Endoscopic endoclip papilloplasty preserves sphincter of oddi function.

BACKGROUND: Endoscopic sphincterotomy (EST) can destroy sphincter of Oddi (SO) structure and function. The purpose of this study was to assess the feasibility of endoscopic endoclip papilloplasty (EEPP) in restoring SO function after EST. METHODS: Seven 26-week-old domestic pigs were divided into control and EEPP groups. Necropsy and haematoxylin-eosin staining plus anti-α-smooth muscle actin (α-SMA) staining of papilla and sphincter of Oddi manometry (SOM) were conducted in animals at three independent time points. RESULTS: EST and EEPP were safely performed in all 7 pigs without serious adverse events. For primary outcome, compared to the controls, EEPP generated smaller dilation and less inflammation. Fibrous repair of the papilla was observed at 24 weeks after EEPP. For secondary outcome, in the control group, SO basal pressure (17.25 ± 18.14 to 5.50 ± 0.71 mmHg), SO contraction amplitude (46.00 ± 19.20 to 34.50 ± 48.79 mmHg), peak (4.50 ± 4.04 to 1.50 ± 2.12) and frequency (3.05 ± 3.29 to 1.41 ± 2.19/min) were reduced after EST. Further reductions to almost 0 of these SOM parameters were observed 3 weeks later, including common bile duct pressure and SO contraction period. In contrast, in the EEPP group, these manometric data were recovered to pre-EST levels, including CBD pressure (11.5 ± 7.31 vs 11 ± 2.16 mmHg), SO pressure (17.50 ± 17.75 vs 18.20 ± 21.39 mmHg) and SO contraction amplitude (53.67 ± 21.54 vs 60.00 ± 36.08 mmHg). However, no significant differences were observed between control and EEPP groups by Student t test. CONCLUSIONS: In this porcine study, EEPP accelerated and improved papillary healing after EST, further preserved SO function.

Effects of sphincter of Oddi motility on the formation of cholesterol gallstones.

AIM: To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs. METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation. RESULTS: The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups. CONCLUSION: A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.

Vascular endothelial growth factor levels in bile distinguishes pancreatic cancer from other etiologies of biliary stricture: a pilot study.

BACKGROUND: Determining the benign or malignant nature of biliary strictures can be challenging. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. OBJECTIVE: The purpose of this study was to investigate whether VEGF levels in bile aspirated during endoscopic retrograde cholangiography (ERCP) can distinguish pancreatic cancer from other causes of biliary stricture. METHODS: Bile was directly aspirated in 53 consecutive patients from March 2012 to October 2012 during ERCP from the common bile duct including 15 with pancreatic cancer, 18 with primary sclerosing cholangitis (PSC), nine with cholangiocarcinoma (CCA), and 11 with benign biliary conditions (sphincter of Oddi and choledocholihiasis). Levels of VEGF in bile were measured. The diagnostic performance was then validated in a second, independent validation cohort of 18 patients (pancreatic cancer n = 10, benign n = 8). RESULTS: A total of 53 consecutive patients were recruited. The median bile VEGF levels were significantly elevated in patients with pancreatic cancer (1.9 ng/ml (interquartile range [IQR] 0.7, 2.2) compared to those with benign biliary conditions (0.3 ng/ml [IQR 0.2, 0.6]; p < 0.001), PSC (0.7 ng/ml [IQR 0.5, 0.9]; p = 0.02) or CCA (0.4 ng/ml [IQR 0.1, 0.5]; p < 0.001). A VEGF cut-off value of 0.5 ng/ml distinguished pancreatic cancer from CCA with a sensitivity and specificity of 93.3 and 88.9 %, respectively, and area under curve (AUC) of 0.93, and from benign conditions with a sensitivity and specificity of 93.3 and 72.7 %, respectively, with AUC of 0.89. The diagnostic accuracy of biliary VEGF was confirmed in the second independent validation cohort. CONCLUSIONS: This study suggests that measurement of biliary VEGF-1 levels distinguishes patients with pancreatic cancer from other etiologies of biliary stricture. This may be particularly relevant in approaching patients with indeterminate biliary stricture.

Differences in phosphatidylcholine and bile acids in bile from Egyptian and UK patients with and without cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients. OBJECTIVES: This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease. METHODS: A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt (n = 4) or the UK (n = 4) and 21 patients with benign biliary disease (choledocholithiasis [n = 8], sphincter of Oddi dysfunction [n = 8], primary sclerosing cholangitis [n = 5]). RESULTS: Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases (P = 0.013 and P < 0.01, respectively). CONCLUSIONS: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.

Biliary microlithiasis, sludge, crystals, microcrystallization, and usefulness of assessment of nucleation time.

BACKGROUND: The process of microcrystallization, its sequel and the assessment of nucleation time is ignored. This systematic review aimed to highlight the importance of biliary microlithiasis, sludge, and crystals, and their association with gallstones, unexplained biliary pain, idiopathic pancreatitis, and sphincter of Oddi dysfunction. DATA SOURCES: Three reviewers performed a literature search of the PubMed database. Key words used were "biliary microlithiasis", "biliary sludge", "bile crystals", "cholesterol crystallisation", "bile microscopy", "microcrystal formation of bile", "cholesterol monohydrate crystals", "nucleation time of cholesterol", "gallstone formation", "sphincter of Oddi dysfunction" and "idiopathic pancreatitis". Additional articles were sourced from references within the studies from the PubMed search. RESULTS: We found that biliary microcrystals account for almost all patients with gallstone disease, 7% to 79% with idiopathic pancreatitis, 83% with unexplained biliary pain, and 25% to 60% with altered biliary and pancreatic sphincter function. Overall, the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55% to 87% and a specificity of 100%. In idiopathic pancreatitis, the presence of microcrystals ranges from 47% to 90%. A nucleation time less than 10 days in hepatic bile or ultra-filtered gallbladder bile has a specificity of 100% for cholesterol gallstone disease. CONCLUSIONS: Biliary crystals are associated with gallstone disease, idiopathic pancreatitis, sphincter of Oddi dysfunction, unexplained biliary pain, and post-cholecystectomy biliary pain. Pathways of cholesterol super-saturation, crystallisation, and gallstone formation have been described with scientific support. Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation.

Sphincter of Oddi hypomotility and its relationship with duodenal-biliary reflux, plasma motilin and serum gastrin.

AIM: To detect whether patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux by measuring the radioactivity of Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the bile and whether the patients with duodenal-biliary reflux have sphincter of Oddi hypomotility, by measuring the level of plasma and serum gastrin of the patients. Finally to if there is close relationship among sphincter of Oddi hypomotility, duodenal-biliary reflux and gastrointestinal peptides. METHODS: Forty-five patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group. The level of plasma and serum gastrin of the patients and of 12 healthy volunteers were measured by radioimmunoassay. Thirty-four were selected randomly to undergo choledochoscope manometry. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duration of contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: Sixteen (35.6%) patients were detected to have duodenal-biliary reflux. SOBP, SOCA and CBDP in the reflux group were much lower than the control group (t=5.254, 3.438 and 3.527, P<0.001). SOD of the reflux group was shorter than the control group (t=2.049, P<0.05). The level of serum gastrin and plasma motilin of the reflux group was much lower than the control group (t= -2.230 and -2.235, P<0.05). There was positive correlation between the level of plasma motilin and SOBP and between the level of serum gastrin and SOBP and CBDP. CONCLUSION: About 35.9% of the patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of them have sphincter of Oddi hypomotility and the decreased level of plasma motilin and serum gastrin. The disorder of gastrointestinal hormone secretion may result in sphincter of Oddi dysfunction. There is a close relationship between sphincter of Oddi hypomotility and duodenal-biliary reflux.

Bile-reflux into the pancreatic ducts is associated with the development of intraductal papillary carcinoma in hamsters.

BACKGROUND: Reflux of pancreatic juice into the biliary tract is a well-known risk factor for the development of biliary carcinoma. In this study, we investigated the significance of bile-reflux into the pancreatic ducts in pancreatic carcinogenesis, especially in the development of carcinoma in the main pancreatic duct in hamsters. MATERIALS AND METHODS: Syrian hamsters were subjected to three different surgical procedures: cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (Model A); cholecystoduodenostomy along with a dissection of the common bile duct (Model B); or simple laparotomy (Model C). The animals then received weekly subcutaneous injections of N-nitrosobis(2-oxopropyl)amine (BOP), for 9 weeks, and were killed for pathological investigation at 16 weeks after the initial BOP administration. RESULTS: Pancreas carcinomas developed in 95, 88, and 90% of the Model A hamsters (n = 22), B (n = 24), and C (n = 21), respectively. The induced pancreatic tumors were histologically classified into four types: papillary; tubular; cystic adenocarcinoma; or intraductal carcinoma of the main pancreatic duct consisting of intraductal papillary carcinoma (IPC) and intraductal tubular carcinoma (ITC). The number and the incidence of IPCs induced in Model A hamsters were 24 lesions and 77% and were statistically higher than those in Model B (7 lesions and 29%) and C hamsters (7 lesions and 33%) (P < 0.01). Bile-reflux into the pancreatic ducts was clearly demonstrated in only hamsters of Model A by means of Indocyanine green injection via the portal vein. Proliferative cell nuclear antigen labeling indices of the epithelial cells in the main pancreatic duct in hamsters, with no BOP treatment, were 3.8, 0.8, and 1.1% in Models A (n = 10), B (n = 10), and C (n = 10), respectively, and the difference was statistically significant (P < 0.01). CONCLUSIONS: Our findings suggest that bile-reflux into the pancreatic ducts is a significant factor predisposing to the development of IPC of the pancreas through an acceleration of epithelial cell kinetics of the main pancreatic duct.