Rome IV. Gallbladder and Sphincter of Oddi Disorders.

The concept that motor disorders of the gallbladder, cystic duct and sphincter of Oddi can cause painful syndromes is attractive and popular, at least in the USA. However, the results of commonly performed ablative treatments (cholecystectomy and sphincterotomy) are not uniformly good. The predictive value of tests that are often used to diagnose dysfunction (dynamic gallbladder scintigraphy and sphincter manometry) is controversial. Evaluation and management of these patients is made difficult by the fluctuating symptoms and the placebo effect of invasive interventions. A recent stringent study has shown that sphincterotomy is no better than sham treatment in patients with post-cholecystectomy pain and little or no objective abnormalities on investigation, so that the old concept of sphincter of Oddi dysfunction (SOD) type III is discarded. ERCP approaches are no longer appropriate in that context. There is a pressing need for similar prospective studies to provide better guidance for clinicians dealing with these patients. We need to clarify the indications for cholecystectomy in patients with Functional Gallbladder Disorder (FGBD) and the relevance of sphincter dysfunction in patients with some evidence for biliary obstruction (previously SOD type II, now called "Functional Biliary Sphincter Disorder - FBSD") and with idiopathic acute recurrent pancreatitis.

Gadolinium as an alternative contrast agent for therapeutic ERCP in the iodine-allergic patient.

Performance of endoscopic retrograde cholangiopancreatography (ERCP) requires an intraductal contrast agent. The contrast of choice is an iodine-based agent. The alternatives in patients with a severe allergy to iodinated contrast are limited. We undertook a retrospective review of the success and safety of gadolinium as an alternative radiocontrast agent in patients with allergy to iodine-based contrast in a series of five patients in a tertiary care pancreaticobiliary referral center. The five patients underwent a total of six ERCP procedures using a gadolinium chelate as the radiocontrast agent. ERCP was technically successful in all cases, including pancreatic endotherapy. There were no contrast-related adverse reactions. Gadolinium is concluded to be a reasonable alternative to iodine-based ERCP contrast in selected patients. It provides inferior image quality compared to standard iodine-based contrast but was not technically limiting in our small experience.

The revised Atlanta criteria more accurately reflect severity of post-ERCP pancreatitis compared to the consensus criteria.

Background and objective: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most prevalent complication after ERCP with an incidence of 3.5%. PEP severity is classified according to either the consensus criteria or the revised Atlanta criteria. In this international cohort study we investigated which classification is the strongest predictor of PEP-related mortality. Methods: We reviewed 13,384 consecutive ERCPs performed between 2012 and 2017 in eight hospitals. We gathered data on all pancreatitis-related adverse events and compared the predictive capabilities of both classifications. Furthermore, we investigated the correlation between the two classifications and identified reasons underlying length of stay. Results: The total sample consisted of 387 patients. The revised Atlanta criteria have a higher sensitivity (100 vs. 55%), specificity (98 vs. 72%) and positive predictive value (58 vs. 5%). There is a significant difference (p < 0.001) between the two classifications. In 124 patients (32%), the length of stay was influenced by concomitant diseases. Conclusion: The revised Atlanta classification is superior in predicting mortality and better reflects PEP severity. This has important implications for researchers, clinicians and patients. For the diagnosis of PEP pancreatitis, the consensus criteria remain the golden standard. However, the revised Atlanta criteria are preferable for defining PEP severity.

Small prophylactic pancreatic duct stents: an assessment of spontaneous passage and stent-induced ductal abnormalities.

BACKGROUND AND STUDY AIMS: Placing small stents in the pancreatic duct at endoscopic retrograde cholangiopancreatography reduces the risk of pancreatitis. However, this practice means that a second procedure might be required to remove the stent, and stents can also damage the duct. The aims of this study were to determine the frequency of spontaneous dislodgment and to assess the incidence of stent-induced ductal irregularities. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive patients seen over a 3-year period (2001 - 2004) who had undergone placement of a 3-Fr pancreatic duct stent and in whom the fate of the stent had been documented. Radiographs were reviewed to determine stent passage at 30 days. If applicable, follow-up pancreatograms were reviewed to assess for stent-induced ductal abnormalities. Statistical analysis was performed using chi-squared and Fisher's exact tests for proportions, and 95 % binomial confidence intervals (CI) were calculated. RESULTS: Records for 125 consecutive patients who had had 3-Fr pancreatic stents placed were reviewed. The stents had passed spontaneously within 30 days in 110/125 patients (88 %). In the remaining 15 patients (12 %, 95 % CI 6.9 % - 19 %), the stents were still present on follow-up radiographs after a median time of 36 days, (range 31 - 116 days). Stent length, pancreatic sphincterotomy, and pancreas divisum had no effect on the likelihood of spontaneous passage. No stent-induced ductal irregularities were observed. CONCLUSIONS: Nearly 90 % of prophylactic 3-Fr pancreatic duct stents pass spontaneously within 30 days, and these stents were not observed to induce changes in the pancreatic duct.

Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia.

BACKGROUND AND STUDY AIMS: The most permanent method of treating achalasia is a surgical myotomy. Because of the requirement for a mucosal incision and the risk of perforation, this procedure has not generally been approached endoscopically. We hypothesized that we could perform a safe and robust myotomy by working in the submucosal space, accessed from the esophageal lumen. MATERIALS AND METHODS: Four pigs were used for this experiment. Baseline lower esophageal sphincter (LES) pressures were recorded and the pigs underwent upper endoscopy using a standard endoscope. A submucosal saline lift was created approximately 5 cm above the LES and a small nick was made in the mucosa in order to facilitate the introduction of a dilating balloon. After dilation, the scope was introduced over the balloon into the submucosal space and advanced toward the now visible fibers of the LES. The circular layer of muscle was then cleanly incised using an electrocautery knife in a distal-to-proximal fashion, without complications. The scope was then withdrawn back into the lumen and the mucosal defect was closed with endoscopically applied clips. The entire procedure took less than 15 minutes. Manometry was repeated on day 5 after the procedure and the animals were euthanized on day 7. RESULTS: LES pressures fell significantly from an average of 16.4 mm Hg to an average of 6.7 mm Hg after the myotomy. The necropsy examinations revealed no evidence of mediastinitis or peritonitis. CONCLUSIONS: Endoscopic submucosal esophageal myotomy is feasible, safe, and effective in the short term. It has the potential for being useful in patients with achalasia. The submucosal space is a novel and potentially important field of operation for endoscopic procedures.

Peroral transgastric endoscopic primary repair of a ventral hernia in a porcine model.

BACKGROUND AND STUDY AIMS: Multiple studies have demonstrated the feasibility of peroral transgastric endoscopic procedures in animal models. The aim of the study was to evaluate the feasibility of a peroral transgastric endoscopic approach to repair abdominal wall hernias. PATIENTS AND METHODS: We performed acute experiments under general anesthesia with endotracheal intubation using 50-kg pigs. Following peroral intubation an incision of the gastric wall was made and the endoscope was advanced into the peritoneal cavity. An internal anterior abdominal wall incision was performed with a needle knife to create an animal model of a ventral hernia. After hernia creation an endoscopic suturing device was used for primary repair of the hernia. After completion of the hernia repair the endoscope was withdrawn into the stomach and the gastric wall incision was closed with endoscopic clips. Then the animals were killed for necropsy. RESULTS: Two acute experiments were performed. Incision of the gastric wall was easily achieved with a needle knife and a pull-type sphincterotome. A large (3 x 2 cm) defect of the abdominal wall (ventral hernia model) was closed with five or six sutures using the endoscopic suturing device. Postmortem examination revealed complete closure of the hernia without any complications. CONCLUSIONS: Transgastric endoscopic primary repair of ventral hernias in a porcine model is feasible and may be technically simpler than laparoscopic surgery.

Preliminary pneumoperitoneum facilitates transgastric access into the peritoneal cavity for natural orifice transluminal endoscopic surgery: a pilot study in a live porcine model.

BACKGROUND AND STUDY AIMS: Safe entrance into the peritoneal cavity through the gastric wall is paramount for the successful clinical introduction of natural orifice transluminal endoscopic surgery (NOTES). The aim of the study was to develop alternative safe transgastric access to the peritoneal cavity. PATIENTS AND METHODS: We performed 11 survival experiments on 50-kg pigs. In sterile conditions, the abdominal wall was punctured with a Veress needle. The peritoneal cavity was insufflated with 2 L carbon dioxide (CO (2)). A sterile endoscope was introduced into the stomach through a sterile overtube; the gastric wall was punctured with a needle-knife; after balloon dilation of the puncture site, the endoscope was advanced into the peritoneal cavity. Peritoneoscopy with biopsies from abdominal wall, liver and omentum, was performed. The endoscope was withdrawn into the stomach. The animals were kept alive for 2 weeks and repeat endoscopy was followed by necropsy. RESULTS: The pneumoperitoneum, easily created with the Veress needle, lifted the abdominal wall and made a CO (2)-filled space between the stomach and adjacent organs, facilitating gastric wall puncture and advancement of the endoscope into the peritoneal cavity. There were no hemodynamic changes or immediate or delayed complications related to pneumoperitoneum, transgastric access, or intraperitoneal manipulations. Follow-up endoscopy and necropsy revealed no problems or complications inside the stomach or peritoneal cavity. CONCLUSIONS: Creation of a preliminary pneumoperitoneum with a Veress needle facilitates gastric wall puncture and entrance into the peritoneal cavity without injury to adjacent organs, and can improve the safety of NOTES.

A new stapler-based full-thickness transgastric access closure: results from an animal pilot trial.

BACKGROUND AND STUDY AIMS: Reliable closure of the transluminal incision is the crucial step for natural orifice transluminal endoscopic surgery (NOTES) procedures. The aim of this study was to evaluate the feasibility and effectiveness of transgastric access closure with a flexible stapling device in a porcine survival model. PATIENTS AND METHODS: We carried out four experiments (two sterile and two nonsterile) on 50 kg pigs. The endoscope was passed through a gastrotomy made with a needle knife and an 18-mm controlled radial expansion dilating balloon. After peritoneoscopy, a flexible linear stapling device (NOLC60, Power Medical Interventions, Langhorne, Pennsylvania, USA) was perorally advanced over a guide wire into the stomach, positioned under endoscopic guidance, and opened to include the site of gastrotomy between its two arms; four rows of staples were fired. One animal was sacrificed 24 hours after the procedure (progression of pre-existing pneumonia). The remaining animals were survived for 1 week and then underwent repeat endoscopy and postmortem examination. RESULTS: Peroral delivery and positioning of the stapling device involved some technical difficulties, mostly due to the short length (60 cm) of the stapling device. The stapler provided complete leak-resistant gastric closure in all pigs. None of the surviving animals had any clinical signs of infection. Necropsy demonstrated an intact staple line with full-thickness healing of the gastrotomy in all animals. Histologic examination confirmed healing, but also revealed intramural micro-abscesses within the gastric wall after nonsterile procedure. CONCLUSIONS: Gastrotomy closure with a perorally delivered flexible stapling device created a leak-resistant transmural line of staples followed by full-thickness healing of the gastric wall incision. Increasing the length of the instrument and adding device articulation will further facilitate its use for NOTES procedures.

Do all patients with abnormal intraoperative cholangiogram merit endoscopic retrograde cholangiopancreatography?

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used for postoperative evaluation of an abnormal intraoperative cholangiogram (IOC). Although a normal IOC is very suggestive of a disease-free common bile duct (CBD), abnormal studies are associated with high false-positive rates. This study aimed to identify a subset of patients with abnormal IOC who would benefit from a postoperative ERCP. METHODS: This prospective study investigated 51 patients with abnormal IOC at laparoscopic cholecystectomy who underwent postoperative ERCP at two tertiary referral centers over a 3-year period. Univariate and multivariate logistic regression analyses were performed to determine predictors of CBD stones at postoperative ERCP. RESULTS: For all 51 patients, ERCP was successful. The ERCP showed CBD stones in 33 cases (64.7%), and normal results in 18 cases (35.2%). On univariate analysis, abnormal liver function tests (p < 0.0001) as well as IOC findings of a large CBD stone (p = 0.03), multiple stones (p = 0.01), and a dilated CBD (p = 0.07) predicted the presence of retained stones at postoperative ERCP. However, on multivariable analysis, only abnormal liver function tests correlated with the presence of CBD stones (p < 0.0001). CONCLUSIONS: One-third of patients with an abnormal IOC have a normal postoperative ERCP. Elevated liver function tests can help to identify patients who merit further evaluation by ERCP. The use of less invasive methods such as endoscopic ultrasound or magnetic resonance cholangiopancreatography should be considered for patients with normal liver function tests to minimize unnecessary ERCPs.

Transgastric endoscopic splenectomy: is it possible?

BACKGROUND: We have previously reported the feasibility of diagnostic and therapeutic peritoneoscopy including liver biopsy, gastrojejunostomy, and tubal ligation by an oral transgastric approach. We present results of per-oral transgastric splenectomy in a porcine model. The goal of this study was to determine the technical feasibility of per-oral transgastric splenectomy using a flexible endoscope. METHODS: We performed acute experiments on 50-kg pigs. All animals were fed liquids for 3 days prior to procedure. The procedures were performed under general anesthesia with endotracheal intubation. The flexible endoscope was passed per orally into the stomach and puncture of the gastric wall was performed with a needle knife. The puncture was extended to create a 1.5-cm incision using a pull-type sphincterotome, and a double-channel endoscope was advanced into the peritoneal cavity. The peritoneal cavity was insufflated with air through the endoscope. The spleen was visualized. The splenic vessels were ligated with endoscopic loops and clips, and then mesentery was dissected using electrocautery. RESULTS: Endoscopic splenectomy was performed on six pigs. There were no complications during gastric incision and entrance into the peritoneal cavity. Visualization of the spleen and other intraperitoneal organs was very good. Ligation of the splenic vessels and mobilization of the spleen were achieved using commercially available devices and endoscopic accessories. CONCLUSIONS: Transgastric endoscopic splenectomy in a porcine model appears technically feasible. Additional long-term survival experiments are planned.

Carcinoid tumour of stomach and primary hyperparathyroidism: a new association.

Three cases of carcinoid tumour of the stomach associated with primary hyperparathyroidism had the clinical and pathological features of a pluriglandular syndrome. Two of the patients showed multiple small polypoid carcinoids in the non-antral stomach, in conjunction with a parathyroid adenoma in one and parathyroid hyperplasia in the other case. One of these patients was also suffering from pernicious anaemia. A third patient had a large metastasising carcinoid arising in the gastric body and a parathyroid adenoma. Immunohistochemical stains for PGP 9.5 were positive in the carcinoids of all three cases. In all cases the carcinoids showed immunoreactivity for gastrin. A positive family history of endocrine hyperplasia and neoplasia was established in one case. It is suggested that patients with gastrointestinal carcinoids and their families should be evaluated for hyperparathyroidism, and patients with hyperparathyroidism presenting with upper gastrointestinal symptoms should undergo endoscopy to rule out gastric carcinoid tumours.

Duodenoscopic sphincterotomy for removal of bile duct stones in patients with gallbladders.

Duodenoscopic sphincterotomy was attempted in 71 elderly patients with gallbladders who presented with acute symptoms caused by common bile duct stones. Sphincterotomy was possible in all but one patient, and duct clearance was achieved in 61 (86%); failures were usually due to the size of the stones. Two patients required blood transfusions for immediate bleeding, and two underwent cholecystectomy for acute cholecystitis developing within 7 days of sphincterotomy. One patient with a retained stone was judged to be unfit for surgery and died 6 weeks after sphincterotomy. Eleven patients had elective cholecystectomy. Forty-eight patients (mean age 75 years) were discharged with their gallbladders in place; clinical follow-up (mean 19 months) had been possible in 44. None have suffered cholangitis or jaundice, and only five have so far needed cholecystectomy for recurrent biliary pains. Duodenoscopic sphincterotomy is recommended for acutely ill patients with symptoms caused by duct stones, even patients with gallbladders. Longer follow-up is required to judge the indications for subsequent cholecystectomy, but present evidence suggests that it is reasonable to postpone cholecystectomy indefinitely for many elderly and frail patients.

A preliminary report: urgent duodenoscopic sphincterotomy for acute gallstone pancreatitis.

Eleven patients wtih gallstone-related acute pancreatitis underwent urgent duodenoscopy and diathermy sphincterotomy; six had stones impacted at the papilla of Vater, and the remainder had stones in the bile duct. One patient had a gallstone in the pancreatic duct. Endoscopic removal of the duct stones resulted in a prompt, persistent clinical and biochemical improvement, except in one patient who had been referred from another hospital with a pseudocyst 3 weeks after the onset of illness. Pancreatography results were remarkably normal in the remaining patients. Use of emergency biliary decompression in patients with acute gallstone-related pancreatitis remains controversial, and the indications need clarification. However our results justify further evaluation of duodenoscopic sphincterotomy as an alternative to surgery.

Endoscopic treatment of stomal stenosis after choledochoduodenostomy: preliminary report.

Stomal stenosis occurs rarely after choledochoduodenostomy and is usually corrected by surgical revision. We describe four patients treated by diathermy enlargement of the orifice at duodenoscopy. The results justify further evaluation of this technique in patients who are prohibitive surgical risks.

Recurrent pseudocysts and pancreatitis after trauma: a complication of pancreas divisum.

Two patients are described who developed pancreatitis and recurrent pseudocysts after minimal trauma. Both had the congenital anomaly of pancreas divisum, and neither responded to surgical therapy appropriate to patients with normal anatomy. Both patients eventually required excision of the entire dorsal portion of the pancreas for relief. Patients with pancreatitis and pseudocysts should undergo endoscopic pancreatography immediately before surgery to aid in the definition of appropriate surgical therapy.

Indications for and the technique of local resection of tumors of the papilla of Vater.

Local resection of tumors of the papilla of Vater was performed in six cases (three benign adenomas and three adenocarcinomas). Pathology was suggested in all cases by endoscopic biopsy and confirmed by operative excision. A method of excision of the tumor and reconstruction of the pancreaticobiliary apparatus was used that eliminated all gross and microscopic disease. Only one of the patients with benign disease (familial polyposis) suffered from local recurrence. All three patients with malignant tumors developed local recurrences within 2 years of resection. Local resection seems to be a viable alternative to Whipple's resection in patients with benign tumors. In malignant cases, local resection should be considered only a palliative procedure and confined to elderly patients with severe concomitant disease and patients in whom a more radical procedure would incur an undue surgical risk.

Increased transforming growth factor beta in pure pancreatic juice in pancreatitis.

Cytokines play an important role in the regulation of inflammation and fibrosis in the development of chronic pancreatitis. In this study, transforming growth factor beta (TGFbeta), interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFalpha) were measured in pure pancreatic juice obtained through pancreatic duct cannulation. Twenty patients with chronic pancreatitis were compared with six patients thought to be free of pancreatic disease who were undergoing endoscopic retrograde cholangiopancreatography for biliary tract disorders. TGFbeta was detected in 17 of 20 patients with chronic pancreatitis tested (85%), compared with only one patient in the control group (17%). There was no measurable amount of IL-10, IL-6, or TNFalpha in any of the pure pancreatic juice samples from any of the patients. These data indicate that TGFbeta may play an active role in the advancement of pancreatitis by causing local inflammation and inducing fibroblasts to secrete collagen. This finding may be relevant in the future for identifying patients whose conditions may advance to chronic pancreatitis, and blocking the effects of TGFbeta could have therapeutic effects.

Pancreatic duct dilatation after secretin stimulation in patients with pancreas divisum.

Pancreas divisum is the most common anatomical variant of pancreatic ductal anatomy. It has been suggested that obstruction at the accessory papilla in subjects with pancreas divisum can be assessed by measurement of ductal diameter by ultrasonic examination after a maximal secretory stimulus with i.v. secretin. We have prospectively assessed this test in 44 individuals; nine healthy controls, nine patients with abdominal pain and normal pancreatic anatomy, 17 patients with pancreas divisum and abdominal pain but no other evidence of pancreatitis, and nine patients with pancreas divisum and either chronic or recurrent acute pancreatitis. We have found no correlation between ductal anatomy and response to i.v. secretin. Secretin provocation tests do not indicate which patients have accessory papillary stenosis and do not add support to the hypothesis of obstruction leading to pancreatitis in patients with pancreas divisum.

Radiologic pitfalls in endoscopic retrograde pancreatography.

Endoscopic pancreatography (ERCP) is currently the least invasive technique for obtaining detailed images of the pancreatic ductal system. Although expert ERCP is now an acceptably safe procedure, interpretation of endoscopic pancreatograms may be difficult, and misdiagnosis is still a risk to the patient. We have been able to divide misinterpretations into three broad categories: technical error, anatomic variation, and unusual images due to disease. Examples of each of these classifications are presented and discussed in hopes of decreasing the incidence of misdiagnosis.