Apoptosis and non-alcoholic fatty liver diseases Kanda, Tatsuo; Matsuoka, Shunichi; Yamazaki, Motomi ...
World journal of gastroenterology,
2018-Jul-07, 2018-7-7, 20180707, Volume:
24, Issue:
25
Journal Article
Open access
The number of patients with nonalcoholic fatty liver diseases (NAFLD) including nonalcoholic steatohepatitis (NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma (HCC) and ...is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.
Background and Aims
Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are ...experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS‐FNA procedure used for histopathologic diagnoses.
Methods
A retrospective analysis of cases with EUS‐FNA‐related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis.
Results
Of the 13,566 EUS‐FNA cases overall, the total number of cases in which adverse events related to EUS‐FNA occurred was 234. The incidence of EUS‐FNA‐related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS‐FNA was observed during the follow‐up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS‐FNA.
Conclusions
This study revealed that the adverse events‐related EUS‐FNA for histopathologic diagnoses were not severe conditions, and had low incidence.
The Asian Federation of Societies for Ultrasound in Medicine and Biology aimed to provide information on techniques and indications for contrast-enhanced harmonic endoscopic ultrasound (CH-EUS), and ...to create statements including the level of recommendation. These statements are based on current scientific evidence reviewed by a Consensus Panel of 15 internationally renowned experts. The reliability of clinical questions was measured by agreement rates after voting. Six statements were made on techniques, including suitable contrast agents for CH-EUS, differences between contrast agents, setting of mechanical index, dual imaging and duration and phases for observation. Thirteen statements were made on indications, including pancreatic solid masses, pancreatic cancer staging, pancreatic cystic lesions and mural nodules, detection of subtle pancreatic lesions, gallbladder sludge and polyps, hepatic lesions, lymph nodes, subepithelial lesions, visceral vascular diseases, guidance of fine needle aspiration and evaluation for local therapy. These international expert consensus guidelines will assist endosonographers in conducting CH-EUS according to evidence-based information.
Background Pancreatic necrosis and pancreatic abscess are severe complications of acute pancreatitis. Surgery is associated with significant morbidity and mortality in these critically ill patients. ...Endoscopic therapy has the potential to offer a safer and more effective alternative treatment modality. However, its role needs to be further investigated. Methods This is a retrospective study of the outcome of consecutive patients with pancreatic necrosis and pancreatic abscess, all unfit to undergo surgery, who underwent a new aggressive endoscopic approach. The treatment includes (1) synchronous EUS-guided multiple transmural and/or transpapillary drainage procedures followed by balloon dilation of the cystogastrostoma or cystoduodenostoma, (2) daily endoscopic necrosectomy and saline solution lavage, and (3) sealing of pancreatic fistula by N-butyl-2-cyanoacrylate. Results Pancreatic necrosis and pancreatic abscesses were successfully drained in 13 patients, thus avoiding emergency surgery as an initial treatment. Surgery was completely avoided in 9 patients over a median follow-up of 8.3 months (range 3-81 months). Surgery was combined with endoscopic therapy in one patient because of abscess extension into the right paracolic gutter, which was not manageable by endoscopic drainage. Because of the “dislocated-duct syndrome,” two patients later developed recurrent pseudocysts and underwent elective surgery. Complications included minor bleeding after balloon dilation and necrosectomy in 4 cases, which were self limiting or controlled endoscopically. Conclusions This aggressive endoscopic approach shows promising results. It expands the potential for endoscopic treatment in patients with pancreatic necrosis and/or pancreatic abscess.
Purpose
No studies of the relationship between grayscale sonographic findings and pancreatic fat content have been reported to date. This study aimed to investigate the correlation between ...echogenicity and fat content of resected specimens using quantitative analysis.
Methods
Forty-two consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy for pancreatic tumors were enrolled in this study. Ultrasonographic images were compared with quantitative pathological analysis. Subjective evaluation of echogenicity was classified as hypoechoic, isoechoic, hyperechoic, and super hyperechoic. The total and intralobular fat areas were measured.
Results
The mean, median, modal, minimum, and maximum ultrasound gray values correlated with the proportion of total fat area (r = 0.349; 0.357, 0.486, 0.466, and 0.347
; p
= 0.024, 0.020, 0.014, 0.019, and 0.089, respectively), but did not correlate with the proportion of intralobular fat area. Subjective classification was correlated with median gray value (
p
< 0.001), intralobular fat area (
p
= 0.118), and total fat area (
p
= 0.011). Cases were classified as hypoechoic (n = 3), isoechoic (n = 7), hyperechoic (n = 30), and super hyperechoic (n = 2). The subjective classification was correlated with the median gray value (
p
< 0.001) and total fat area (
p
= 0.005), and not correlated with the intralobular fat area (
p
= 0.118). Hyperechoic or super hyperechoic pancreatic parenchyma contains over 19.7% fat. Computed tomography values correlated with the proportion of intralobular fat area (r = − 0.479, p = 0.004) and total fat area (r = − 0.541, p < 0.001).
Conclusion
Echogenicity classified based on subjective evaluation and image analysis were correlated with the proportion of fat in the pancreas.
Ultrasound-targeted microbubble destruction (UTMD) induces cellular inflow of drugs at low intensity, while high intensity eradicates tumor vessels. Since vascular endothelial growth factor receptor ...2 (VEGFR2) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), VEGFR2-targeted microbubble (MB) might additionally increase the tissue specificity of drugs and thus improve antitumor effects. In addition, fixing the dual pulse intensity could maximize MB properties. This study evaluated the one-off (experiment 1) and cumulative (experiment 2) treatment effect of UTMD by regulating the dual pulse output applied to PDAC using VEGFR2-targeted MB.
C57BL/6 mice inoculated with Pan-02 cells were allocated to five groups: VEGFR2-targeted MB+ gemcitabine (GEM), VEGFR2-targeted MB, non-targeted MB+GEM, GEM, and control groups. After injection of GEM or GEM and either VEGFR2-targeted or non-targeted MB, UTMD was applied for several minutes at low intensity followed by high intensity application. In experiment 1, mice were treated by the protocol described above and then euthanized immediately or at the tumor diameter doubling time (TDT). In experiment 2, the same protocol was repeated weekly and mice were euthanized at TDT regardless of protocol completion. Histological analysis by CD31 and VEGFR2 staining provided microvascular density (MVD) and VEGFR2 expression along vessels (VEGFR2v) or intra/peripheral cells (VEGFR2c).
In experiment 1, TDT was significantly longer in the VEGFR2-targeted MB+GEM group compared to the non-targeted MB+GEM, GEM, and control groups, while the VEGFR2-targeted MB group showed no statistical significance. MVD and VEGFR2v in the immediate euthanasia was significantly lower in the VEGFR2-targeted MB+GEM and VEGFR2-targeted MB groups than other conditions. In experiment 2, the VEGFR2-targeted MB+GEM group produced significantly longer TDT than the GEM or control groups, whereas the VEGFR2-targeted MB group showed no significant difference. Histology revealed significantly reduced VEGFR2v and VEGFR2c in the VEGFR2-targeted and non-targeted MB+GEM groups, while only VEGFR2v was significantly less in the VEGFR2-targeted MB group.
UTMD-mediated GEM therapy with the dual pulse application using VEGFR2-targeted MB substantially suppresses PDCA growth.
Background and Aims
Differentiation of gallbladder (GB) carcinoma from benign GB wall thickening is challenging. The recent introduction of second-generation ultrasonic contrast agents has made ...contrast harmonic imaging with EUS possible. The aim of our study was to evaluate the utility of contrast-enhanced harmonic EUS (CH-EUS) for the differential diagnosis of GB wall thickening.
Methods
Thirty-six consecutive patients with GB wall thickening imaged by CH-EUS and then underwent surgery were enrolled in this study. After the lesions were observed with conventional harmonic EUS (H-EUS), CH-EUS was performed with intravenous injection of 0.015 ml/kg of Sonazoid. Three reviewers with various levels of experience of EUS (Reviewer A: experienced endosonographer, B: EUS trainee, C: experienced gastroenterologist with expertise in transabdominal ultrasound but no EUS experience) were blinded to findings of recorded video of H-EUS and CH-EUS. The diagnostic accuracy of H-EUS and CH-EUS for malignant GB wall thickening was compared.
Results
Final diagnoses based on surgical histology were GB carcinoma in 16, cholecystitis in 11, adenomyomatosis in 6 and cholesterolosis in 3. Overall sensitivity, specificity and accuracy for diagnosing malignant GB wall thickening of H-EUS and CH-EUS were 83.3 versus 89.6, 65 versus 98 % (
p
< 0.001) and 73.1 versus 94.4 % (
p
< 0.001). The inter-observer agreement for H-EUS was moderate (
κ
= 0.51), whereas that for CH-EUS was substantial (
κ
= 0.77). The inhomogeneous enhanced pattern on CH-EUS was a strong predictive factor of malignant GB wall thickening.
Conclusion
CH-EUS has the potential to improve the preoperative diagnostic accuracy and inter-observer agreement in the differential diagnosis of GB wall thickening.
Background/Aims
The sensitivities of endoscopic trans‐papillary pathologic diagnosis of biliary tract cancer (BTC) are unsatisfactory. Recently, the diagnostic utility of the endoscopic scraper ...device, Trefle for biliary stricture has been reported. The Trefle can be guided to the target biliary stricture over the guidewire and is as easy to use as the conventional brush catheter (CBC). This study evaluated the efficacy and safety of Trefle‐assisted tissue acquisition combined cell block method and CBC cytology for biliary strictures due to BTCs.
Methods
We retrospectively reviewed consecutive patients with biliary strictures in whom CBC cytology or Trefle‐assisted tissue acquisition under endoscopic retrograde cholangiopancreatography was performed for suspected BTCs from January 2015 to June 2022 at our institution.
Results
173 patients (CBC group; n = 55, Trefle group; n = 118) were enrolled in this study. The sensitivity, specificity, and accuracy of CBC cytology for BTC were 68.3%/100%/76.4%. On the other hand, the sensitivity, specificity, and accuracy of Trefle‐assisted tissue acquisition for BTC were 93.7%/95.7%/94.1%, showing superior sensitivity (p < 0.001) and accuracy (p = 0.002) compared to that of CBC.
Conclusions
Compared to CBC cytology, Trefle‐assisted tissue acquisition has superior diagnostic performance while maintaining procedural simplicity and is considered useful for diagnosing malignant biliary stricture.
Introduction. Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is a useful therapeutic procedure that provides promising results in patients with surgically ...altered anatomy. However, biliary cannulation in BE-ERCP remains challenging. Therefore, in patients with Roux-en-Y gastrectomy, this study aimed to evaluate a BE-ERCP cannulation strategy that includes the newly developed alpha-retroflex scope position. Methods. This was a retrospective review of 52 patients with Roux-en-Y gastrectomy who underwent BE-ERCP at two centers between April 2017 and December 2022. In these patients, three types of scope position had been used for biliary cannulation: straight (S-position), J-retroflex (J-position), and alpha-retroflex (A-position). First, the S-position was used for biliary cannulation. Then, if biliary cannulation was difficult with this position, the J-position was used, followed by the A-position, if necessary. Results. The biliary cannulation success rate was 96.6% (50/52). The S-, J-, and A-positions achieved successful biliary cannulation in 24 (48%), 14 (28%), and 12 patients (24%), respectively. No adverse events, including post-ERCP pancreatitis and perforation, occurred. Conclusion. This was the first study of a cannulation strategy that included the A-position in addition to the S- and J-positions. The study showed that the A-position is feasible and safe in BE-ERCP in patients with Roux-en-Y gastrectomy.
Background Previous animal studies and a pilot clinical trial demonstrated that submucosal injection of a thiol compound called mesna could chemically soften connective tissues and thus facilitate ...endoscopic submucosal dissection (ESD). Objective To evaluate whether mesna injection could reduce procedural times for gastric ESD. Design Double-blind, block-randomized, controlled trial. Setting University hospital. Patients A total of 101 patients with superficial gastric cancer indicated for ESD were enrolled and randomly assigned to either the mesna or control (saline solution) group. Intervention Traditional ESD was performed with a single bolus injection of mesna or saline solution. Main Outcome Measurements Time for submucosal dissection (TSD). Results En bloc resection was achieved for all lesions in the mesna group (53/53) and 51 of 52 lesions (98.08%) in the control group. TSD was not statistically different between the groups (18.62 ± 13.9 mean ± SD minutes for the mesna group and 24.58 ± 24.55 mean ± SD minutes for the control group; P = .128), and there were fewer time-consuming cases (times over 30 minutes) in the mesna group compared with controls (7/53 vs 15/52; P = .049). Multivariate regression analysis demonstrated that use of mesna, specimen size, and the presence of fibrous scars were significantly correlated with TSD ( P < .05). Limitations Single-center study. Conclusion TSD was not significantly different between the mesna and control injection groups, but multivariate analysis indicated that mesna injection reduced procedural challenges associated with the submucosal dissection. (Clinical trial registration number: UMIN000003786.)
PDF
