Choledocholithiasis characteristics with periampullary diverticulum and endoscopic retrograde cholangiopancreatography procedures:Comparison between two centers from Lanzhou and Kyoto

BACKGROUND Most of study regarding periampullary diverticulum(PAD)impact on endoscopic retrograde cholangiopancreatography(ERCP)therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients.AIM To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD.METHODS Patients seen in two endoscopy centers(The First Hospital of Lanzhou University,Lanzhou,Gansu Province,China,and Kyoto Second Red Cross Hospital,Kyoto,Japan)underwent ERCP treatment for the first time between January 2012 and December 2017.The characteristics of choledocholithiasis with PAD were compared between the two centers,and their ERCP procedures and therapeutic outcomes were analyzed.RESULTS A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD.Lots of clinical characteristics were significantly different between the two centers.The common bile duct(CBD)diameter was wider,choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients(14.8±5.2 mm vs 11.6±4.2 mm,12.2±6.5 mm vs 8.2±5.3 mm,45.3%vs 20.3%,P<0.001 for all).In addition,concomitant diseases,such as acute cholangitis,gallbladder stones,obstructive jaundice,cholecystectomy,and acute pancreatitis,were significantly different between the two centers(P=0.03 to<0.001).In the Lanzhou center,CBD diameter and choledocholithiasis size were lower,and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients(13.4±5.1 mm vs 14.8±5.2 mm,10.3±5.4 mm vs 12.2±6.5,39%vs 45.3%,13.9%vs 18.5%,P=0.002 to<0.001).But all these characteristics were not significantly different in the Kyoto center.The proportions of endoscopic sphincterotomy(EST),endoscopic balloon dilatation(EPBD),and EST+EPBD were 50.5%,1.7%,and 42.5%in the Lanzhou center and 90.0%,0.0%,and 0.4%in the Kyoto center,respectively.However,the overall post-ERCP complication rate was not significantly different between the two centers(8.9%in the Lanzhou and 5.8%in the Kyoto.P=0.12).In the Lanzhou center,the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group(35.3%vs 26.0%,P<0.001).But the rate was no significant difference between the two groups in Kyoto center.The residual rates of choledocholithiasis were not significantly different between the two groups in both centers.Post-ERCP complications occurred in 8.9%of the PAD patients and 8.1%of the non-PAD patients in the Lanzhou Center,and it occurred in 5.8%in PAD patients and 10.0%in non-PAD patients in the Kyoto center,all P>0.05.CONCLUSION Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers.The patients had larger and multiple stones,wider CBD diameter,and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center.The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers.The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center.

Establishment and characterization of a new human ampullary carcinoma cell line,DPC-X1

BACKGROUND An in-depth study of the pathogenesis and biological characteristics of ampullary carcinoma is necessary to identify appropriate treatment strategies. To date, only eight ampullary cancer cell lines have been reported, and a mixed-type ampullary carcinoma cell line has not yet been reported.AIM To establish a stable mixed-type ampullary carcinoma cell line originating from Chinese.METHODS Fresh ampullary cancer tissue samples were used for primary culture and subculture. The cell line was evaluated by cell proliferation assays, clonal formation assays, karyotype analysis, short tandem repeat(STR) analysis and transmission electron microscopy. Drug resistances against oxaliplatin, paclitaxel, gemcitabine and 5-FU were evaluated by cell counting kit-8 assay. Subcutaneous injection 1 × 106 cells to three BALB/c nude mice for xenograft studies. The hematoxylin-eosin staining was used to detect the pathological status of the cell line. The expression of biomarkers cytokeratin 7(CK7), cytokeratin 20(CK20), cytokeratin low molecular weight(CKL), Ki67 and carcinoembryonic antigen(CEA) were determined by immunocytochemistry assay.RESULTS DPC-X1 was continuously cultivated for over a year and stably passaged for more than 80 generations;its population doubling time was 48 h. STR analysis demonstrated that the characteristics of DPC-X1 were highly consistent with those of the patient’s primary tumor. Furthermore, karyotype analysis revealed its abnormal sub-tetraploid karyotype. DPC-X1 could efficiently form organoids in suspension culture. Under the transmission electron microscope, microvilli and pseudopods were observed on the cell surface, and desmosomes were visible between the cells. DPC-X1 cells inoculated into BALB/C nude mice quickly formed transplanted tumors, with a tumor formation rate of 100%. Their pathological characteristics were similar to those of the primary tumor. Moreover, DPC-X1 was sensitive to oxaliplatin and paclitaxel and resistant to gemcitabine and 5-FU. Immunohistochemistry showed that the DPC-X1 cells were strongly positive for CK7, CK20, and CKL;the Ki67 was 50%, and CEA was focally expressed.CONCLUSION Here, we have constructed a mixed-type ampullary carcinoma cell line that can be used as an effective model for studying the pathogenesis of ampullary carcinoma and drug development.

内镜逆行胰胆管造影术在肝包虫病胆道并发症治疗中的应用

目的探讨内镜逆行胰胆管造影术(ERCP)在肝包虫胆道并发症治疗中的价值。方法回顾分析该院2010年10月-2016年10月ERCP参与治疗的肝包虫病27例,总结患者的临床表现、实验室检验、影像学检查、手术方式及治疗效果。结果该组有27例应用ERCP参与治疗的肝包虫胆道并发症病例。其中,12例因肝包虫囊肿破入胆道引起急性化脓性胆管炎及梗阻性黄疸,7例因肝包虫囊肿压迫胆总管引起重度黄疸,先行ERCP通畅胆道引流,择期行开腹手术;6例因肝包虫内囊摘除术后残腔胆瘘,2例因肝包虫术后胆道狭窄,术后行ERCP放置胆道支架,该组27例均取得良好的治疗效果;比较患者术前24 h内与术后48 h白细胞计数(WBC)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBIL)、碱性磷酸酶(ALP)和γ-转肽酶(GGT)6项指标,术后均有改善,差异有统计学意义(P<0.05)。结论对于肝包虫病引起的急性化脓性胆管炎、胆瘘和胆道狭窄等胆道并发症,在术前或术后采用ERCP处理具有重要的诊治价值。

Pathogenesis of liver cirrhosis

Liver cirrhosis is the final pathological result of various chronic liver diseases,and fibrosis is the precursor of cirrhosis.Many types of cells,cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis.Activation of hepatic stellate cells(HSCs)is a pivotal event in fibrosis.Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis.Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs.Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis.At the molecular level,many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis.Recently,miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis.Robust animal models of liver fibrosis and cirrhosis,as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer

BACKGROUND Early gastric cancer(EGC), compared with advanced gastric cancer(AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method.AIM To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs(miRNAs) in EGC and AGC and compared them with those in benign gastritis(BG).METHODSWe examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori(H. pylori)-negative gastritis(Control-1), and H. pylori-positive atrophic gastritis(Control-2).To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups.RESULTS Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis(Control-1) and H. pyloripositive atrophic gastritis(Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs,miR-7641, miR-425-5 p, miR-1180-3 p and miR-122-5 p, were used to effectively distinguish the Cancer group(EGC + AGC) from the Control group [area under the curve(AUC) = 0.799, 95% confidence interval(CI): 0.691-0.908, P < 0.001].Additionally, miR-425-5 p, miR-24-3 p, miR-1180-3 p and miR-122-5 p were utilized to distinguish EGC from the Control group(AUC = 0.829, 95%CI: 0.657-1.000, P =0.001). Moreover, the miR-24-3 p expression level in EGC was lower than that in the AGC(AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5 p expression level in EGC was significantly higher than that in AGC(AUC = 0.791,95%CI: 0.574-1.000, P = 0.024).CONCLUSION The differentially expressed circulatory plasma miR-425-5 p, miR-1180-3 p, miR-122-5 p, miR-24-3 p and miR-4632-5 p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.

Clinical significance of different periampullary diverticulum classifications for endoscopic retrograde cholangiopancreatography cannulation

BACKGROUND Different types of periampullary diverticulum(PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography(ERCP) cannulation,but the clinical significance of the two current PAD classifications for cannulation is limited.AIM To verify the clinical value of our newly proposed PAD classification.METHODS A new PAD classification(Li-Tanaka classification) was proposed at our center.All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared.RESULTS A total of 3564 patients with native papillae were enrolled, including 967(27.13%)PAD patients and 2597(72.87%) non-PAD patients. In the Li-Tanaka classification, type Ⅰ PAD patients exhibited the highest difficult cannulation rate(23.1%, P = 0.01), and type Ⅱ and Ⅳ patients had the highest cannulation success rates(99.4% in type Ⅱ and 99.3% in type Ⅳ, P < 0.001). In a multivariableadjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio(OR) = 1.87, 95% confidence interval(CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group,the difficulty of cannulation in the type Ⅰ PAD group according to the Li-Tanaka classification was greater(OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower(OR = 0.27, 95%CI: 0.11-0.66, P < 0.001),while it was higher in the type Ⅱ PAD group(OR = 4.44, 95%CI: 1.61-12.29, P <0.01).CONCLUSION Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

Three initial diets for management of mild acute pancreatitis:A meta-analysis

AIM:To compare non-liquid and clear-liquid diets,and to assess whether the latter is the optimal treatment for mild acute pancreatitis.METHODS:The Cochrane Library,PUBMED,EMBASE,EBM review databases,Science Citation Index Expanded,and several Chinese databases were searched up to March 2011.Randomized controlled trials(RCTs) that compared non-liquid with clear-liquid diets in patients with mild acute pancreatitis were included.A meta-analysis was performed using available evidence from RCTs.RESULTS:Three RCTs of adequate quality involving a total of 362 participants were included in the final analysis.Compared to liquid diet,non-liquid diet significantly decreased the length of hospitalization [mean difference(MD):1.18,95% CI:0.82-1.55;P﹤0.00001] and total length of hospitalization(MD:1.31,95% CI:0.45-2.17;P = 0.003).The subgroup analysis showed solid diet was more favorable than clear liquid diet in the length of hospitalization,with a pooled MD being-1.05(95% CI:-1.43 to-0.66;P﹤0.00001).However,compared with clear liquid diet,both soft and solid diets did not show any significant differences for recurrence of pain after re-feeding,either alone [relative risk(RR):0.95;95% CI:0.51-1.87;P = 0.88] and(RR:1.22;95% CI:0.69-2.16;P = 0.49),respectively,or analyzed together as non-liquid diet(RR:0.80;95% CI:0.47-1.36;P = 0.41).CONCLUSION:The non-liquid soft or solid diet did not increase pain recurrence after re-feeding,compared with the clear-liquid diet.The non-liquid diet reduced hospitalization.

Ectopic opening of the common bile duct into the duodenal bulb with recurrent choledocholithiasis: A case report

BACKGROUND Ectopic opening of the common bile duct is a condition with low incidence.Patients with an ectopic common bile duct opening have a high incidence of common bile duct stones and acute cholangitis.Patients with atypical symptoms and imaging findings are easily misdiagnosed;moreover,it is difficult to retrieve stones by endoscopic retrograde cholangiopancreatography,and common bile duct stones are prone to postsurgical recurrence.CASE SUMMARY A 45-year-old male patient presented with“intermittent upper abdominal pain and elevated liver enzymes for 1 wk”.Transabdominal ultrasound indicated dilation of the common bile duct and the presence of stones.Magnetic resonance imaging showed that the common bile duct was dilated with stones and that its opening was ectopic.Endoscopic retrograde cholangiopancreatography revealed an abnormal opening of the common bile duct into the duodenal bulb and the presence of common bile duct stones.Laparoscopic extrahepatic choledochectomy and hepatoenteric anastomosis were performed.After surgery,the patient recovered well and was discharged.The patient has been followed up for 2 years since the operation.He has not experienced stone recurrence,and his liver function and quality of life are good.CONCLUSION Improved understanding of ectopic opening of the common bile duct is needed for clinicians to provide patients with appropriate treatment.

Emergent Endoscopic Retrograde Cholangiopancreatography with Placement of Biliary Double Stents to Salvage Endoscopic Retrograde Cholangiopancreatography-lnduced Stapfer＇s Type Ⅱ Perforation

To the Editor：Endoscopic retrograde cholangiopancreatography （ERCP） plays a vital role in the management ofpancreaticobiliary diseases in recent years and it concomitantly carries a risk of complications including post-ERCP pancreatitis,cholangitis,bleeding,and perforation.The incidence of primary post-ERCP complications ranges from 5.4% to 23.0%,and ERCP-induced perforation can occur in 0.3-1.0% of cases,but the associated mortality is high ranging from 8% to 23%.[1] Because of the confluence of the bile duct and pancreatic duct meet at the papilla in proximity to the site of perforation in the duodenum,there is a potential risk of leakage of bile and pancreatic juice into the retroperitoneal space or peritoneum.Patients with Stapfer＇s Type Ⅱ perforation （perivaterian perforation） generally suffered from systemic inflammatory response syndrome,which could progress rapidly to acute lung injury and acute renal insufficiency and even multiple organ failure.All of these contribute to the significantly high mortality.A timely recognition and appropriate treatment are crucial to the management of ERCP-induced perforation to reduce the overall mortality.Conventionally,surgery remains the primary treatment for iatrogenic perforations.With the improvement in endoscopic technique and development of new accessories,nonsurgical management with endoscopic treatment of perforation is increasingly being reported.[2] We report a retrospective analysis of ERCP-induced Stapfer＇s Type Ⅱ perforations over a 5-year period managed with nonsurgical approach combined with salvage ERCP.