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.

T-tube drainage versus choledochojejunostomy in hepatolithiasis patients with sphincter of Oddi laxity: study protocol for a randomized controlled trial.

BACKGROUND: Residual and recurrent stones remain one of the most important challenges of hepatolithiasis and are reported in 20 to 50% of patients treated for this condition. To date, the two most common surgical procedures performed for hepatolithiasis are choledochojejunostomy and T-tube drainage for biliary drainage. The goal of the present study was to evaluate the therapeutic safety and perioperative and long-term outcomes of choledochojejunostomy versus T-tube drainage for hepatolithiasis patients with sphincter of Oddi laxity (SOL). METHODS/DESIGN: In total, 210 patients who met the following eligibility criteria were included and were randomized to the choledochojejunostomy arm or T-tube drainage arm in a 1:1 ratio: (1) diagnosed with hepatolithiasis with SOL during surgery; (2) underwent foci removal, stone extraction and stricture correction during the operation; (3) provided written informed consent; (4) was willing to complete a 3-year follow-up; and (5) aged between 18 and 70 years. The primary efficacy endpoint of the trial will be the incidence of biliary complications (stone recurrence, biliary stricture, cholangitis) during the 3 years after surgery. The secondary outcomes will be the surgical, perioperative and long-term follow-up outcomes. DISCUSSION: This is a prospective, single-centre and randomized controlled two-group parallel trial designed to demonstrate which drainage method (Roux-en-Y hepaticojejunostomy or T-tube drainage) can better reduce biliary complications (stone recurrence, biliary stricture, cholangitis) in hepatolithiasis patients with SOL. TRIAL REGISTRATION: Clinical Trials.gov: NCT04218669 . Registered on 6 January 2020.

Investigation the relaxant effects of proton pump inhibitors and their relaxation mechanism on sheep sphincter of Oddi.

BACKGROUND: Using a relaxant agent before an endoscopic retrograde cholangiopancreatography (ERCP) might reduce complications. STUDY AIMS: We aimed to investigate the relaxant effects of proton pump inhibitors (PPIs) on sheep sphincter of Oddi (SO) and the mechanisms that might take part in this relaxant effect. PATIENTS AND METHODS: The sheep SO was mounted in an organ bath filled with Krebs-Ringer bicarbonate solution under 1.5 g tension and the relaxant effects of PPIs were evaluated in the tissues precontracted by carbachol (10-6 mol/l). The relaxant responses to the PPIs were tested in the presence of various blockers to enlighten the underlying mechanism by the PPIs. RESULTS: The PPIs exerted relaxant responses in a concentration-dependent manner in the sheep SO (P < 0.05). Esomeprazole produced the strongest relaxation. The administration of atropine, indomethacin, L-NAME, methylene blue, clotrimazole, glibenclamide, and 4-aminopyridine into the organ baths did not change the relaxations induced by PPIs in vitro (P> 0.05). On the other hand, Ca+2-activated potassium channel blocker tetraethylammonium (TEA) reduced the relaxation responses created by PPIs (P < 0.05). CONCLUSIONS: The present study suggests that PPIs create relaxation on SO partially via Ca+2-activated potassium channels. PPIs, especially esomeprazole, may be beneficial during the ERCP procedure. Further clinical studies are needed to confirm our results.

Sphincter of Oddi dysfunction: sphincter of Oddi dysfunction or discordance? What is the state of the art in 2018?

PURPOSE OF REVIEW: To review important manuscripts published over the previous 2 years relative to sphincter of Oddi dysfunction (SOD). RECENT FINDINGS: The long-term outcomes of the Evaluating Predictors and Interventions of SOD (EPISOD) trial further substantiated results from the initial EPISOD study, reinforcing that neither endoscopic retrograde cholangiopancreatography-manometry nor endoscopic sphincterotomy are appropriate for SOD type III. Pain management in the latter patients has reverted to neuromodulating agents, and recent studies have suggested a role for duloxetine and potentially acupuncture. The functional role of the sphincter of Oddi has been reiterated with a report demonstrating a higher clinically significant pancreatic fistula rate in distal pancreatectomy patients treated with higher doses of postoperative narcotics. Moreover, the injection of periampullary botulinum toxin preoperatively has been shown to decrease these fistulas in a pilot trial. Additional studies have reinforced that eluxadoline can cause sphincter of Oddi spasm and pancreatitis. In contrast to approaching patients with acute relapsing pancreatitis using endoscopic retrograde cholangiopancreatography and manometry, previous and current studies suggest that endoscopic ultrasound should be done first and the role of SOD in idiopathic acute relapsing pancreatitis remains controversial. Finally, there remain widespread disparities in practice patterns in the approach to patients currently classified as SOD type II. SUMMARY: In contrast to historical manuscripts which stress the classical definitions of three types of SOD and their consequences, more recent manuscripts on this topic have focused on improving surgical outcomes based on the physiologic role of sphincter of Oddi, as well as the pharmacologic causes and treatments of SOD. The simplistic view that SOD, however it has been diagnosed, requires biliary or dual sphincterotomy is just that, simplistic and potentially misguided.

Adverse Events and Reinterventions Following Pancreatic Endoscopic Sphincterotomy.

OBJECTIVES: Pancreatic endoscopic sphincterotomy (PES) is an independent risk factor for short- and long-term adverse events (AEs) of endoscopic retrograde cholangiopancreatography. We sought to measure PES-specific AEs and trends in the use of PES. METHODS: This was a retrospective cohort of consecutive patients who underwent first-time PES between June 2008 and June 2015. Indications for PES were dichotomized: (1) structural pathology (chronic pancreatitis and local complications of acute pancreatitis) and (2) suspected sphincter pathology (idiopathic recurrent acute pancreatitis and sphincter of Oddi dysfunction). Rates of AEs and pancreatic orifice reinterventions were measured, with reintervention rates limited to those having a minimum of 12-month follow-up. RESULTS: Of 567 patients, 198 (34.9%) underwent PES for structural and 369 (65.1%) for suspected sphincter pathology. Rates of post-endoscopic retrograde cholangiopancreatography pancreatitis and unplanned hospitalization were high when PES was originally performed for suspected sphincter pathology (12.6% and 14.6%, respectively). The overall reintervention rate was 28.9% and significantly greater for sphincter (41.7%) compared with structural pathology (13.5%, P = 0.005). CONCLUSIONS: The likelihood of reintervention after PES is high, particularly when the primary indication is suspected sphincter pathology such as idiopathic recurrent acute pancreatitis. Further prospective studies are needed to clarify if and when this maneuver confers significant benefit to patients.

Does preserved sphincter of Oddi function prevent common bile duct stones recurrence in patients after endoscopic papillary balloon dilation?

BACKGROUND: Whether preserving sphincter of Oddi (SO) function by endoscopic papillary balloon dilation (EPBD) is beneficial for preventing recurrent common bile duct stone disease (CBDS) is controversial. The aim of this study was to measure sphincter of Oddi (SO) function by using SO manometry, and to evaluate the association with recurrent CBDS. METHODS: Patients with suspected CBDS who underwent successful EPBD were included. These patients underwent SO manometry at two months after EPBD with bile duct clearance. They were regularly followed for recurrent CBDS. RESULTS: From January 2000 to December 2009, 185 patients received EPBD and SO manometry was included. There were 64% male with mean age of 65 ± 15.6 years. Mean ballooning inflation size was 1.1 ± 0.19 cm and mean ballooning time was 4.5 ± 0.85 min 55.7% had a sphincter of Oddi basal pressure (SOBP) of 0 mmHg, 16.2% < 10 mmHg, 26.5% 10-40 mmHg, and 1.6% > 40 mmHg. In multivariate analysis, EPBD with balloon ≥1.2 cm was the only factor for loss of SO function. Moreover, patients with preserved SO function had higher stone recurrence rate (15% vs. 5%, p = 0.034). CONCLUSION: EPBD using balloon ≥1.2 cm is a major factor for loss of SO function, which seems to reduce the risk of recurrent CBD stones.

Bi-directional regulation of acupuncture on extrahepatic biliary system: An approach in guinea pigs.

Clinically, acupuncture affects the motility of the extrahepatic biliary tract, but the underlining mechanisms are still unknown. We applied manual acupuncture (MA) and electrical acupuncture (EA) separately at acupoints Tianshu (ST25), Qimen (LR14), Yanglingquan (GB34), and Yidan (CO11) in forty guinea pigs (4 groups) with or without atropinization under anesthesia while Sphincter of Oddi (SO) myoelectric activities and gallbladder pressure were monitored. In both MA and EA groups, stimulation at ST25 or LR14 significantly increased the frequency and amplitude of SO myoelectrical activities and simultaneously decreased the gallbladder pressure as compared to the pre-MA and pre-EA (P < 0.05). On the contrary, stimulation at GB34 or CO11 significantly decreased SO myoelectricity and increased the gallbladder pressure (P < 0.05). Pretreatment with atropine could abolish the effect of stimulation at acupoints ST25, GB34 and LR14 (P > 0.05), although significant myoelectricity increases were still inducible with MA or EA stimulation at CO11 (P < 0.05). In summary, acupuncture has bi-directional effects to gallbladder pressure and SO function, which probably due to autonomic reflex and somatovisceral interactions.

Impact of endoscopic papillary large-balloon dilation on sphincter of Oddi function: a prospective randomized study.

BACKGROUND AND AIMS: Endoscopic papillary balloon dilation (≤8 mm in diameter) preserves sphincter of Oddi (SO) function. However, it is still unknown whether papillary function is preserved after endoscopic papillary large-balloon dilation (EPLBD, ≥12 mm in diameter). We investigated SO function after EPLBD with or without endoscopic sphincterotomy (EST) by endoscopic manometry, up to 1 year after the procedure. METHODS: This was a prospective randomized study involving patients with bile duct stones ≥12 mm. Eighty-six patients who met the inclusion criteria were assigned randomly to either EPLBD alone or EST with EPLBD, and endoscopic manometric studies were performed. The primary outcome was comparison of the manometric data between the 2 groups and within each group both 1 week and 1 year after the procedure. RESULTS: One week after EPLBD alone and EST with EPLBD, the basal pressure of SO dropped from 30.4 (8.2) to 6.4 (8.4) mm Hg (P < .001) and 29.5 (18.9) to 2.9 (3.6) mm Hg (P < .001), respectively. SO function was not recovered at 1 year; the manometric measurements were similar to those taken at the 1-week time point in both groups. Similar outcomes were obtained in patients with EPLBD alone compared with those with EST and EPLBD, including the initial stone clearance rate (95.2% vs 97.7%, P = .612), the frequency of mechanical lithotripsy (21.4% vs 13.6%), and overall adverse events (11.9% vs 13.6%, P = 1.0) including the rate of pancreatitis after the procedure (7.1% vs 11.4%, P = .714). During an overall median follow-up of 17.8 months, the recurrence rate of bile duct stones was 16.7% in patients who underwent EPLBD alone and 15.9% in patients who underwent EST with EPLBD (P = .924). CONCLUSIONS: Both EPLBD alone and EST + EPLBD resulted in persistent and comparable loss of SO function after 1 year. EPLBD alone has similar efficacy and safety to those of EST with EPLBD with respect to removal of large stones.

Post-cholecystectomy syndrome and sphincter of Oddi dysfunction: past, present and future.

INTRODUCTION: Post-cholecystectomy syndrome and the concept of a causal relationship to sphincter of Oddi dysfunction, despite the controversy, has presented a clinically relevant conflict for decades. Historically surgeons, and now gastroenterologists have expended tremendous efforts towards trying to better understand the dilemma that is confounded by unique patient phenotypes. Areas covered: This review encompasses the literature from a century of experience on the topic of post-cholecystectomy syndrome. Relevant historical and anecdotal experiences are examined in the setting of insights from evaluation of recently available controlled data. Expert commentary: Historical observations and recent data suggest that patients with post-cholecystectomy syndrome can be categorized as follows. Patients with sphincter of Oddi stenosis will most often benefit from treatment with sphincterotomy. Patients with classic biliary pain and some objective evidence of biliary obstruction may have a sphincter of Oddi disorder and should be considered for endoscopic evaluation and therapy. Patients with atypical post-cholecystectomy pain, without any evidence consistent with biliary obstruction, and/or with evidence for another diagnosis or dysfunction should not undergo ERCP.

Effects of remifentanil on the sphincter of Oddi in a 3-year-old child: a case report.

Opioids cause spasm of the sphincter of Oddi. Remifentanil is metabolized enzymatically throughout the body. Its context-sensitive half-time is 3 to 4minutes. The effect of remifentanil on the sphincter of Oddi is unknown, especially in children. We recently encountered a patient in whom the administration of remifentanil caused spasm of the sphincter of Oddi, which resolved rapidly after discontinuation of remifentanil. A 3-year-old girl weighing 11.3kg was scheduled to undergo common bile duct excision with ductoplasty. Her diagnosis was congenital biliary dilatation. In the operating room, after achieving the initial induction through sevoflurane (5%) and intravenous rocuronium (10mg), she was intubated and administered a continuous paravertebral block by levobupivacaine (25mg/10mL +2.5mg/h). General anesthesia was maintained with sevoflurane (2%), remifentanil (0.5 µg kg(-1) min(-1)), and oxygen (fractional inspired oxygen tension, 0.33). The first intraoperative cholangiogram obtained via the cystic duct tube showed obstruction at the terminal end of the common bile duct. We injected scopolamine butylbromide (5mg, intravenous) to relax the sphincter of Oddi. However, the next cholangiogram obtained 3minutes later still showed an obstruction. We speculated that the obstruction may have been caused by remifentanil-induced spasm of the sphincter of Oddi. Therefore, we stopped administering remifentanil; 2minutes later, we achieved satisfactory passage of the contrast material to the duodenum. The predicted plasma concentrations of remifentanil at the time of stopping its administration and at the time of disobliteration were 6.38and 2.55ng/mL, respectively. The patient's postoperative course was uneventful. In patients who have spasms of the sphincter of Oddi during the administration of remifentanil, the resultant obstruction can be treated effectively by reducing the infusion rate of remifentanil.

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.

A Randomized, Clinical Trial Involving Different Surgical Methods Affecting the Sphincter of Oddi in Patients With Choledocholithiasis.

AIM: The purpose of the current study was to compare pressure changes in the sphincter of Oddi (SO) and stone recurrence after surgery in patients with choledocholithiasis who underwent laparoscopic common bile duct exploration during laparoscopic cholecystectomy (LC) or endoscopic sphincterotomy (EST) with LC, which may provide clinical evidence for choledocholithiasis patients to choose the appropriate surgical approach. MATERIALS AND METHODS: Fifty-one patients with choledocholithiasis were randomized to the EST/LC (group A 26 cases) or laparoscopic common bile duct exploration during LC group (group B 25 cases). We performed SO manometry during surgery and 3 months postoperatively on all patients. In addition, the duodenobiliary reflux test was performed during the third month postoperatively. All patients were followed for 24 to 30 months. RESULTS: In group A, the SO basal and contraction pressures were 30.88±16.11 and 77.46±23.62 mm Hg intraoperatively and 10.34±10.27 and 45.65±24.77 mm Hg 3 months postoperatively, respectively. In group B, the SO basal and contraction pressures were 27.80±15.88 and 73.96±23.99 mm Hg intraoperatively and 15.43±7.36 and 59.56±22.61 mm Hg 3 months postoperatively, respectively. During the third month postoperatively, duodenobiliary reflux was demonstrated in 16 of 26 and 7 of 25 patients in groups A and B, respectively (P<0.05). During follow-up, the stone recurrence rates were 6 of 26 in group A and 1 of 25 in group B (P<0.05). CONCLUSIONS: After EST, the SO basal and contraction pressures decreased, and the duodenobiliary reflux and stone recurrence rates increased. Thus, EST should be selected with care.

Roles of Sphincter of Oddi Laxity in Bile Duct Microenvironment in Patients with Cholangiolithiasis: From the Perspective of the Microbiome and Metabolome.

BACKGROUND: Bile duct microenvironment plays several key roles in cholangiolithiasis occurrence. Sphincter of Oddi laxity (SOL) is associated with cholangiolithiasis, probably due to enhanced reflux of intestinal contents that changes the microenvironment. However, the microenvironment has not been investigated comprehensively. STUDY DESIGN: Patients with cholangiolithiasis were consecutively recruited and their bile was collected intraoperatively for high-throughput experiments. Pyrosequencing of 16S ribosomal RNA gene was performed to characterize the microbiota in the bile. A liquid chromatography mass spectrometry-based method was used to profile bile composition. Clinical manifestation, microbiome, and bile composition were compared between patients with and without SOL. RESULTS: Eighteen patients with SOL and 27 patients without SOL were finally included. Patients with SOL showed more severe inflammation. Bacteria in the bile duct were overwhelmingly aerobes and facultative anaerobes. Proteobacteria and Firmicutes were the most widespread phylotypes, especially Enterobacteriaceae. Compared with those without SOL, patients with SOL possessed more varied microbiota. In the SOL group, pathobionts, such as Bilophila and Shewanella algae had richer communities, and harmless bacteria were reduced. Metabolomics analysis showed the differences in bile composition between groups were mainly distributed in lipids and bile acids. Particularly, the increased abundance of Bilophila involved in taurine metabolism was associated with reduced contents of taurine derivatives in the bile of patients with SOL. CONCLUSIONS: A bile duct microenvironment with more severe bacterial infection and stronger lithogenicity was found in patients with SOL. The findings suggest a possible mechanism of cholangiolithiasis and provide the basis for future strategies for prevention of cholangiolithiasis recurrence.

ENDOSCOPIC METHODS OF DIAGNOSTICS AND TREATMENT OF PAPILLOSTENOSIS.

Differential diagnostics of papillospasm and papillostenosis should be based on the complex of clinical and instrumental researches with the priority to endoscopic technologies. Conservative therapy should be considered as optimal option of treatment for the patients with papillospasm. Preference of endoscopic operations have to be in case of revealed papillostenosis of different degree. Similar differentiated diagnostics and treatment management justified in 90% of cases and led to improvement of patient's conditions and their recovery.

Oddi sphincter preserved cholangioplasty with hepatico-subcutaneous stoma for hepatolithiasis.

AIM: To evaluate the long-term outcomes of Oddi sphincter preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS) and risk factors for recurrence in hepatolithiasis. METHODS: From March 1993 to December 2012, 202 consecutive patients with hepatolithiasis underwent OSPCHS at our department. The Oddi sphincter preserved procedure consisted of common hepatic duct exploration, stone extraction, hilar bile duct plasty, establishment of subcutaneous stoma to the bile duct. Patients with recurrent stones can undergo stone extraction and/or biliary drainage via the subcutaneous stoma which can be incised under local anesthesia. The long-term results were reviewed. Cox regression model was employed to analyze the risk factors for stone recurrence. RESULTS: Ninety-seven (48.0%) OSPCHS patients underwent hepatic resection concomitantly. The rate of surgical complications was 10.4%. There was no perioperative death. The immediate stone clearance rate was 72.8%. Postoperative cholangioscopic lithotomy raised the clearance rate to 97.0%. With a median follow-up period of 78.5 mo (range: 2-233 mo), 24.8% of patients had recurrent stones, 2.5% had late development of cholangiocarcinoma, and the mortality rate was 5.4%. Removal of recurrent stones and/or drainage of inflammatory bile via subcutaneous stoma were conducted in 44 (21.8%) patients. The clearance rate of recurrent stones was 84.0% after subsequent choledochoscopic lithotripsy via subcutaneous stoma. Cox regression analysis showed that residual stone was an independent prognostic factor for stone recurrence. CONCLUSION: In selected patients with hepatolithiasis, OSPCHS achieves excellent long-term outcomes, and residual stone is an independent prognostic factor for stone recurrence.