Endoscopic Retrograde Cholangiopancreatography Under General Anesthesia Compared to Conscious Sedation Study.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is used to diagnose and treat pancreatic and biliary disease. The current standard is to conduct ERCP under conscious sedation (CS). Patient movement and agitation during ERCP under CS can result in procedure failure and complications. Aiming to reduce procedure failure rates and complications, Kelowna General Hospital (KGH) in British Columbia, Canada transitioned to performing ERCP under general anesthesia (GA) as the practice standard. Objective: To determine if conducting ERCP under GA compared to CS decreases procedure complications, particularly post-ERCP pancreatitis (PEP). Methods: The charts of 2,198 patients who underwent ERCP at KGH between 2015 and 2020 were reviewed. Before September 17, 2017, ERCP was performed under CS (n = 1,316). Afterwards, ERCP was conducted under GA (n = 882). Demographic, clinical, and procedural data were extracted. The data were analyzed using univariate and multivariate statistical analysis. Results: Procedure failure rates (CS = 9 percent, GA = 3 percent, P < 0.001) decreased in the GA cohort after adjusting for age, sex, and co-morbidities. Thirty-day mortality, intensive care unit (ICU) transfer, returns post-discharge, PEP, and cholangitis rates were similar between cohorts. Conclusion: Performing ERCP under GA compared to CS resulted in an increase in procedural success rates. Other complication rates were similar between groups.

Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer.

In carcinogenesis, the "field defect" is recognized clinically because of the high propensity of survivors of certain cancers to develop other malignancies of the same tissue type, often in a nearby location. Such field defects have been indicated in colon cancer. The molecular abnormalities that are responsible for a field defect in the colon should be detectable at high frequency in the histologically normal tissue surrounding a colonic adenocarcinoma or surrounding an adenoma with advanced neoplasia (well on the way to a colon cancer), but at low frequency in the colonic mucosa from patients without colonic neoplasia. Using immunohistochemistry, entire crypts within 10 cm on each side of colonic adenocarcinomas or advanced colonic neoplasias were found to be frequently reduced or absent in expression for two DNA repair proteins, Pms2 and/or ERCC1. Pms2 is a dual role protein, active in DNA mismatch repair as well as needed in apoptosis of cells with excess DNA damage. ERCC1 is active in DNA nucleotide excision repair. The reduced or absent expression of both ERCC1 and Pms2 would create cells with both increased ability to survive (apoptosis resistance) and increased level of mutability. The reduced or absent expression of both ERCC1 and Pms2 is likely an early step in progression to colon cancer. DNA repair gene Ku86 (active in DNA non-homologous end joining) and Cytochrome c Oxidase Subunit I (involved in apoptosis) had each been reported to be decreased in expression in mucosal areas close to colon cancers. However, immunohistochemical evaluation of their levels of expression showed only low to modest frequencies of crypts to be deficient in their expression in a field defect surrounding colon cancer or surrounding advanced colonic neoplasia. We show, here, our method of evaluation of crypts for expression of ERCC1, Pms2, Ku86 and CcOI. We show that frequency of entire crypts deficient for Pms2 and ERCC1 is often as great as 70% to 95% in 20 cm long areas surrounding a colonic neoplasia, while frequency of crypts deficient in Ku86 has a median value of 2% and frequency of crypts deficient in CcOI has a median value of 16% in these areas. The entire colon is 150 cm long (about 5 feet) and has about 10 million crypts in its mucosal layer. The defect in Pms2 and ERCC1 surrounding a colon cancer thus may include 1 million crypts. It is from a defective crypt that colon cancer arises.

Pathogenesis of portal hypertensive gastropathy: translating basic research into clinical practice.

Portal hypertensive gastropathy (PHG) is often seen in patients with portal hypertension, and can lead to transfusion-dependent anemia as well as acute, life-threatening bleeding episodes. This Review focuses on the mechanisms that underlie the pathogenesis of PHG that provide reasonable grounds for the treatment of this condition, and ultimately enable translation of basic research into clinical practice. Increased portal pressure associated with cirrhosis and liver dysfunction is critical for the development of clinically significant PHG, and leads to impaired gastric mucosal defense mechanisms that render the stomach susceptible to mucosal injury. The use of pharmacological agents such as beta-blockers reduces the frequency of bleeding episodes in PHG. As a last resort, surgical decompression of the portal system, transjugular intrahepatic stent placement and liver transplantation can resolve this condition. Elimination of known risk factors for gastric injury such as alcohol, aspirin and traditional NSAIDs is critical. The role of Helicobacter pylori colonization of the gastric mucosa in PHG is not clear. Careful and critical interpretation of human and experimental data can be helpful to establish a rationale for the medical management of this important condition.

Changing epidemiology and risk factors for gastrointestinal non-Hodgkin's lymphoma in a North American population: population-based study.

OBJECTIVES: To assess the incidence, risk factors, and endoscopic presentation of gastrointestinal non-Hodgkin's lymphoma (GI NHL) in a large predominantly urban adult population sample. METHODS: A comprehensive database review of all diagnoses of GI NHL in the Calgary Health Region over a 5-yr period (1999-2003) was undertaken. Longer-term data from a population-based HIV database (1985-2004) were also reviewed. A regional pathology database was used to corroborate case identification. All patients 18 yr of age or older were included. Age- and gender-adjusted incidence rates were calculated. Within the HIV-positive population, incidence rates were compared over time. Endoscopic appearances were assessed and compared. RESULTS: Fifty-six GI NHL cases occurred during the study period. The age- and gender-adjusted annual incidence of GI NHL was 1.73 per 100,000 in the study population. The majority were diffuse large B-cell histology (54%), followed by lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) (29%). Increasing age, history of kidney transplant, and H. pylori positivity in MALT lymphoma were identified as risk factors. Within the HIV-positive population, a highly significant drop in GI NHL was seen over time, with an incidence of 3.86 per 1,000 patient-years in 1985-1989 compared to zero cases in 2000-2004, despite a greater prevalence of HIV disease (P < 0.0001 for trend). MALT lymphoma was less likely to manifest as a mass on endoscopy versus other presentations (P < 0.05). CONCLUSIONS: Population-based GI NHL incidence rates in Calgary are higher than those described elsewhere in North America or in Britain. The incidence of GI NHL within the HIV population has virtually disappeared, presumably due to the advent of highly active retroviral therapy.

Utility of endoscopic ultrasound, cytology and fluid carcinoembryonic antigen and CA 19-9 levels in pancreatic cystic lesions.

AIM: To assess the diagnostic accuracy of endoscopic ultrasound (EUS), fluid tumor markers and cytology in distinguishing benign from (pre)malignant pancreatic cystic lesions. METHODS: 46 consecutive patients, referred to a gastroenterologist and surgeon for a symptomatic or incidental pancreatic cyst, were reviewed. EUS, cytology, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) levels were compared with the final diagnosis, based on surgical pathology and/or imaging follow-up of at least 12 mo. Cysts were classified as benign (pseudocyst, serous cystadenoma) or malignant/pre-malignant (mucinous cystic neoplasm). Receiver-operator characteristics (ROC) curve analysis was performed. RESULTS: The mean age was 56 years; 29% were male and median cyst diameter was 3 cm. Final outcome was obtained in 41 (89%) patients. Twenty-three (56%) of these 41 had surgical pathology. Twenty-three (56%) had benign lesions and 18 (44%) had malignant/pre-malignant lesions. Sensitivity, specificity and positive and negative predictive value of EUS alone to distinguish benign from malignant/premalignant pancreatic cystic lesions were 50%, 56%, 36% and 54% and for cytology were 71%, 96%, 92% and 85%, respectively. The corresponding values for the ROC-derived ideal cutoffs were 75%, 90%, 75%, 90% for CA 19-9 (> 37 U/mL) and 70%, 85%, 79% and 78% for CEA (> 3.1 ng/mL). Subgroup analysis of those with surgical pathology yielded almost identical performance and cutoffs. CONCLUSION: Cytology and cyst fluid tumor marker analysis is a very useful tool in distinguishing benign from (pre)malignant pancreatic cystic lesions.

Roles of platelets and proteinase-activated receptors in gastric ulcer healing.

Proteinase-activated receptors (PARs) are expressed on the surface of many cells, but those on the platelet have been among the most thoroughly characterized. PARs act as key receptors mediating the proaggregatory and pro-secretory effects of thrombin. In addition to contributing to hemostasis, platelets are increasingly being viewed as important contributors to healing and to tumor growth. This is attributable to the many pro- and anti-angiogenic factors that are stored within platelets, which can be released at the sites of injury and new vessel growth. In this paper, we review the importance of the platelet in gastric ulcer healing, the contribution of platelet-contained angiogenic factors to the healing of gastric ulcers, and the role of PARs in regulating the release of angiogenic factors from platelets. Taken together, our results suggest that PARs, including those expressed on platelets, are a rational therapeutic target for modulating healing processes and tumor growth.

Isolated right segmental hepatic duct injury following laparoscopic cholecystectomy.

PURPOSE: Laparoscopic cholecystectomy (LC) is the treatment of choice for gallstones. There is an increased incidence of bile duct injuries in LC compared with the open technique. Isolated right segmental hepatic duct injury (IRSHDI) represents a challenge not only for management but also for diagnosis. We present our experience in the management of IRSHDI, with long-term follow-up after treatment by a multidisciplinary approach. METHODS: Twelve consecutive patients (9 women, mean age 48 years) were identified as having IRSHDI. Patients' demographics, clinical presentation, management and outcome were collected for analysis. The mean follow-up was 44 months (range 2-90 months). RESULTS: Three patients had the LC immediately converted to open surgery without repair of the biliary injury before referral. Treatments before referral included endoscopic retrograde cholangiopancreatography (ERCP), percutaneous drainage and surgery, isolated or in combination. The median interval from LC to referral was 32 days. Eleven patients presented with biliary leak and biloma, one with obstruction of an isolated right hepatic segment. Post-referral management of the biliary lesion used a combination of ERCP stenting, percutaneous drainage and stent placement and surgery. In 6 of 12 patients ERCP was the first procedure, and in only one case was IRSHDI identified. In 6 patients, percutaneous transhepatic cholangiography (PTC) was performed first and an isolated right hepatic segment was demonstrated in all. The final treatment modality was endoscopic management and/or percutaneous drainage and stenting in 6 patients, and surgery in 6. The mean follow-up was 44 months. No mortality or significant morbidity was observed. CONCLUSION: Successful management of IRSHDI after LC requires adequate identification of the lesion, and multidisciplinary treatment is necessary. Half of the patients can be treated successfully by nonsurgical procedures.

Post-sphincterotomy bleeding after the introduction of microprocessor-controlled electrosurgery: does the new technology make the difference?

BACKGROUND: Bleeding as a complication of endoscopic sphincterotomy is influenced by several factors. The objective of this study was to compare rates of bleeding after sphincterotomy performed with two different electrosurgical current generators (Valleylab SSE2L and ERBE ICC200). METHODS: A total of 6179 consecutive reports of ERCP were analyzed to compare the frequency of endoscopically and clinically evident bleeding after sphincterotomy when using the Valleylab SSE2L generator (from February 1994 to November 1997) and the ERBE ICC200 generator (from December 1997 to September 2000). Relevant risk factors were assessed by univariate analysis and significant predictors were included in a multiple logistic regression model. RESULTS: A total of 2711 sphincterotomies were performed in 2309 patients (1749 biliary, 962 pancreatic). Endoscopically observed bleeding occurred in 68 patients (5.5%) in the ValleyLab group and 13 (1.2%) in the ERBE group. The ValleyLab generator was independently associated with an increase in endoscopically observed bleeding (OR 4.02: 95% CI[2.13, 7.61], p <0.001). There was no significant difference in clinically evident bleeding between the two groups. CONCLUSIONS: Use of the microprocessor-controlled ERBE electrosurgical generator for endoscopic sphincterotomy was associated with a significantly lower frequency of endoscopically observed bleeding but not clinically evident bleeding.

Proteinase-activated receptors 1 and 4 counter-regulate endostatin and VEGF release from human platelets.

The roles of proteinase-activated receptors (PARs) in platelet functions other than aggregation are not well understood. Among these is the release of factors that regulate the process of angiogenesis, such as endostatin and VEGF, which, respectively, inhibit and promote angiogenesis. PAR1 and PAR4 are expressed on the surface of human platelets and can be activated by thrombin. In the present study, we have attempted to determine the roles of PAR1 and PAR4 in regulating release of endostatin and VEGF from human platelets. Aggregation and endostatin release could be elicited by a specific PAR4 agonist (AYPGKF-NH(2)). The PAR4 agonist concentration dependently suppressed VEGF release. A selective PAR1 agonist (TFLLR-NH(2)) induced platelet aggregation and VEGF release but suppressed endostatin release. Thrombin did not affect endostatin or VEGF release. However, in the presence of a selective PAR1 antagonist (SCH79797), thrombin stimulated endostatin release and suppressed VEGF release. Conversely, in the presence of a selective PAR4 antagonist (transcinnamoyl-YPGKF-NH(2)), thrombin stimulated VEGF release. In vivo, treatment of rats with established gastric ulcers with a PAR1 antagonist each day for 1 wk resulted in a significant retardation of healing. We conclude that PAR1 and PAR4 counter-regulate the release of endostatin and VEGF from platelets. These protease-activated receptors could therefore play a crucial role in regulating angiogenesis and in turn could regulate the processes of wound healing and tumor growth.

Mechanisms of nonsteroidal anti-inflammatory drug-induced gastrointestinal injury and repair: a window of opportunity for cyclooxygenase-inhibiting nitric oxide donors.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause damage in the upper gastrointestinal (GI) tract by impairing the ability of the mucosa to resist and respond to injury. Many of these effects of NSAIDs can be attributed to their ability to suppress mucosal prostaglandin synthesis. Selective inhibitors of cyclooxygenase (COX)-2 are less likely to disrupt mucosal defence and do not interfere with platelet aggregation. Thus, their use is associated with a reduced incidence of serious GI adverse events; however, a significant risk of such events still persists. At least in animal models, selective COX-2 inhibitors interfere with ulcer healing to the same extent as conventional NSAIDs. In contrast, COX-inhibiting nitric oxide donors (CINODs) produce anti-inflammatory and analgesic effects comparable or superior to those of NSAIDs, but with greatly reduced GI toxicity. Unlike NSAIDs and selective COX-2 inhibitors, CINODs do not interfere with ulcer healing. Moreover, because CINODs suppress the activity of both COX-1 and COX-2, they do not share with selective COX-2 inhibitors the lack of cardioprotection afforded by significant suppression of platelet aggregation. Because of their safety profile, CINODs may be particularly useful for long term prevention applications, such as for colon cancer, cardiovascular disease and Alzheimer's disease.

Mucosal repair and COX-2 inhibition.

The healing of gastric ulcer is a complicated process that involves the proliferation of epithelial and endothelial cells and the concerted actions of a wide range of growth factors. Prostaglandins play an important role in ulcer healing. Expression of cyclooxygenase-2 (COX-2) is markedly upregulated around the margins of gastric ulcers and its inhibition leads to a delay of ulcer healing. Several of the growth factors that promote ulcer healing may work in part through COX-2-dependent mechanisms. Angiogenesis, which is crucial to ulcer healing, is tightly regulated by growth factors. Treatment with selective COX-2 inhibitors appears to alter the balance of serum levels of growth factors, favoring an inhibition of angiogenesis. Given the importance of COX-2 in regulating ulcer healing, caution should be taken in the use of selective inhibitors of COX-2 by patients at risk of ulcer disease.