Transpancreatic Sphincterotomy After Double Guidewire Technique Was Noninferior to Primary Transpancreatic Sphincterotomy in Difficult Biliary Cannulation.

BACKGROUND: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. AIMS: Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. METHODS: We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. RESULTS: Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. CONCLUSIONS: The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails.

Indomethacin Does Not Reduce Post-ERCP Pancreatitis in High-Risk Patients Receiving Pancreatic Stenting.

BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.

Suspected drug-induced liver injury associated with iguratimod: a case report and review of the literature.

BACKGROUND: Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy. CASE PRESENTATION: In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren's syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment. CONCLUSIONS: Based on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.

Application of citric acid can enhance the accuracy for 13C-urea breath tests in the diagnosis of Helicobacter pylori infection in Chinese patients.

Previous published data have confirmed that the addition of a citric acid meal improves the accuracy of the 13C-urea breath test (13C-UBT). However, some studies have suggested that a citric acid test meal may not be necessary. Thus, the aim of this study was to evaluate the combination of a 13C-UBT with a citric acid meal for the diagnosis of Helicobacter pylori (Hp) infection in a Chinese population, particularly for patients with results in the gray zone. In this paired self-controlled study, all subjects had previously undergone 13C-UBTs without citric acid meals and were randomly divided into two groups based on different doses of citric acid (a low-dose citric acid group and a high-dose citric acid group, comprising meals with 0.68 g and 3.84 g citric acid powder, respectively). Positive rapid urease test (CLO) test and histology results were considered the 'gold standard'. The mean delta over baseline (DOB) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were compared between the two groups, particularly for patients with results in the gray zone. In total, 285 patients were tested. Of these patients, 189 were included in the low-dose citric acid group, and 96 were included in the high-dose citric acid group. Among patients with a positive 13C-UBT result without citric acid [delta over baseline (DOB) value ≥ 4‰, n = 174] and a negative 13C-UBT result without citric acid (DOB value < 4‰, n = 111), 8.0% (14/174) were false positive, and 0.9% (1/111) was false negative as determined by gold standard. Of 14 patients with false positive, 78.6% (11/14) false positive were in the gray zone of 4-10‰. However, there were no false positive 13C-UBT results with citric acid in the the gray zone of 4-10‰. In the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, NPV and accuracy at 15 min were as follows: 99.1% vs. 99.1%, 97.5% vs. 88.9%, 98.2% vs. 92.2%, 98.8% vs. 98.6% and 98.4% vs. 94.7%, respectively. In the the gray zone of 4.0-10.0‰, the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, and accuracy at 15 min were as follows: 94.4% vs. 100.0%, 100.0% vs. 0%, 100.0% vs. 75.0% and 95.8% vs. 75.0%, respectively. No significant difference was observed between the 15-min and 30-min measurement intervals in the low- and high-dose citric acid groups, including patients with results in the gray zone. The low-dose citric acid test, with an optimal measurement interval of 15 min, was highly accurate in the diagnosis of Hp infection in the Chinese population, especially for individuals with results in the gray zone.

Real-world evidence comparing early and late pancreatic stent placement to prevent post-ERCP pancreatitis.

Background and study aims Pancreatic stenting effectively lowers the occurrence of post-ERCP pancreatitis (PEP) and reduces its severity. However, limited research has been conducted to determine the optimal timing for pancreatic stent placement. Our objective was to evaluate whether early pancreatic stent placement (EPSP) is more effective than late pancreatic stent placement (LPSP) in preventing PEP among patients with naive papilla. Patients and methods We conducted a retrospective cohort study that analyzed 590 patients with difficult biliary cannulation using the pancreatic guidewire technique, who were divided into EPSP and LPSP groups. In the EPSP group, a pancreatic stent was placed immediately before/after endoscopic retrograde cholangiography (ERC) or endoscopic sphincterotomy (EST). Conversely, in the LPSP group, a pancreatic stent was placed after partial/all completion of major endoscopic procedures. Results From November 2017 to May 2023, 385 patients were in the EPSP group and 205 in the LPSP group. EPSP was associated with a decreased PEP occurrence compared with LPSP (2.9% vs. 7.3%; P = 0.012). Similarly, hyperamylasemia was lower in the EPSP group (19.7% vs. 27.8%; P = 0.026). Furthermore, sensitivity analysis using multivariable analysis and propensity score-matched (PSM) analysis also validated these findings. Conclusions Early pancreatic stent placement reduced the incidence of PEP and hyperamylasemia compared with late pancreatic stent placement. Our findings favor pancreatic stenting immediately before/after ERC or EST.

Melatonin Alleviates Liver Fibrosis by Inhibiting Autophagy.

OBJECTIVE: Melatonin has been reported to suppress inflammation and alleviate liver fibrosis, but its effect on autophagy in liver fibrosis has not been studied. This study investigated the effect of melatonin on autophagy in an animal model of liver fibrosis and the hepatic stellate cell (HSC)-T6 cell line. METHODS: The model was established in rats through carbon tetrachloride treatment, and melatonin was administered at three doses (2.5, 5.0, and 10.0 mg/kg). Haematoxylin and eosin staining and Van Gieson's staining were performed to examine the pathological changes of liver. The expression of alpha-smooth muscle actin (α-SMA) and Beclin1 in liver tissues was detected by immunohistochemical staining. The protein levels of α-SMA, Beclin1 and LC3 in the animal model were detected by Western blot analysis, and gene levels of Beclin1 and LC3 were detected by quantitative real-time PCR (qRT-PCR) in the animal model. HSC-T6 cells were activated by platelet-derived growth factor-BB (PDGF-BB). The expression of α-SMA, Beclin1 and collagen I was detected by Western blot analysis, and the gene expression of Beclin1 and LC3 was detected by qRT-PCR. RESULTS: Melatonin reduced the expression of α-SMA, Beclin1 and LC3 in liver tissues. In addition, melatonin inhibited the activation of HSC-T6 cells and the expression of α-SMA, Beclin1 and LC3 in these cells. These results revealed that melatonin could inhibit autophagy and HSC activation. CONCLUSION: Melatonin might ameliorate liver fibrosis by regulating autophagy, suggesting that melatonin is a potential therapeutic agent for liver fibrosis.

Significance of elevated levels of collagen type IV and hyaluronic acid in gastric juice and serum in gastric cancer and precancerous lesion.

BACKGROUND AND AIMS: Collagen type IV and hyaluronic acid (HA) are the major components of basement membrane and extracellular matrix, respectively. Cathepsin D is an aspartyl lysosomal protease involved in the degradation of the basement membrane and extracellular matrix. The aim of this study is to investigate the clinical significance of collagen type IV and hyaluronic acid in gastric juice and serum in diagnosis of gastric cancer and the degrading effect of cathepsin D on collagen type IV and HA. METHODS: Fifty gastric cancer patients were enrolled in our study compared with 41 patients with precancerous lesion and 30 control subjects. Collagen type IV and HA in gastric juice and serum were analyzed by radioimmunoassay. Expression of cathepsin D and collagen type IV in tissue were analyzed by immunohistochemical staining with monoclonal antibodies. RESULTS: The contents of collagen type IV and HA in gastric juice and HA in serum were significantly higher in patients with gastric cancer than those in patients with precancerous lesion and control group (p < 0.05, p < 0.0001). Gastric cancer patients with lymph node metastasis had a higher level of collagen type IV and HA in gastric juice than those in patients without metastasis (p = 0.049, p = 0.043). The expression of cathepsin D had significantly increased in patients with gastric cancer compared to the control group (p < 0.0001). The continuous expression of collagen type IV in basement membrane in gastric cancer group was lower than that in the precancerous lesion group and control group (p < 0.0001). CONCLUSIONS: The analysis of collagen type IV and HA in gastric juice and serum may provide a simple aid in diagnosing gastric cancer and evaluating whether metastasis is occurring or not.

Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-ß1/Smad Signaling Pathway.

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect. Nevertheless, the mechanism is not completely identified. This study was conducted to investigate the effects of melatonin on TGF-ß1/Smad signaling pathway in liver fibrosis in rats. The liver fibrosis model was made by the subcutaneous injection of CCl4. The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer. Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry. Expression levels of TGF-ß1, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis. Results showed that melatonin suppressed CCl4-induced liver fibrosis, along with an improvement in histological changes, significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver. Melatonin improved liver function indicated by decreased serum ALT and AST activities. In addition, melatonin exerted its anti-oxidant effects, as supported by decreased MDA levels and increased GPx activities in liver. Furthermore, melatonin inhibited TGF-ß1/Smad pathway, as evidenced by decreased TGF-ß1, Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver. In conclusion, melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-ß1/Smad pathway. It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

Silymarin's Protective Effects and Possible Mechanisms on Alcoholic Fatty Liver for Rats.

Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-κB (NF-κB), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-κB p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-κB.

Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats.

AIM: To investigate the protective effects of melatonin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats. METHODS: All rats were randomly divided into normal control group, model control group treated with CCl4 for 12 wk, CCl4 + NAC group treated with CCl4 + NAC (100 mg/kg, i.p.) for 12 wk, CCl4 + MEL-1 group treated with CCl4 + melatonin (2.5 mg/kg) for 12 wk, CCl4 + MEL-2 group treated with CCl4 + melatonin (5.0 mg/kg) for 12 wk, and CCl4 + MEL-3 group treated with CCl4 + melatonin (10 mg/kg). Rats in the treatment groups were injected subcutaneously with sterile CCl4 (3 mL/kg, body weight) in a ratio of 2:3 with olive oil twice a week. Rats in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment groups. At the end of experiment, rats in each group were anesthetized and sacrificed. Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine changes in liver pathology. Serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and protein concentration were measured with routine laboratory methods using an autoanalyzer. Hydroxyproline (HYP) content in liver and malondialdehyde (MDA) and glutathione peroxidase (GPx) levels in liver homogenates were assayed by spectrophotometry. Serum hyaluronic acid (HA), laminin (LN), and procollagen III N-terminal peptide (PIIINP) were determined by radioimmunoassay. RESULTS: Pathologic grading showed that the fibrogenesis was much less severe in CCl4 + MEL3 group than in model control group (u = 2.172, P < 0.05), indicating that melatonin (10 mg/kg) can significantly ameliorate CCl4-induced hepatic fibrotic changes. The serum levels of ALT and AST were markedly lower in CCl4 + MEL treatment groups (5, 10 mg/kg) than in model control group (ALT: 286.23 +/- 121.91 U/L vs 201.15 +/- 101.16 U/L and 178.67 +/- 103.14 U/L, P = 0.028, P = 0.007; AST: 431.00 +/- 166.35 U/L vs 321.23 +/- 162.48 U/L and 292.42 +/- 126.23 U/L, P = 0.043, P = 0.013). Similarly, the serum laminin (LN) and hyaluronic acid (HA) levels and hydroxyproline (HYP) contents in liver were significantly lower in CCl4 + MEL-3 group (10 mg/kg) than in model control group (LN: 45.89 +/- 11.71 microg/L vs 55.26 +/- 12.30 microg/L, P = 0.012; HA: 135.71 +/- 76.03 microg/L vs 201.10 +/- 68.46 microg/L, P = 0.020; HYP: 0.42 +/- 0.08 mg/g tissue vs 0.51 +/- 0.07 mg/g tissue, P = 0.012). Moreover, treatment with melatonin (5, 10 mg/kg) significantly reduced the MDA content and increased the GPx activity in liver homogenates compared with model control group (MDA: 7.89 +/- 1.49 noml/mg prot vs 6.29 +/- 1.42 noml/mg prot and 6.25 +/- 2.27 noml/mg prot, respectively, P = 0.015, P = 0.015; GPx: 49.13 +/- 8.72 U/mg prot vs 57.38 +/- 7.65 U/mg prot and 61.39 +/- 13.15 U/mg prot, respectively, P = 0.035, P = 0.003). CONCLUSION: Melatonin can ameliorate CCl4-induced hepatic fibrosis in rats. The protective effect of melatonin on hepatic fibrosis may be related to its antioxidant activities.