was believed to have the potential for altering the pathogenesis of arteriosclerosis. However, the ...influence of the hepatitis virus on coronary artery disease or cerebral vascular disease remains unclear. This study used the Taiwan National Health Insurance Research Database to clarify the virus-associated risk of coronary artery disease and cerebral vascular disease in patients with hepatocellular carcinoma (HCC).
A total of 188,039 HCC individuals, age 20 years or older, were enrolled from the Longitudinal Health Insurance Database between 2000 and 2017 for cohort analysis. A total of 109,348 with hepatitis B virus (HBV) infection, 37,506 with hepatitis C virus (HCV) infection, 34,110 without HBV or HCV, and 7075 with both HBV and HCV were recorded. Statistically, propensity score matched by sex, age, and index year at a ratio of 15:5:5:1 and a sensitivity test using multivariable Cox regression were used.
The risk of coronary artery disease in the HCV-related HCC group was 1.516-fold (95% CI: 1.328-2.034,
< 0.001) higher than in the HBV-related HCC group, followed by the HBV/HCV-related HCC group and the non-B/C HCC group; the cerebral vascular disease risk in the HCV-related HCC group was 1.467-fold higher than in the HBV-related HCC group (95% CI: 1.335 to 1.786,
< 0.001), followed by the HBV/HCV-related HCC group and the non-B/C HCC group.
Hepatitis C virus infection was found to have a higher risk of developing coronary artery disease or cerebral vascular disease in patients with hepatocellular carcinoma. For patients with hepatocellular carcinoma, our findings warrant the importance in preventing artherosclerotic disease in the setting of hepatitis C virus infection.
Pancreatic cancer is difficult to diagnose in an early stage, and has the highest mortality of all types of cancer. Obesity, high body mass index, and increased abdominal girth are established risk ...factors. Some studies have postulated that there is a correlation between organ steatosis and pancreatic cancer. This study aims to explore whether nonalcoholic fatty liver disease (NAFLD) is a risk factor and a prognostic factor for pancreatic cancer. The study enrolled 557 patients (143 with and 414 without pancreatic cancer) who were diagnosed between January 2009 and December 2013. We reviewed the abdominal computed tomographic scans of the patients to confirm the diagnosis of NAFLD. Clinical parameters, laboratory data, and personal information were analyzed. NAFLD is an independent risk factor for pancreatic cancer according to adjusted multivariate logistic regression analysis (OR 2.63, 95% CI 1.24–5.58,
p
= 0.011). The Kaplan–Meier survival curve reveals that patients without NAFLD have longer survival than patients with NAFLD (
p
= 0.005, log-rank test). NAFLD is positively correlated with pancreatic cancer, a result suggesting that NAFLD may increase the incidence and risk of pancreatic cancer. Patients with pancreatic cancer and NAFLD have poorer overall survival than patients without NAFLD, perhaps, because dysregulated cytokine status leads to progression of pancreatic cancer. NAFLD may be a prognostic factor for pancreatic cancer.
Most patients with partial intestinal obstruction can be managed without surgical intervention. Here, we report the case of a patient who presented with partial intestinal obstruction. He had been ...diagnosed with high-grade urothelial cell carcinoma (UCC) 1.5 years previously, for which the surgery and adjuvant chemotherapy had been successfully performed. He showed a poor response to medical treatment for the partial intestinal obstruction, and surgery provided only a short‑term benefit. Such cases of intractable small-bowel obstruction are infrequent and pose a challenge to clinicians. Although very rare, the possibility of UCC metastasis to the gastrointestinal tract should be considered in the differential diagnosis of refractory intestinal obstruction and history of UCC.
Sedation esophagogastroduodenoscopy (EGD) has become more prevalent in many countries. However, owing to the limitation of health insurance payment for sedation EGD in Taiwan, non-sedation EGD still ...accounts for the majority of cases. This study was aimed to explore the differences between the sedation and non-sedation groups in terms of endoscopic findings, such as detection rate of gastric polyp of any size, number of detected gastric polyps, and location of the gastric polyps detected.We enrolled 10,940 patients who underwent EGD between January 1, 2016 and December 31, 2016 at the Tri-Service General Hospital; among the patients, 1900 received intravenous sedation (IVS) and 9040 did not. The data reviewed included demographics, parameters of the polyp (number, size, and location), and pathology.Compared with the non-sedation group, the sedation group had a higher overall polyp detection rate (P < .001); a greater number of detected polyps (Odds ratio 1.50, P = .007); and a higher detection rate of smaller polyps, such as fundic gland polyp, and hyperplastic polyp (P < .001). Among the pathological findings, gastric neuroendocrine tumor (NET) was detected using EGD in 2 cases and manifested as small polyps (<0.05 cm), and it showed significantly better detection rates in the sedation EGD group than in the non-sedation EGD group (P = .002).Sedation EGD could enhance a patients willingness and cooperation during EGD. Furthermore, sedation EGD increased the detection rates of small gastric polyps and was more likely to enable identification of unusual findings, such as gastric NET.
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