Therapeutic outcomes of early and delayed endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangial drainage in patients with obstructive severe acute biliary pancreatitis.

Background: Obstructive severe acute biliary pancreatitis (SABP) is a clinical emergency with a high rate of mortality that can be alleviated by endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangial drainage (PTCD) selectively. However, the optimal timing of ERCP and PTCD requires elucidation. Aim: The aim of this study was to evaluate outcome parameters in patients with SABP subjected to ERCP and PTCD compared to SABP patients who were not subjected to any form of invasive intervention. Methods: A total of 62 patients with obstructive SABP who had been treated from July 2013 to July 2019 were included in this retrospective case-control study and stratified into a PTCD group (N = 22), ERCP group (N = 24), and conservative treatment group (N = 16, control). Patients in the PTCD and ERCP groups were substratified into early (≤72 h) and delayed (>72 h) treatment groups based on the timing of the intervention after diagnosis. Clinical chemistry, hospitalization days, liver function, abdominal pain, and complications were determined to assess the treatment efficacy and safety of each modality and to establish the optimal timing for PTCD and ERCP. Results: The average hospitalization time, time to abdominal pain relief, and time to normalization of hematological and clinical chemistry parameters (leukocyte count, amylase, alanine transaminase [ALT], and total bilirubin [TBiL]) were shorter in the PTCD and ERCP groups compared to the conservative treatment group (p < 0.05). The average hospitalization time in the ERCP group (16.7 ± 4.0 d) was shorter compared to the PTCD group (19.6 ± 4.3 d) (p < 0.05). Compared to the conservative treatment group (62.5%), there were more complications in patients treated with ERCP and PTCD (p < 0.05). In the early ERCP group, the average hospitalization time (13.9 ± 3.3 d) and the time to normalization of leukocyte count (6.3 ± 0.9 d) and TBiL (9.1 ± 2.0 d) were lower than in the delayed ERCP group (18.6 ± 4.1 d, 9.9 ± 2.4 d, 11.8 ± 2.9 d, respectively) and early PTCD group (16.4 ± 3.7 d, 8.5 ± 2.1 d, 10.9 ± 3.1 d, respectively) (p < 0.05). In the delayed ERCP group, the average hospitalization time (18.6 ± 4.1 d) and ALT recovery time (12.2 ± 2.6 d) were lower than in the delayed PTCD group (21.9 ± 4.3 d and 14.9 ± 3.9 d, respectively) (p < 0.05). Conclusions: ERCP and PTCD effectively relieve SABP-associated biliary obstruction with comparable overall incidence of complications. It is recommended that ERCP is performed within 72 h after diagnosis; and PTCD drainage may be considered an alternative approach in cases where patients are unable or unwilling to undergo ERCP, or when ERCP is unsuccessful. Relevance for Patients: ERCP and PTCD in patients with obstructive SABP can resolve biliary obstruction and delay progression of the disease. Performing ERCP and PTCD within 72 h (i.e., optimal treatment time window) can be beneficial to patients, especially in terms of post-operative recovery. Visual biliary endoscopy (oral or percutaneous transhepatic) may be used for concomitant therapeutic interventions in the biliary system.

Cellular senescence: a promising therapeutic target in colorectal cancer.

Colorectal cancer is one of the most malignant cancers worldwide, and efforts have been made to elucidate the mechanism of colorectal carcinogenesis. Cellular senescence is a physiological process in cell life, but it is also found in cancer initiation and progression. Lines of evidence show that senescence may influence the development and progression of colorectal carcinogenesis. Here, the authors review the characteristics of senescence and the recent findings of a relationship between senescence and colorectal cancer.

Cancer is a leading cause of death worldwide; out of the top ten most common cancers in 2020, the incidence and mortality rate of colorectal cancer (CRC) ranked third and second, respectively. Based on statistics, it was estimated that more than 1.9 million CRC cases occurred in 2020. In terms of CRC, a prominent risk factor is age, and studies suggest that the aging process plays a role in CRC initiation and progression. This review discusses how aging contributes to CRC carcinogenesis and summarizes recent findings on potential therapeutics.

Effect of BRMS1 expression on proliferation, migration and adhesion of mouse forestomach carcinoma.

OBJECTIVE: To discuss the effect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma. METHODS: The constructed pCMV-myc-BRMS1 recombinant plasmid and blank plasmid were transfected into mouse forestomach carcinoma. MTT method was employed to measure the activity of gastric cancer cell; the scratch assay and Transwell assay to measure the migration and invasion of gastric cancer cell; the adhesion assay to measure the adhesion of gastric cancer cell; while the Western blot assay to measure the expression of The NF-κB signal pathway, downstream matrix metalloproteinase (MMP)-2, MMP-9 and osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted animal model of gastric cancer in mice was constructed to measure the size of tumor xenograft. RESULTS: Results of MTT assay showed that, compared with the empty vector control group, the activity of gastric cancer cell was not affected in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit the adhesion, migration and invasion of gastric cancer cell (P < 0.01). Besides, compared with the empty vector control group, the phosphorylation of NF-κB p65 and IκBα was reduced in the BRMS1 transfection group, with the decreased expression of MMP-2, MMP-9 and osteopontin and the increased expression of E-cadherin (P < 0.01). Results of animal experiment also showed that the expression of BRMS1 did not affect the transplanted tumor. CONCLUSIONS: The expression of BRMS1 can significantly inhibit the adhesion, migration, invasion and metastasis of mouse forestomach carcinoma gastric cancer cell, which is related to The NF-κB signal pathway.

Melatonin inhibits the expression of vascular endothelial growth factor in pancreatic cancer cells.

OBJECTIVE: To investigate the effects of melatonin on cellular proliferation and endogenous vascular endothelial growth factor (VEGF) expression in pancreatic carcinoma cells (PANC-1). METHODS: PANC-1 cells were cultured for this study. The secreted VEGF concentration in the culture medium was determined using ELISA method, VEGF production in the tumor cells was detected by immunocytochemistry, and VEGF mRNA expression was determined by RT-PCR. RESULTS: Higher melatonin concentrations significantly inhibited cellular proliferation, with 1 mmol/L concentration exhibiting the highest inhibitory effect (P<0.01). VEGF concentrations in the cell culture supernatants and intra-cellules were all significantly reduced after melatonin (1 mmol/L) incubation (P<0.05). VEGF mRNA expression decreased markedly in a time-dependent manner during the observation period (P<0.05). CONCLUSIONS: High melatonin concentrations markedly inhibited the proliferation of pancreatic carcinoma cells. The endogenous VEGF expression was also suppressed by melatonin incubation.

Gastroesophageal reflux in cirrhotic patients without esophageal varices.

AIM: To evaluate the esophageal motility and abnormal acid and bile reflux incidence in cirrhotic patients without esophageal varices (EV). METHODS: Seventy-eight patients with liver cirrhosis without EV confirmed by upper gastroesophageal endoscopy and 30 healthy control volunteers were prospectively enrolled in this study. All the patients were evaluated using a modified protocol including Child-Pugh score, upper gastrointestinal endoscopy, esophageal manometry, simultaneous ambulatory 24-h esophageal pH and bilirubin monitoring. All the patients and volunteers accepted the manometric study. RESULTS: In the liver cirrhosis group, lower esophageal sphincter pressure (LESP, 15.32 ± 2.91 mmHg), peristaltic amplitude (PA, 61.41 ± 10.52 mmHg), peristaltic duration (PD, 5.32 ± 1.22 s), and peristaltic velocity (PV, 5.22 ± 1.11 cm/s) were all significantly abnormal in comparison with those in the control group (P < 0.05), and LESP was negatively correlated with Child-Pugh score. The incidence of reflux esophagitis (RE) and pathologic reflux was 37.18% and 55.13%, respectively (vs. control, P < 0.05). And the incidence of isolated abnormal acid reflux, bile reflux and mixed reflux was 12.82%, 14.10% and 28.21% in patients with liver cirrhosis without EV. CONCLUSION: Cirrhotic patients without EV presented esophageal motor disorders and mixed acid and bile reflux was the main pattern; the cirrhosis itself was an important causative factor.

[Effect of esomeprazole upon intestinal mucosal damage following traumatic brain injury in rats].

OBJECTIVE: To explore the protective effect of esomeprazole upon stress-related intestinal mucosal damage following traumatic brain injury (TBI) in rats. METHODS: Male Wistar rats were randomly divided into three groups: groups A and B served as TBI models and group C was designated as a normal control (shame operation). In group B rats were treated subcutaneously with esomeprazole prior to TBI while groups A and C rats were treated with an equivalent amount of normal saline. During the observation period, the morphological changes of brain tissue and intestinal mucosa were observed. And the intestinal mucosal permeability to fluorescein isothiocyanate (FITC)-labeled dextran and diamine oxidase (DAO) activity were assessed. The activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and the levels of malondialdehyde (MDA), reduced glutathione (GSH) and hydroxyl radical (OH(*)) were measured. RESULTS: (1) During the observation period of TBI, the intestinal mucosal was damaged, but there was improvement in group PPI. (2) FITC-dextran leakage increased after TBI and peaked at 24 h (P < 0.01); its level of (3720 +/- 401) ng/ml in group PPI was lower than that in group TBI (5230 +/- 489) ng/ml (P < 0.05). (3) The DAO activity in mucosa decreased and the decline was the greatest at 24 h (P < 0.05), its level of (0.44 +/- 0.11) ng/ml in group PPI at 24 h was higher than that in group TBI (0.31 +/- 0.07) ng/ml (P < 0.05); while the DAO activity in serum increased significantly. (4) The activity of SOD and the level of GSH in intestinal mucosal started to decrease at 3 h and the decline was the greatest at 24 h (P < 0.05), their levels were (10.2 +/- 2.8) U/mgprot and (140 +/- 46) mg/gprot respectively in group TBI, a remarkable drop in comparison with those of PPI group (13.0 +/- 2.4) U/mgprot and (208 +/- 48) U/gprot (P < 0.05). (5) The levels of OH(.), MDA and MPO in intestinal mucosal increased and peaked at 24 h (P < 0.05), the respective levels in group PPI (108 +/- 8), (6.2 +/- 0.6) and (1.53 +/- 0.52) U/mgprot and those in the TBI group (150 +/- 8), (7.7 +/- 0.9), (1.93 +/- 0.53) U/mgprot, demonstrated that there was a remarkable rise (P < 0.05). CONCLUSION: Traumatic brain injury may lead to stress-related intestinal mucosal damage. Oxygen free radicals play an important role in intestinal mucosal barrier damage. Esomeprazole attenuates the damage of intestinal mucosal barrier by antioxidant effect and inhibiting the activity of neutrophil.