Unaccounted Gallbladder.

Gallbladder agenesis is a rare anatomical variant, and most cases are asymptomatic and diagnosed on autopsy. Few of them may present with features suggestive of biliary tract pathology. A 32-year-old male presented with complaints of intermittent epigastric pain for three months. Abdominal ultrasonography was suggestive of chronic calculous cholecystitis, and he was planned for laparoscopic cholecystectomy. However, no gallbladder was found during the surgery. Postoperative evaluation was suggestive of an absent gallbladder with a normal ductal system. A provisional diagnosis of sphincter of Oddi dysfunction was made based on his symptoms. Congenital absence of gallbladder is a rare anomaly and only a few of the affected individuals are symptomatic. Lack of specific features, coupled with the inability of standard abdominal ultrasonography to detect the absence of gallbladder, can put the treating surgeon in a dilemma intraoperatively. Agenesis of the gallbladder is often missed and this entity should be kept in mind while having difficulty in visualizing the gallbladder. An astute surgeon should be wary of this diagnosis during difficult dissection to avoid bile duct injuries.

Current treatment of biliary Sphincter of Oddi Dysfunction.

The sphincter of Oddi is a delicate neuromuscular structure located at the junction of the biliary-pancreatic system and the duodenum. Sphincter of Oddi Dysfunction (SOD) can result in various clinical manifestations, including biliary-type pain and recurrent idiopathic pancreatitis. The management of SOD has been challenging. With the publication of the landmark Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial and the Rome IV consensus, our clinical practice in the treatment of SOD has changed significantly in recent years. Currently, the management of type II SOD remains controversial and there is a lack of non-invasive therapy options, particularly for patients not responding to endoscopic treatment. In this mini review, we aimed to discuss the current knowledge on the treatment of biliary SOD.

Sphincter of oddi dysfunction induced by ketamine: A case report.

Key Clinical Message: Chronic ketamine use can lead to sphincter of oddi dysfunction (SOD), causing various hepatobiliary complications. Recognizing substance abuse history is vital for early detection. Timely intervention can prevent irreversible liver and pancreas damage. Abstract: Ketamine is commonly abused as a recreational drug worldwide due to its ability to induce euphoria-like effects. Ketamine abuse is associated with many hepatobiliary side effects ranging from cholestasis to biliary sepsis and death. Here we present a case of a young 29-year female with upper abdominal pain due to SOD resulting from chronic use of ketamine. SOD can result in obstruction or dysfunction of the bile and pancreatic ducts. Ketamine induces SOD by activation of the muscarinic receptors in the sphincter of oddi. Detail history of substance abuse is crucial for early identification of ketamine-induced SOD. Early identification and treatment of this rare condition can prevent permanent injury to the liver and pancreas.

Rise in First-Time ERCP for Benign Indications >1 Year After Cholecystectomy Is Associated With Worse Outcomes.

BACKGROUND & AIMS: Greater availability of less invasive biliary imaging to rule out choledocholithiasis should reduce the need for diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in patients who have a remote history of cholecystectomy. The primary aims were to determine the incidence, characteristics, and outcomes of individuals who undergo first-time ERCP >1 year after cholecystectomy (late-ERCP). METHODS: Data from a commercial insurance claim database (Optum Clinformatics) identified 583,712 adults who underwent cholecystectomy, 4274 of whom underwent late-ERCP, defined as first-time ERCP for nonmalignant indications >1 year after cholecystectomy. Outcomes were exposure and temporal trends in late-ERCP, biliary imaging utilization, and post-ERCP outcomes. Multivariable logistic regression was used to examine patient characteristics associated with undergoing late-ERCP. RESULTS: Despite a temporal increase in the use of noninvasive biliary imaging (35.9% in 2004 to 65.6% in 2021; P < .001), the rate of late-ERCP increased 8-fold (0.5-4.2/1000 person-years from 2005 to 2021; P < .001). Although only 44% of patients who underwent late-ERCP had gallstone removal, there were high rates of post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%). Factors associated with late-ERCP included concomitant disorder of gut-brain interaction (odds ratio [OR], 6.48; 95% confidence interval [CI], 5.88-6.91) and metabolic dysfunction steatotic liver disease (OR, 3.27; 95% CI, 2.79-3.55) along with use of anxiolytic (OR, 3.45; 95% CI, 3.19-3.58), antispasmodic (OR, 1.60; 95% CI, 1.53-1.72), and chronic opioids (OR, 6.24; 95% CI, 5.79-6.52). CONCLUSIONS: The rate of late-ERCP postcholecystectomy is increasing significantly, particularly in patients with comorbidities associated with disorder of gut-brain interaction and mimickers of choledocholithiasis. Late-ERCPs are associated with disproportionately higher rates of adverse events, including initiation of chronic opioid use.

Spasmolytic Effect of Flopropione Does Not Involve Catechol-O- methyltransferase (COMT) Inhibition.

Flopropione (Flo) has been used for gallstone and urolithiasis as a spasmolytic agent almost exclusively in Japan. According to the package insert, its main mechanism is catechol-O-methyltransferase (COMT) inhibition and anti-serotonergic effect. This is obviously contrary to pharmacological common sense, but it is described that way in pharmacology textbooks and occurs in questions in the National Examination for Pharmacists in Japan. As this is a serious problem in education, we re-examined the action of Flo. The guinea pig ureter was hardly contracted by serotonin, but noradrenaline (NA) elicited repetitive twitch contraction, which was inhibited by Flo. The sphincter of Oddi (SO) exhibited a spontaneous repetitive twitch contraction, which was inhibited by NA and Flo. The inhibitory effect of NA was reversed by α- and ß-blockers, whereas that of Flo was not. Entacapone, a representative COMT inhibitor, did not affect the movement of the ureter and the SO. Nifedipine suppressed carbachol-induced contraction of the taenia coli, spontaneous movement of the SO, and NA-induced contraction of the ureter to almost the same extent, whereas Flo did not inhibit the taenia coli, but inhibited the contraction of the SO and the ureter. The inhibitory pattern of Flo resembled that of the ryanodine receptor agonist 4-chloro-m-cresol and the inositol 1,4,5-trisphosphate (IP3) receptor antagonist 2-aminoethoxydiphenyl borate. It is concluded that COMT inhibition or serotonin inhibition is not involved in the spasmolytic action of Flo. Flo might act on ryanodine receptors and/or IP3 receptors, which are responsible for periodic Ca release from Ca stores, to disrupt coordinated Ca dynamics.

Sphincter of Oddi Dysfunction Induces Gallstone by Inhibiting the Expression of ABCB11 via PKC-α.

The abnormal increase of Oddi sphincter pressure and total bile duct pressure may play an important role in the formation of cholesterol stones, but the specific molecular mechanism is still unclear. This study aims to investigate it through in vitro and in vivo experiments. A mouse model of Oddi sphincter dysfunction was constructed by stone-inducing diet. We compared the two groups with PKC-α inhibitor GÖ6976 and PKC-α agonist thymeleatoxin. Oddi sphincter pressure and total bile duct pressure were measured. Biochemical analysis of total cholesterol, bile acid and bilirubin was then conducted. The histopathologic changes of bile duct were observed by HE staining and the ultrastructure of liver cells and surrounding tissues was observed by transmission electron microscopy. Through the above experiments, we found that the change of PKC-α expression may affect the formation process of gallstones. The relationship between PKC-α and ABCB11 was further verified by in vitro and in vivo experiments. Our results suggest that ABCB11 and PKC-α are co-expressed in the tubule membrane of hepatocytes and interact with each other in hepatocytes. The high cholesterol diet further enhances the activation of PKC-α and thus reduces the expression of ABCB11. The formation of cholesterol stones is associated with the down-regulation of ABCB11 expression in the tubule membrane of hepatocytes due to kinase signaling. This is the first study to demonstrate that sphincter of Oddi dysfunction induces gallstones through PKC-α inhibition of ABCB11 expression.

Contemporary Outcomes of Transduodenal Sphincteroplasty: the Importance of Surgical Quality.

BACKGROUND: Sphincter of Oddi dysfunction (SOD) is managed primarily by endoscopic sphincterotomy (ES); however, surgical transduodenal sphincteroplasty (TDS) is a treatment option for select patients. In our high-volume pancreatico-biliary practice, we have observed variable outcomes among TDS patients; therefore, we sought to determine preoperative predictors of durable improvement in quality of life. METHODS: SOD patients treated by TDS between January 2006 and December 2015 were studied. The primary outcome measure was long-term changes in quality of life after sphincteroplasty. The secondary outcome measure examined postoperative outcomes, including postoperative complications, need for repeat procedures, and readmission rates. Perioperative data were abstracted, and the SF-36 quality-of-life (QoL) survey was administered. Standard statistical analysis included non-parametric methods to examine bivariate associations. RESULTS: Eighty-eight patients had an average follow-up duration of 6.7 (± 2.9) years. Thirty (34%) patients were naïve to endoscopic therapy. Patients with prior endoscopy averaged 2.1 procedures (range 1 to 13) prior to surgery. Perioperative morbidity was 27%; one postoperative death was caused by severe acute pancreatitis. Twenty-nine (33%) patients required subsequent biliary-pancreatic procedures. QoL analysis from available patients showed that 66% were improved or much improved. With multivariable analysis including SOD type and prior endoscopic instrumentation, freedom from surgical complication was the only variable that correlated significantly with a good outcome (p < 0.02). CONCLUSION: Surgical transduodenal sphincteroplasty provides durable symptom management for select patients with sphincter of Oddi dysfunction. Minimizing surgical complications optimizes long-term outcomes.

Intrahepatic Gallbladder Rupture and Biloma Mimicking Pulmonary Embolism Following Orthopedic Surgery.

In this case report, a 75-year-old male with a history of coronary artery disease, type 2 diabetes, hypertension, and benign prostate hypertrophy developed postoperative fever and chest pain following left knee arthroplasty. Upon admission to the emergency department, pulmonary embolism was considered highly probable, and the patient was treated with anticoagulation and antibiotics due to diagnostic uncertainty. However, further investigations revealed a complex condition involving an intraparenchymal gallbladder rupture resulting in a biloma secondary to choledocholithiasis. The patient's history of receiving spinal anesthesia with intrathecal morphine was identified as a potential causative factor to the sphincter of Oddi constriction, leading to increased biliary pressure and gallbladder rupture. This case highlights the importance of having a broad differential diagnosis in postoperative patients, especially when the clinical presentation is atypical. With the diagnosis being confirmed, the patient underwent successful treatment, including biliary stenting, drainage of the biloma, and ultimately cholecystectomy. This case underlines the need for vigilance and a multidisciplinary approach in managing complex postoperative complications, emphasizing that clinical presentations may sometimes deviate significantly from the expected, requiring further investigation and individualized treatment.

The efficacy and safety of endoscopic sphincterotomy in patients with Sphincter of Oddi dysfunction: a systematic review and meta-analysis.

OBJECTIVE: Sphincter of Oddi dysfunction (SOD) has been used to describe patients with RUQ abdominal pain without an etiology. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of ES (endoscopic sphincterotomy) for SOD. METHODS: The study methodology follows the PRISMA guidelines. A comprehensive search was conducted using MEDLINE and EMBASE databases for RCTs with ES in patients with SOD. The primary outcome assessed was the improvement of abdominal pain after ES/sham. A random effects model was used to calculate pooled estimates for each outcome of interest. RESULTS: Of the initial 55 studies, 23 were screened and thoroughly reviewed. The final analysis included 3 studies. 340 patients (89.7% women) with SOD were included. All patients had a cholecystectomy. Most included patients had SOD type II and III. The pooled rate of technical success of ERCP was 100%. The average clinical success rate was 50%. The pooled cumulative rate of overall AEs related to all ERCP procedures was 14.6%. In the sensitivity analysis, only one study significantly affected the outcome or the heterogeneity. CONCLUSION: ES appears no better than placebo in patients with SOD type III. Sphincterotomy could be considered in patients with SOD type II and elevated SO basal pressure.

My 40-Year Encounter with ERCP: A Saga of Service, Syndromes, and Solutions.

Endoscopic retrograde cholangiopancreatography (ERCP) has been a significant development in gastrointestinal endoscopy. I did my first ERCP at SKIMS on December 5, 1982, and over the last 40 years, I have performed 10,100 ERCP procedures, including 600 Sphincter of Oddi manometries (SOM), and 3200 therapeutic ERCPs. We were confronted with many clinical challenges that needed answers by applying ERCP as a primary diagnostic tool. These studies gave birth to and/or recognition of several clinical syndromes. The hepatobiliary and pancreatic ascariasis (HBPA) as a clinical disease was recognized in 1985. The nematode, Ascaris lumbricoides, was the most common cause of hepatobiliary and pancreatic diseases in Kashmir, and its impact on healthcare, clinical profile, management policies, and control measures was identified. Kashmir was recognized as an endemic zone for recurrent pyogenic cholangitis (RPC), which constituted 12.5% of all biliary diseases. RPC in this population was found essentially to be an aftermath of HBPA. A subset of patients with hepatic hydatidosis with rupture into the biliary tract was recognized at ERCP and primarily treated by endotherapy. Cholangiographic abnormalities in children with portal cavernoma evolved into the recognition of portal biliopathy. Extensive studies of the sphincter of Oddi manometry in patients with unexplained biliary and/or pancreatic pain following cholecystectomy identified the entity of the sphincter of Oddi dyskinesia (SOD). In a cross-over trial, Nifedipine, compared with a placebo, showed a significant clinical response in 20 of 28 such patients. ERCP studies done in patients with tropical calcific pancreatitis showed an anomalous union of bile and pancreatic ducts. Forty of the 220 patients with liver transplantation had biliary complications namely biliary leaks, bile duct strictures, SOD, and recurrence of underlying primary biliary cholangitis. Biliary complications caused considerable morbidity and mortality in patients with liver transplantation.

Acute Recurrent Pancreatitis With Exclusion of Biliary Causes in a Young Female Patient.

Biliary pathologies are common causes of acute pancreatitis, including gallbladder cholesterolosis and gallstone pancreatitis. Nevertheless, after these two pathologies have been excluded, a broader differential and less common etiologies must be considered. Here we report an 18-year-old female with preliminary diagnosis of gallstone pancreatitis who underwent cholecystectomy and intraoperative cholangiogram resulting in uneventful recovery and resolution of symptoms. She returned three times within the month with symptoms of acute pancreatitis. We discussed alternative etiologies of her pancreatitis after exclusion of other causes with extensive imaging and laboratory evaluation.

Transduodenal Sphincteroplasty: A Visual Case Study.

BACKGROUND: Sphincter of Oddi dysfunction is a challenging and rare clinical entity resulting in pancreatobiliary pain and stasis of bile and pancreatic juice. This problem was classically treated with surgical therapy, but as classification of the disease has changed and newer methods of endoscopic evaluation and therapy have evolved, operative transduodenal sphincteroplasty is now generally reserved as a final therapeutic option for these patients. In this video and manuscript, we describe our approach to operative transduodenal sphincteroplasty in a patient with type I Sphincter of Oddi dysfunction. METHODS: A 50-year-old female with history of Roux-en-Y gastric bypass presented with episodic right-upper-quadrant and epigastric abdominal pain with associated documented elevations in liver chemistries. Preoperative cross-sectional imaging demonstrated dilation of her common bile duct. After multidisciplinary discussion, the decision was made to pursue operative transduodenal sphincteroplasty. RESULTS: All key operative steps of the transduodenal sphincteroplasty are demonstrated in the embedded video. Key operative steps include laparotomy, generous Kocher maneuver, and duodenotomy over the ampulla, allowing access for sequential biliary and pancreatic sphincterotomies and sphincteroplasties with absorbable suture. The duodenotomy and abdominal fascia are then closed. Our patient underwent sequential diet advancement and was discharged to home on postoperative day five. At clinic follow-up, pancreatobiliary-type pain had resolved. CONCLUSION: The embedded video demonstrates a case of operative transduodenal sphincteroplasty, which can provide durable results in appropriate patient populations.

Meta-analysis on clinical outcomes of suprapapillary versus transpapillary stent insertion in malignant biliary obstruction.

BACKGROUND/AIMS: Endoscopic biliary stenting is an essential treatment for malignant biliary obstruction (MBO). However, the optimal location for the placement of metal stents (MS) or plastic stents (PS) during the management of MBO, whether above (suprapapillary) or across (transpapillary) the sphincter of Oddi (SO), has not been thoroughly evaluated. This meta-analysis aims to compare the clinical outcomes associated with endoscopic retrograde cholangiopancreatography (ERCP)-guided biliary stents placed above and across the SO in patients with MBO. METHODS: A comprehensive search of electronic databases was carried out to identify studies published from inception to April 2022. The clinical outcomes examined including stent patency, stent occlusion, and overall adverse events (AEs) such as cholangitis, post-ERCP pancreatitis (PEP), cholecystitis, stent migration, and bleeding. The selection of a random-effects model or fixed-effects model was based on the presence of heterogeneity. RESULTS: A total of 12 articles involving 751 patients were analyzed. The findings showed that the suprapapillary approach had longer stent patency compared to the transpapillary approach (mean difference: 38.58; 95% confidence interval 16.02-61.14, P < 0.0001). Additionally, the suprapapillary approach was associated with a lower risk of stent occlusion and overall AEs (P = 0.04, P = 0.002, respectively), particularly in the incidence of PEP (P = 0.009). The incidence of cholangitis, cholecystitis, stent migration, and bleeding were similar between the suprapapillary and transpapillary approaches. The subgroup analyses indicated that suprapillary PS had a significant decrease in the incidence of stent occlusion and longer stent patency, while suprapillary MS had a significant decrease in the incidence of overall AEs and PEP than the transpapillary approach. CONCLUSION: Compared with the transpapillary approach, the suprapapillary stent had superiority in longer stent patency, lower rates of stent occlusion and overall AEs, and notably, a lower incidence of PEP. The incidence of cholangitis, cholecystitis, stent migration, and bleeding were similar between the suprapapillary and transpapillary approaches. Further large-scale randomized controlled studies are needed to confirm our findings. REGISTRATION NO: CRD42022336435.

Botulinum Toxin A Use in the Gastrointestinal Tract: A Reappraisal After Three Decades.

The discovery of botulinum toxin A (BTX)'s therapeutic properties has led to studies evaluating its usefulness in multiple medical disorders. Its use in the gastrointestinal (GI) tract has been studied for 30 years. Multiple databases, including PubMed, AccessMedicine, ClinicalKey, Cochrane Library, Embase, and Medline, were used to review research from case series to randomized controlled trials on BTX use in the GI tract. This article reviews the current literature on the efficacy of BTX and the strength of recommendations for or against its use in various disorders, including cricopharyngeal dysphagia, achalasia, nonachalasia motility disorders, gastroparesis, obesity, sphincter of Oddi disorders, chronic anal fissure, chronic idiopathic anal pain, and anismus. The appeal of BTX comes from its simplicity of administration, good safety profile, and reliability in decreasing muscular tone. However, there are several drawbacks that limit its use, including the lack of long-term efficacy and/or limited data in many GI disorders.

Sphincter of Oddi dysfunction that could not be diagnosed with Rome IV: a case report.

A 30-year-old female patient presented with monthly episodes of severe intermittent upper abdominal pain, especially after consuming fatty meals. Over a period of 5 years, she visited the emergency department 21 times due to the intensity of the pain. Although the pain appeared consistent with biliary pain, both blood and imaging tests showed no abnormalities. Despite not meeting the Rome IV criteria, we suspected sphincter of Oddi dysfunction (SOD). To further investigate, we conducted hepatobiliary scintigraphy (HBS), which revealed a clear delay in bile excretion. With the patient's informed consent, we performed endoscopic sphincterotomy (EST) and as of 10 months later, there have been no recurrences. This case demonstrates an instance of SOD that could not be diagnosed using the Rome IV criteria alone but was successfully identified through HBS. It underscores the possibility of hidden cases of SOD among patients who regularly experience severe epigastric pain, where routine blood or imaging tests may not provide a diagnosis. HBS may be a useful non-invasive test in confirming the presence of previously undiagnosed SOD. As SOD can be easily treated with EST, updating the current diagnostic criteria to include such types of SOD should be considered in the future.

The unknown and misunderstood life of Ruggero Oddi, the pioneer of biliary system physiology.

Ruggero Oddi was a talented scientist who initiated the modern era of biliary system physiology, not only with the anatomical discovery of the hepatopancreatic sphincter, but also with the detailed description of its spinal center and nerve regulation. However, his personal and scientific life were determined by an incredible series of unfortunate circumstances. Until now most of these events have been unknown, while the few known have produced biographies distorted by fake interpretations. The purpose of this article is to document Oddi's biography and scientific production in detail, comprehensively framing the scientific environment in which his discoveries occurred. It clears many misinterpretations about events in Oddi's life and academic career, bringing to a new light his figure as scientist in gastroenterological field.

Dysfunction of Biliary Sphincter of Oddi-Clinical, Diagnostic and Treatment Challenges.

Biliary Sphincter of Oddi dysfunction (SOD) is one of the main causes of post-cholecystectomy pain. In this review, we aimed to provide an update on the current knowledge on biliary SOD, with an emphasis on diagnostics and therapy. Overall, current but scarce data support biliary sphincterotomy for patients with type 1 and 2 SOD, but not for type 3. However, sphincterotomy is associated with post-treatment pancreatitis rates of from 10% to 15%, thus calling for improved diagnostics, patient selection and treatment modalities for SOD. The role of pharmacologic therapy for patients with SOD is poorly explored and only two randomized controlled trials are available. Currently, studies comparing treatment outcomes are few. There is an unmet need for randomized sham/placebo-controlled clinical trials related to both pharmacological and non-pharmacological treatments of SOD.

Sphincter of Oddi incompetence associated with duodenal stenosis in a newborn: A case report.

Newborn incompetence of the sphincter of Oddi is rare. While there are many causes of reflux of air or ingested contrast material into the biliary tree in adults, in the newborn, it is usually due to incompetence of the sphincter of Oddi associated with partial or complete duodenal obstruction. This paper presents upper gastrointestinal series findings of incompetence of the sphincter of Oddi associated with duodenal stenosis in a 3-day-old newborn. If pneumobilia is identified in the newborn, although the possibility is low, clinicians should consider incompetence of the sphincter of Oddi with duodenal obstruction as well as portal vein gas.