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1.
Article in English | MEDLINE | ID: mdl-38840444

ABSTRACT

BACKGROUND AND AIM: Delayed endoscopic sphincterotomy-related bleeding (ES bleeding) is an unavoidable adverse event (AE) that can have serious ramifications. Intraoperative ES bleeding, which stops spontaneously in most cases, is a known risk factor for delayed bleeding. This study aimed to examine the preventive effect of a novel self-assembling peptide (SAP) for delayed ES bleeding in patients who attained spontaneous hemostasis after intraoperative ES bleeding. METHODS: A total of 1507 patients met the eligibility criteria for inclusion in this study. The rates of delayed ES bleeding and AE besides bleeding were compared between patients administered the SAP (SAP group) and those who were simply observed after spontaneous hemostasis of intraoperative ES bleeding (control group). Propensity score matching was performed to adjust for differences between the groups. RESULTS: The rate of delayed ES bleeding was significantly lower in the SAP group than that in the control group (0.9% vs 3.8%, P = 0.044). The rates of AEs other than bleeding were 2.4% and 3.8% in the SAP and control groups, respectively, and the difference lacked statistical significance (P = 0.481). Multivariate analysis revealed that the use of SAP was significantly associated with a lower frequency of delayed ES bleeding (odds ratio, 0.35; 95% confidence interval, 0.13-0.98; P = 0.047). CONCLUSIONS: Self-assembling peptide may be a simple, safe, and useful way to reduce the risk of delayed ES bleeding in patients who experienced intraoperative ES bleeding and obtained subsequent spontaneous hemostasis.

2.
Gastrointest Endosc ; 97(2): 282-290.e1, 2023 02.
Article in English | MEDLINE | ID: mdl-36220379

ABSTRACT

BACKGROUND AND AIMS: Endoscopic biliary radiofrequency ablation (RFA) may be an option for the treatment of ingrowth occlusion after self-expandable metal stent (SEMS) deployment; however, its utility remains uncertain. This study aimed to examine the feasibility of RFA for the palliation of ingrowth after bilateral SEMS placement in patients with malignant hilar biliary obstruction. METHODS: This prospective, single-center, pilot study enrolled 30 patients who met the eligibility criteria between April 2020 and March 2022. Study outcomes were technical success, clinical success, recurrent biliary obstruction (RBO), and adverse events (AEs) besides RBO associated with RFA for ingrowth occlusion. Furthermore, factors predictive of clinical success were evaluated. RESULTS: Technical and clinical success rates were 93.3% (28/30) and 71.4% (20/28), respectively. The rates of early and late AEs were 6.7% (2/30) and 10.0% (2/20), respectively. The incidence rate of RBO after RFA was 45.0% (9/20), and the median time to RBO was 163 days. Multivariate analysis of the factors affecting clinical success revealed a positive association between the recanalization diameter on the ingrown part within the SEMS (odds ratio, 1.13; 95% confidence interval, 1.01-1.26; P = .038). The calculated optimal cutoff for the ratio of the recanalization diameter to the SEMS diameter for predicting clinical success was 51.1%. CONCLUSIONS: Endoscopic biliary RFA elicited promising results, with good long-term stent patency and without the requirement of any additional stent placement, for the palliation of ingrowth occlusion after bilateral SEMS placement. However, the clinical success rate was insufficient, necessitating improvements in the future. (Clinical trial registration number: UMIN000040154.).


Subject(s)
Cholestasis , Stents , Humans , Cholestasis/etiology , Cholestasis/surgery , Metals , Pilot Projects , Prospective Studies , Stents/adverse effects , Treatment Outcome
3.
Dig Dis Sci ; 68(5): 2090-2098, 2023 05.
Article in English | MEDLINE | ID: mdl-36350476

ABSTRACT

BACKGROUND: Endoscopic ultrasound-guided hepaticogastrostomy with antegrade stenting (EUS-HGAS) is a promising therapeutic option for malignant distal biliary obstruction (MDBO) in the event of transpapillary approach failure. Eliminating the fistula dilation step may further decrease the incidence of adverse events (AE) and simplify the procedure. AIMS: This study focused on MDBO associated with pancreatic cancer and aimed to examine the utility of EUS-HGAS without the use of any dilation devices. METHODS: This retrospective study investigated consecutive patients in whom the transpapillary approach had failed or was difficult, and who underwent EUS-HGAS without dilation device usage, using a tapered small-diameter catheter, ultrathin delivery system, and tapered dedicated plastic stent. The outcomes of this study included the technical success, clinical success, AE incidence, and recurrent biliary obstruction (RBO) associated with the procedure. RESULTS: During the study period, EUS-HGAS without dilation device usage was attempted for 57 patients with MDBO due to pancreatic cancer. The technical and clinical success rates were 91.2% (52/57) each. The median procedural time was 25 min. The rates of early and late AE besides RBO were 3.5% (2/57) and 1.9% (1/52), respectively. The incidence rate of RBO was 30.8% (16/52), and the median time to RBO was 245 days. The rate of successful endoscopic reintervention for RBO via the fistula was 100% (16/16). CONCLUSIONS: EUS-HGAS without the use of dilation devices showed good technical feasibility with a low AE rate. It may be a useful option for MDBO associated with pancreatic cancer when the transpapillary approach is difficult.


Subject(s)
Cholestasis , Pancreatic Neoplasms , Humans , Retrospective Studies , Dilatation , Treatment Outcome , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholestasis/diagnostic imaging , Cholestasis/etiology , Cholestasis/surgery , Stents/adverse effects , Endosonography/methods , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/surgery , Drainage/methods , Ultrasonography, Interventional/adverse effects , Pancreatic Neoplasms
4.
Dig Dis Sci ; 68(12): 4449-4455, 2023 12.
Article in English | MEDLINE | ID: mdl-37831399

ABSTRACT

BACKGROUND: Acute cholecystitis is a significant adverse event after self-expandable metal stent (SEMS) placement for malignant biliary obstruction (MBO); however, no appropriate treatment strategy has been established for its management. AIMS: This study aimed to examine the feasibility and utility of endoscopic ultrasound-guided naso-gallbladder drainage (EUS-NGBD) for the management of acute cholecystitis occurring after SEMS placement. METHODS: This retrospective study investigated consecutive patients with acute cholecystitis after SEMS placement for unresectable MBO, in whom EUS-NGBD was attempted. The study outcomes included technical success, clinical success, procedure time, adverse event, and cholecystitis recurrence, associated with the procedure. RESULTS: During the study period, EUS-NGBD was performed for SEMS-related acute cholecystitis in 30 patients with MBO. The technical and clinical success rates were 96.7% (29/30) and 96.6% (28/29), respectively. The median procedure time was 15 min, and rate of procedure-related adverse event was 3.3% (1/30). The median duration from the procedure to tube removal was 9 days. No adverse events were observed after removal. The median hospitalization duration after the procedure was 14 days, and the median duration to the (re-)start of chemotherapy from cholecystitis onset was 13 days. The median overall survival after EUS-NGBD was 123 days, and the rate of cholecystitis recurrence until death was 4.2% (1/28). CONCLUSIONS: This study demonstrated that EUS-NGBD possesses good technical and clinical feasibility with an acceptable adverse event rates and short hospitalization and chemotherapy withdrawal period. Therefore, EUS-NGBD may be a good option for the treatment of SEMS-related cholecystitis in patients with MBO.


Subject(s)
Cholecystitis, Acute , Cholecystitis , Cholestasis , Neoplasms , Humans , Retrospective Studies , Treatment Outcome , Cholecystitis, Acute/diagnostic imaging , Cholecystitis, Acute/surgery , Endosonography/methods , Drainage/adverse effects , Drainage/methods , Cholecystitis/etiology , Cholecystitis/therapy , Stents/adverse effects , Catheters , Ultrasonography, Interventional/adverse effects , Cholestasis/etiology
5.
Gastrointest Endosc ; 95(4): 717-722, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34762919

ABSTRACT

BACKGROUND AND AIMS: Balloon enteroscopy-assisted ERCP (BE-ERCP) is useful for treating pancreatobiliary disease in patients with surgically altered anatomy (SAA); however, biliary cannulation, including the precut technique, is often challenging. This study aimed to examine the feasibility of scissor-type knife precutting (SKP) during BE-ERCP in patients with SAA. METHODS: This retrospective study investigated consecutive patients who underwent BE-ERCP and SKP for difficult biliary cannulation between 2016 and 2021. The study outcomes included the technical success and adverse event rates associated with SKP during BE-ERCP. RESULTS: During the study period, 125 patients with native duodenal papillae underwent BE-ERCP, and the papilla was reached in 116 patients. The success rate of biliary cannulation with the standard cannulation approach alone was 67.2% (78/116), which increased to 77.6% (90/116) with the inclusion of advanced cannulation techniques besides precutting and further improved to 87.9% (102/116) with the addition of needlife precutting. SKP was attempted in 12 patients in whom all other cannulation approaches were difficult or resulted in failure. The technical success rate of SKP was 66.7% (8/12); thus, SKP increased the final success rate of biliary cannulation to 94.8% (110/116). The rate of adverse events associated with SKP was 8.3% (1/12). CONCLUSIONS: This is the first study to report the use of the SKP technique for difficult biliary cannulation in patients with SAA, which may serve as a useful option for salvage cannulation during BE-ERCP.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Sphincterotomy, Endoscopic , Balloon Enteroscopy , Catheterization/methods , Cholangiopancreatography, Endoscopic Retrograde/methods , Humans , Retrospective Studies , Sphincterotomy, Endoscopic/adverse effects , Sphincterotomy, Endoscopic/methods
6.
Endoscopy ; 54(10): 987-992, 2022 10.
Article in English | MEDLINE | ID: mdl-35144287

ABSTRACT

BACKGROUND : Endoscopic stone extraction is often challenging in patients with a significant lower bile duct corner pocket, where small stones are likely to escape and become impacted. This study aimed to determine the utility of different types of baskets for retrieving corner pocket stones. METHODS : Seven types of retrieval baskets were evaluated on silicone models. The study outcomes included the characteristics of each basket and technical success rates associated with the retrieval of stones impacted in the corner pocket. RESULTS : The overall success rate was only 27.5 %, with significant differences between the baskets (P < 0.001). Only three baskets yielded successful removal. The success rates were 10 %, 25 %, and 70 % with the 8-wire Nitinol Basket, RASEN, and VorticCatch V, respectively, all of which are helical eight-wire baskets. RASEN and VorticCatch V share similar characteristics, including a strong spiral wire and smaller interwire spaces at their distal ends. The addition of rotation significantly increased the success rate to 80 % with the 8-wire Nitinol Basket (P < 0.001) and 90 % with RASEN (P < 0.001). CONCLUSIONS : Robust helical eight-wire baskets with smaller interwire spaces at the tip may be effective for extracting corner pocket stones, while the addition of rotational motion may improve the efficacy of retrieval.


Subject(s)
Calculi , Gallstones , Alloys , Bile Ducts , Catheters , Cholangiopancreatography, Endoscopic Retrograde/methods , Gallstones/surgery , Humans , Silicones
7.
Dig Dis Sci ; 67(8): 4181-4187, 2022 08.
Article in English | MEDLINE | ID: mdl-34410572

ABSTRACT

BACKGROUND: Endoscopic radiofrequency ablation (RFA) is expected to prolong stent patency for malignant biliary obstruction (MBO). However, its feasibility when used in conjunction with a balloon enteroscope (BE) in patients with surgically altered anatomy (SAA) remains unknown. AIMS: This study aimed to investigate the feasibility of RFA combined with metal stent insertion under BE guidance for MBO in patients with SAA. METHODS: Thirty-seven patients who underwent treatment between October 2016 and January 2021 and met the eligibility criteria were investigated retrospectively. Study outcomes included technical and clinical success, recurrent biliary obstruction (RBO), and other adverse events besides RBO associated with RFA with metal stent placement using BE. RESULTS: Technical and clinical success rates were 100% (37/37) each. The rates of early and late adverse events were 8.1% (3/37) and 8.1% (3/37), respectively. RBO occurred in 32.4% (12/37) of the patients, and the median time to RBO was 296 days. The cause of RBO was ingrowth in eight patients, overgrowth in three patients, and indeterminate in one patient. All reinterventions for RBO were successful using the BE approach; all ingrowths, except one, were recanalized using additional RFA without additional stent placement. The frequency of reintervention-related adverse events was 9.1% (1/11). The median time to RBO after reintervention was 166 days. CONCLUSIONS: This study demonstrated the technical safety and feasibility as well as good long-term outcomes of endobiliary RFA combined with metal stent placement under BE guidance. This approach may be a useful option for treating MBO in patients with SAA.


Subject(s)
Bile Duct Neoplasms , Catheter Ablation , Cholestasis , Bile Duct Neoplasms/surgery , Catheter Ablation/adverse effects , Cholestasis/etiology , Humans , Retrospective Studies , Stents/adverse effects , Treatment Outcome
8.
Dig Dis Sci ; 67(7): 3298-3304, 2022 07.
Article in English | MEDLINE | ID: mdl-34125338

ABSTRACT

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) is the first-line chemotherapeutic regimen for metastatic pancreatic cancer (MPC); however, there are concerns regarding its safety in patients undergoing biliary stent placement. This study aimed to examine the tolerability and efficacy of GnP in MPC patients who underwent biliary stent placement. METHODS: A total of 105 MPC patients who had received GnP treatment between 2015 and 2020 were included and investigated. The patients were divided into two groups: those undergoing biliary stent placement for symptomatic biliary obstruction (BO) (With-BO group) and those without biliary stent placement (Without-BO group). The best tumor response, overall survival (OS), and adverse events in each group were compared. RESULTS: The partial response, stable disease, and progressive disease rates were 22%, 61%, and 14.6% in the With-BO group, and 26.6%, 46.9%, and 21.9% in the Without-BO group, respectively, with no significant differences. The median OS was 12.2 months and 14.6 months in the With-BO and Without-BO groups, respectively (P = 0.483). Grade 3 or higher biliary tract-related events were significantly more common in the With-BO group (41.5%) than in the Without-BO group (1.6%) (P < 0.001), but all events were managed successfully by urgent intervention. The rates of any treatment-related toxicities, including febrile neutropenia, were not significantly different, and there were no chemotherapy-related deaths in either group. CONCLUSIONS: GnP can be as tolerable and effective in MPC patients with biliary stents as in those without biliary stents. However, careful management and appropriate reintervention to treat biliary tract-related adverse events are required.


Subject(s)
Biliary Tract , Pancreatic Neoplasms , Albumins/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biliary Tract/pathology , Deoxycytidine/analogs & derivatives , Humans , Paclitaxel/adverse effects , Pancreatic Neoplasms/drug therapy , Stents , Treatment Outcome , Gemcitabine
9.
Dig Dis Sci ; 66(4): 1291-1296, 2021 04.
Article in English | MEDLINE | ID: mdl-32440744

ABSTRACT

BACKGROUND: The risk related to endoscopic retrograde cholangiopancreatography (ERCP) in patients with Eastern Cooperative Oncology Group performance status (PS) 4 is uncertain and remains a concern. AIMS: We aimed to examine the safety and efficacy of ERCP in patients with PS4 compared to those in patients with PS0-3. METHODS: A total of 1845 patients met the eligibility criteria for study inclusion between 2014 and 2018. The patients were divided into two groups: PS0-3 and PS4 groups. The adverse event and therapeutic success rates in each group were compared. Propensity score matching was performed to adjust for differences between the groups. RESULTS: The therapeutic success rate was 96% in both groups. The overall adverse event rate was 6% and 10% in the PS0-3 and PS4 groups, respectively, showing no significant difference (P = 0.272). Although the rates of pancreatitis, bleeding, perforation, and cholangitis were equivalent in both groups, the pulmonary adverse event rate was significantly higher in the PS4 group (5% vs. 0.4%; P = 0.006). Severe adverse events were also significantly more frequent in the PS4 group (8% vs. 2%; P = 0.012). Multivariate analyses showed that long procedure time was a significant risk factor for adverse events in patients with PS4 (odds ratio, 10.70; 95% CI 1.30-87.70; P = 0.028). CONCLUSIONS: Although ERCP can be performed effectively in patients with PS4, the risk of pulmonary and severe adverse events is high. Prolonged procedures should be avoided in patients with PS4.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/methods , Cholangitis/diagnostic imaging , Pancreatitis/diagnostic imaging , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/standards , Cholangitis/surgery , Female , Humans , Male , Middle Aged , Pancreatitis/surgery , Retrospective Studies , Risk Factors , Treatment Outcome , Young Adult
10.
Int J Mol Sci ; 22(8)2021 Apr 11.
Article in English | MEDLINE | ID: mdl-33920431

ABSTRACT

Corticotropin-releasing factor (CRF) in the brain acts on physiological and pathophysiological modulation of the hepatobiliary system. Central CRF administration aggravates experimental acute liver injury by decreasing hepatic blood flow. Conversely, minimal evidence is available regarding the effect of centrally acting CRF on hepatic lipid metabolism and inflammation. We examined whether central CRF affects hepatic lipid metabolism and inflammation-related gene expression in rats. Male Long Evans rats were intracisternally injected with CRF (10 µg) or saline. Rats were sacrificed 2 h, 6 h, and 24 h after the CRF injection, the liver was isolated, and mRNA was extracted. Next, hepatic lipid metabolism and inflammation-related gene expression were examined. Hepatic SREBF1 (sterol regulatory element-binding transcription factor 1) mRNA levels were significantly increased 6 h and 24 h after intracisternal CRF administration when compared with those in the control group. Hepatic TNFα and IL1ß mRNA levels increased significantly 6 h after intracisternal CRF administration. Hepatic sympathectomy or guanethidine treatment, not hepatic branch vagotomy or atropine treatment, inhibited central CRF-induced increase in hepatic SREBF1, TNFα and IL1ß mRNA levels. These results indicated that central CRF affects hepatic de novo lipogenesis and inflammation-related gene expression through the sympathetic-noradrenergic nervous system in rats.


Subject(s)
Corticotropin-Releasing Hormone/pharmacology , Gene Expression Regulation/drug effects , Hepatitis/metabolism , Lipid Metabolism/drug effects , Liver/metabolism , Animals , Hepatitis/pathology , Inflammation/metabolism , Inflammation/pathology , Liver/pathology , Male , Rats , Rats, Long-Evans
11.
Endoscopy ; 52(7): 595-599, 2020 07.
Article in English | MEDLINE | ID: mdl-32208498

ABSTRACT

BACKGROUND: The effectiveness of endobiliary radiofrequency ablation (RFA) is still uncertain, especially in patients with malignant hilar biliary obstruction (MHBO). We examined the efficacy of endobiliary RFA followed by bilateral self-expandable metal stent (SEMS) placement for unresectable MHBO. METHODS: 41 patients met the eligibility criteria for study inclusion. We evaluated the technical success, functional success, and recurrent biliary obstruction (RBO) associated with RFA with bilateral SEMS placement. RESULTS: The technical and functional success rates were both 95.1 % (39/41). The RBO rate was 38.5 % (15/39), and the median time to RBO was 230 days. Stricture length was positively correlated with time to RBO in the multivariate analysis (P = 0.03). The median time to RBO was significantly longer in patients with strictures > 15 mm in length than in those with strictures ≤ 15 mm (314 vs. 156 days; P = 0.02). CONCLUSIONS: The present study showed that endobiliary RFA with bilateral SEMS placement achieved good results, but selection of patients with an appropriate stricture length may be needed to obtain a sufficient ablative effect.


Subject(s)
Bile Duct Neoplasms , Cholestasis , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/surgery , Cholestasis/etiology , Cholestasis/surgery , Humans , Radiofrequency Ablation/adverse effects , Retrospective Studies , Stents , Treatment Outcome
12.
Dig Dis Sci ; 65(11): 3324-3331, 2020 11.
Article in English | MEDLINE | ID: mdl-31950313

ABSTRACT

BACKGROUND: Placement of covered self-expandable metallic stent (CSEMS) for post-endoscopic sphincterotomy (ES) bleeding achieves excellent hemostasis results. Although CSEMS placement is typically performed after failure of conventional endoscopic combination therapy, its excellent outcomes may justify earlier placement. AIMS: We aimed to examine the efficacy of "early" CSEMS placement for massive post-ES bleeding. METHODS: The medical records of 2750 patients who underwent ES between 2005 and 2019 were reviewed retrospectively, and 61 patients who developed massive post-ES bleeding were enrolled. These patients were divided into those who underwent early CSEMS placement (E-CSEMS group) and those who underwent conventional endoscopic combination therapy (Conventional group). The outcomes of hemostasis procedures were compared between the groups. RESULTS: The primary success rates of endoscopic hemostasis were 100% (21/21) and 98% (39/40) in the E-CSEMS group and Conventional group, respectively, without significant differences (P = 1.000). However, in the E-CSEMS group, re-bleeding was significantly less frequent (5% vs. 31%; P = 0.023), the median hemostasis procedure time was significantly shorter (14 min vs. 26 min; P < 0.001), and transfusion after initial hemostasis treatment was less commonly required (10% vs. 38%; P = 0.034). Multivariate analyses showed that hemodialysis was associated with a significantly higher re-bleeding rate (P = 0.029), while CSEMS placement was associated with a significantly lower re-bleeding rate (P = 0.039). CONCLUSIONS: Early CSEMS placement may be effective for improving the clinical outcomes of massive post-ES bleeding by decreasing re-bleeding and the extent of bleeding.


Subject(s)
Hemostasis, Endoscopic/methods , Postoperative Hemorrhage/prevention & control , Self Expandable Metallic Stents , Sphincterotomy, Endoscopic , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies
13.
Int J Mol Sci ; 21(24)2020 Dec 10.
Article in English | MEDLINE | ID: mdl-33321735

ABSTRACT

The autonomic nervous system, consisting of sympathetic and parasympathetic branches, plays an important role in regulating metabolic homeostasis. The sympathetic nervous system (SNS) regulates hepatic lipid metabolism by regulating adrenergic receptor activation, resulting in the stimulation of hepatic very-low-density lipoprotein-triglyceride (TG) production in vivo. However, only a few studies on the relationship between SNS and hepatic steatosis have been reported. Here, we investigate the effect of adrenergic receptor agonists on hepatic steatosis in mice fed a high-fat diet (HFD). The α-adrenergic receptor agonist phenylephrine (10 mg/kg/d) or the ß-adrenergic receptor agonist isoproterenol (30 mg/kg/d) was coadministered with HFD to male mice. After five weeks, hepatic steatosis, TG levels, and hepatic fat metabolism-related biomarkers were examined. HFD treatment induced hepatic steatosis, and cotreatment with phenylephrine, but not isoproterenol, attenuated this effect. Phenylephrine administration upregulated the mRNA levels of hepatic peroxisome proliferator-activated receptor alpha and its target genes (such as carnitine palmitoyltransferase 1) and increased hepatic ß-hydroxybutyrate levels. Additionally, phenylephrine treatment increased the expression of the autophagosomal marker LC3-II but decreased that of p62, which is selectively degraded during autophagy. These results indicate that phenylephrine inhibits hepatic steatosis through stimulation of ß-oxidation and autophagy in the liver.


Subject(s)
Adrenergic alpha-1 Receptor Agonists/pharmacology , Adrenergic beta-Agonists/pharmacology , Fatty Liver/metabolism , Isoproterenol/pharmacology , Liver/drug effects , Phenylephrine/pharmacology , 3-Hydroxybutyric Acid/metabolism , Animals , Carnitine O-Palmitoyltransferase/genetics , Carnitine O-Palmitoyltransferase/metabolism , Diet, High-Fat/adverse effects , Fatty Liver/etiology , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , PPAR alpha/genetics , PPAR alpha/metabolism , Triglycerides/metabolism
14.
J Cell Sci ; 130(3): 614-625, 2017 02 01.
Article in English | MEDLINE | ID: mdl-27980070

ABSTRACT

Splice variants of certain genes impact on genetic biodiversity in mammals. The tumor suppressor TP53 gene (encoding p53) plays an important role in the regulation of tumorigenesis in hepatocellular carcinoma (HCC). Δ40p53α is a naturally occurring p53 isoform that lacks the N-terminal transactivation domain, yet little is known about the role of Δ40p53α in the development of HCC. Here, we first report on the role of Δ40p53α in HCC cell lines. In the TP53+/Δ40 cell clones, clonogenic activity and cell survival dramatically decreased, whereas the percentage of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells and p21 (also known as WAF1, CIP1 and CDKN1A) expression significantly increased. These observations were clearly attenuated in the TP53+/Δ40 cell clones after Δ40p53α knockdown. In addition, exogenous Δ40p53 expression significantly suppressed cell growth in HCC cells with wild-type TP53, and in those that were mutant or null for TP53 Notably, Δ40p53α-induced tumor suppressor activity was markedly attenuated in cells expressing the hot-spot mutant Δ40p53α-R175H, which lacks the transcription factor activity of p53. Moreover, Δ40p53α expression was associated with increased full-length p53 protein expression. These findings enhance the understanding of the molecular pathogenesis of HCC and show that Δ40p53α acts as an important tumor suppressor in HCC cells.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cellular Senescence , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Tumor Suppressor Protein p53/metabolism , Base Sequence , Cell Proliferation , Clone Cells , G1 Phase Cell Cycle Checkpoints , Gene Deletion , Gene Knockdown Techniques , Hep G2 Cells , Humans , Models, Biological , Mutant Proteins/metabolism , Phenotype , Transcription, Genetic
15.
Endoscopy ; 51(6): 566-570, 2019 06.
Article in English | MEDLINE | ID: mdl-30759466

ABSTRACT

BACKGROUND: Balloon enteroscopy-assisted balloon dilation and temporary biliary stent placement are effective for hepaticojejunostomy anastomotic strictures (HJAS), but the re-stenosis rates are relatively high. We examined the feasibility and efficacy of a novel treatment technique for refractory HJAS, called balloon enteroscopy-assisted radial incision and cutting (BE-RIC). METHODS: Between January 2016 and June 2018, 11 patients with refractory HJAS that recurred after balloon dilation and/or stent placement, underwent BE-RIC. We evaluated the technical success, clinical success, adverse events, and re-stenosis rates associated with BE-RIC. RESULTS: The technical success rate of BE-RIC was 91 % (10/11). Clinical success was achieved in all patients who underwent technically successful procedures. The procedure-related adverse event rate was 9 % (1/11). No re-stenosis was observed during the follow-up period; 9 patients were followed up for more than 6 months, and of these, 5, 4, and 2 patients were followed up for more than 12, 18, and 24 months, respectively, without re-stenosis. CONCLUSIONS: BE-RIC for refractory HJAS showed favorable results. BE-RIC might be a useful option for treating refractory HJAS.


Subject(s)
Biliary Tract Diseases/etiology , Biliary Tract Diseases/surgery , Biliary Tract Surgical Procedures , Postoperative Complications/etiology , Postoperative Complications/surgery , Single-Balloon Enteroscopy , Aged , Aged, 80 and over , Anastomosis, Surgical , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Female , Humans , Male , Middle Aged , Recurrence , Reoperation , Stents
16.
Dig Endosc ; 31(6): 698-705, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31120163

ABSTRACT

BACKGROUND AND AIM: Endoscopic placement of three branched self-expandable metallic stents (SEMS) for high-grade malignant hilar biliary obstruction (MHBO) is technically challenging. We examined the feasibility and efficacy of a novel stenting method combining side-by-side and stent-in-stent (SBSIS) placement for MHBO. METHODS: Between January 2015 and December 2018, 27 consecutive patients with high-grade MHBO underwent SBSIS placement. We evaluated the technical success, functional success, recurrent biliary obstruction (RBO), adverse events other than RBO, and reintervention success rates associated with SBSIS placement. RESULTS: Technical success rate was 85% (23/27). Insertion of the third SEMS failed in four patients, and median diameter of the common bile duct (CBD) was significantly smaller in patients in whom technical failure occurred (5 mm vs 8 mm; P = 0.004). Functional success was achieved in all patients in whom the procedure was a technical success. Rate of adverse events other than RBO was 15% (4/27). RBO rate was 43% (10/23), and median time to RBO was 157 days. Success rate of endoscopic reintervention for RBO was 89% (8/9). CONCLUSION: SBSIS placement showed favorable results and is a promising option in patients with high-grade MHBO requiring triple metal stenting. However, it might be preferable to avoid SBSIS in patients with a narrow CBD. Clinical Trial Registry: UMIN000035721.


Subject(s)
Bile Duct Neoplasms/surgery , Cholangiopancreatography, Endoscopic Retrograde/methods , Cholestasis/surgery , Prosthesis Implantation/methods , Self Expandable Metallic Stents , Sphincterotomy, Endoscopic/methods , Aged , Aged, 80 and over , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/diagnosis , Cholestasis/diagnosis , Cholestasis/etiology , Female , Humans , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
17.
Scand J Gastroenterol ; 53(5): 598-603, 2018 05.
Article in English | MEDLINE | ID: mdl-29183203

ABSTRACT

OBJECTIVE: Biliary forceps biopsies are essential for differentially diagnosing biliary strictures and evaluating the preoperative superficial intraductal spread of bile duct cancers; however, these biopsies are technically demanding and time consuming. Using controllable biopsy-forceps (C-BF), which enable the tip's angle to be adjusted by up to 90°, may facilitate the procedure and improve the diagnostic yield for biliary biopsies. This study aimed to examine the efficacy of C-BF associated with the diagnosis of biliary strictures. MATERIALS AND METHOD: Between 2009 and 2015, 110 patients with biliary strictures underwent biliary biopsies using C-BF. We retrospectively evaluated the diagnostic yield of C-BF for biliary strictures and determined the success rate associated with obtaining adequate samples during mapping biopsies to evaluate the superficial intraductal tumor spread. RESULTS: The technical success rate for biliary biopsies using C-BF was 99% (109/110). The sensitivity, specificity and accuracy of the diagnoses of biliary strictures were 60% (46/77), 100% (33/33) and 72% (79/110), respectively. Regarding the mapping biopsy procedures, adequate samples were successfully obtained from 96% (22/23), 92% (11/12), 80% (12/15), 75% (9/12) and 31% (5/16) of the intrapancreatic common bile ducts, upper common bile ducts, confluences of the hepatic ducts, right intrahepatic bile ducts and left intrahepatic bile ducts, respectively. CONCLUSIONS: C-BF may facilitate biliary cannulation and mapping biopsies of the common bile duct and the right intrahepatic bile duct. However, given that the diagnostic sensitivity was 60%, further modifications are expected and necessary to maximize the utility of the controllable mechanism.


Subject(s)
Bile Duct Neoplasms/diagnosis , Cholestasis/pathology , Constriction, Pathologic/diagnosis , Pancreatic Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/complications , Bile Ducts/pathology , Biopsy , Cholangiocarcinoma/diagnosis , Cholangiopancreatography, Endoscopic Retrograde , Constriction, Pathologic/etiology , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/complications , Retrospective Studies , Sensitivity and Specificity , Surgical Instruments
18.
Hepatol Res ; 47(13): 1417-1428, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28257594

ABSTRACT

AIM: Several studies on the efficacy of ezetimibe, a potent inhibitor of cholesterol absorption, in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been published; however, the results are inconsistent. We undertook a meta-analysis to evaluate the efficacy of ezetimibe in treating NAFLD and NASH. METHODS: PubMed, Medline, and Cochrane Library Full Text Database were searched until June 2016. The main inclusion criteria included original studies investigating the use of ezetimibe for the treatment of NAFLD and NASH. Identification of published work and data extraction were carried out by two reviewers based on the inclusion and exclusion criteria. All analyses were carried out using Comprehensive Meta-Analysis version 3 software. RESULTS: An initial search identified 103 peer-reviewed articles and abstracts. Six studies (two randomized controlled and four single-arm trials) involving 273 participants with NAFLD and NASH were identified. Ezetimibe significantly reduced serum aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase levels, and hepatic steatosis and hepatocyte ballooning. However, hepatic inflammation and fibrosis did not improve by ezetimibe treatment in patients with NAFLD and NASH. In randomized controlled trials, only hepatocyte ballooning improved with ezetimibe treatment. CONCLUSIONS: Although ezetimibe attenuated serum liver enzymes and hepatic steatosis and ballooning in six studies, it improved only hepatocyte ballooning in randomized controlled trials. Larger studies and more randomized placebo-controlled trials are necessary to determine the effects of ezetimibe on NAFLD and NASH.

19.
J Gastroenterol Hepatol ; 32(12): 1922-1930, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28406534

ABSTRACT

BACKGROUND AND AIM: A reliable, non-invasive biomarker for diagnosis of liver fibrosis in chronic liver disease patients is needed. The aim of this study was to assess by meta-analysis the efficacy of measuring serum levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP), a novel and promising biomarker, for staging liver fibrosis and predicting the development of hepatocellular carcinoma and overall survival. METHODS: We performed a meta-analysis using online journal database searches. We identified 39 studies, 21 of which met the criteria for meta-analysis. Sensitivity and specificity of WFA+ -M2BP for assessing liver fibrosis staging in chronic liver diseases with broad etiologies were determined. Hazard ratios with 95% confidence intervals were also used for predicting hepatocellular carcinoma development and overall survival. RESULTS: With WFA+ -M2BP, the sensitivity and specificity for predicting significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and liver cirrhosis (= F4) were 0.690 and 0.778, 0.764 and 0.758, and 0.818 and 0.839, respectively. Sensitivity and specificity for diagnosing liver fibrosis in patients with hepatitis C virus were mostly higher than those in overall patients. However, sensitivity and specificity for diagnosing liver fibrosis in patients with hepatitis B virus were lower than those in overall patients. Overall, hazard ratios for development of hepatocellular carcinoma and overall survival were 5.946 and 1.068, respectively. CONCLUSIONS: These results suggest that serum WFA+ -M2BP is a reliable predictor for liver fibrosis staging and a good substitute for liver biopsy. It is also useful for predicting both hepatocellular carcinoma development and overall survival.


Subject(s)
Antigens, Neoplasm/blood , Liver Cirrhosis/diagnosis , Membrane Glycoproteins/blood , Plant Lectins , Receptors, N-Acetylglucosamine , Biomarkers/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Chronic Disease , Databases, Bibliographic , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Predictive Value of Tests , Prognosis , Sensitivity and Specificity , Survival Rate
20.
Dig Dis Sci ; 62(9): 2542-2549, 2017 09.
Article in English | MEDLINE | ID: mdl-28766242

ABSTRACT

BACKGROUND: Endoscopic bilateral self-expandable metallic stent (SEMS) placement for malignant hilar biliary obstructions (MHBOs) is technically demanding, and a second SEMS insertion is particularly challenging. A simultaneous side-by-side (SBS) placement technique using a thinner delivery system may mitigate these issues. AIMS: We aimed to examine the feasibility and efficacy of simultaneous SBS SEMS placement for treating MHBOs using a novel SEMS that has a 5.7-Fr ultra-thin delivery system. METHODS: Thirty-four patients with MHBOs underwent SBS SEMS placement between 2010 and 2016. We divided the patient cohort into those who underwent sequential (conventional) SBS placement between 2010 and 2014 (sequential group) and those who underwent simultaneous SBS placement between 2015 and 2016 (simultaneous group), and compared the groups with respect to the clinical outcomes. RESULTS: The technical success rates were 71% (12/17) and 100% (17/17) in the sequential and simultaneous groups, respectively, a difference that was significant (P = .045). The median procedure time was significantly shorter in the simultaneous group (22 min) than in the sequential group (52 min) (P = .017). There were no significant group differences in the time to recurrent biliary obstruction (sequential group: 113 days; simultaneous group: 140 days) or other adverse event rates (sequential group: 12%; simultaneous group: 12%). CONCLUSIONS: Simultaneous SBS placement using the novel 5.7-Fr SEMS delivery system may be more straightforward and have a higher success rate compared to that with sequential SBS placement. This new method may be useful for bilateral stenting to treat MHBOs.


Subject(s)
Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/surgery , Klatskin Tumor/diagnostic imaging , Klatskin Tumor/surgery , Prosthesis Design/instrumentation , Stents , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Metals , Retrospective Studies
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