Mohamed O. Othman

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in 2011, a Western perspective

Endoscopic mucosal resection (EMR) has become the standard of care for removal of large flat and sessile neoplastic lesions of the GI tract. Recently, endoscopic submucosal dissection (ESD) was introduced in Japan as an alternative technique, which allows en bloc resection of large lesions. The applications of EMR and ESD are expanding and many Western endoscopists are adopting these techniques. Paris classification and Kudo pit pattern classification allows prediction of the depth of invasion of early neoplastic lesions and thus, avoids resection of lesions invading the deep submucosa which have higher rates of lymphatic spread. ESD of early stomach cancer is the standard of care in Japan. Recent published reports from Western countries showed comparable results for ESD of early gastric cancers to those done in Japan. Recently, EMR combined with ablation has been used frequently in Western countries for treatment of high-grade dysplasia in early adenocarcinoma of the esophagus. Although ESD of early neoplastic lesions of the esophagus is technically difficult, few promising reports were published proving the feasibility of this technique in the West. ESD has been shown to achieve higher en bloc resection and lower rates of tumour recurrence in removal of lateral spreading colonic polyps. A hybrid technique of circumferential submucosal incision followed by en bloc EMR has been used for removal of large colonic lesions in some Western endoscopy centres. In Western countries, training for ESD is challenging given the lack of training in the relatively easier early gastric cancer lesions. Animal model training combined with observing experts in ESD could be an alternative for Western endoscopists. Inspite of obstacles, ESD applications are continuing to grow in Western countries.

Conservative management of cholelithiasis and its complications in pregnancy is associated with recurrent symptoms and more emergency department visits

BACKGROUND Pancreaticobiliary complications of gallstones are common in pregnancy and can result in serious sequelae. Previous studies have shown conflicting results regarding different approaches of treatment. OBJECTIVE To compare the outcomes of conservative treatment versus operative and endoscopic interventions in the management of complications related to gallstones during pregnancy. DESIGN Retrospective chart review. SETTING Tertiary-care referral facility. PATIENTS A total of 112 patients who had complications related to gallstones during pregnancy. INTERVENTION Patients were classified into 3 groups: conservative treatment, laparoscopic cholecystectomy (LC), and ERCP. MAIN OUTCOME MEASUREMENTS We collected demographic data and information regarding treatment complications and pregnancy outcomes. RESULTS A total of 112 pregnant patients met the inclusion criteria, with a mean age of 25 years. Main clinical presentations were biliary colic (n = 56), biliary pancreatitis (n = 27), acute cholecystitis (n = 17), and choledocholithiasis (n = 12). A total of 68 patients underwent conservative treatment, 13 patients underwent ERCP, 27 patients had LC, and 4 patients received both ERCP and LC. Recurrent biliary symptoms were significantly more common in patients who received conservative treatment (P = .0005). The number of emergency department visits was significantly higher in the conservative treatment group compared with the active intervention group (P = .0006). The number of hospitalizations also was higher in the conservative treatment group (P = .03). Fetal birth weight was similar in both groups (P = .1). Patients treated conservatively were more likely to undergo cesarean section operations for childbirth (P = .04). LIMITATIONS Single-center, retrospective study. CONCLUSION Conservative treatment of cholelithiasis and its complications during pregnancy is associated with recurrent biliary symptoms and frequent emergency department visits. ERCP and LC are safe alternative approaches during pregnancy.

Gastric polyps: Association with Helicobacter pylori status and the pathology of the surrounding mucosa, a cross sectional study.

AIM To assess the endoscopic characteristics of gastric polyps and their association with Helicobacter pylori (H. pylori) status in a predominantly Hispanic population. METHODS We conducted a retrospective study of all esophagogastroduodenoscopies performed at our institution. Demographic, endoscopic and histopathological data were reviewed. Categorization of patients into Hispanic and Non-Hispanic was based on self-identification. Patients without resection/biopsy were not included in the analysis. Identification of polyps type was based on histological examination. One way analysis of variance was used to compare continuous variables among different polyp types and Fishers exact test was used compare categorical variables among polyp types. Unadjusted and adjusted comparisons of demographic and clinical characteristics were performed according to the H. pylori status and polyp type using logistic regressions. RESULTS Of 7090 patients who had upper endoscopy, 335 patients had gastric polyps (4.7%). Resection or biopsy of gastric polyps was performed in 296 patients (88.4%) with a total of 442 polyps removed or biopsied. Of 296 patients, 87 (29%) had hyperplastic polyps, 82 (28%) had fundic gland polyps and 5 (1.7%) had adenomatous polyps. Hyperplastic polyps were significantly associated with positive H. pylori status compared with fundic gland polyps (OR = 4.621; 95%CI: 1.92-11.13, P = 0.001). Hyperplastic polyps were also found to be significantly associated with portal hypertensive gastropathy compared with fundic gland polyps (OR = 6.903; 95%CI: 1.41-33.93, P = 0.0174). Out of 296 patients, 30 (10.1%) had a follow-up endoscopy with a mean duration of 26 ± 16.3 mo. Interval development of cancer was not noted in any of the patients during follow up period. CONCLUSION Gastric hyperplastic polyps were significantly associated with positive H. pylori status and portal hypertensive gastropathy as compared with fundic gland polyps.

Bacteroides fragilis vertebral osteomyelitis: case report and a review of the literature.

Background: To review the presentation of Bacteroides fragilis (B fragilis) spondylodiscitis. Methods: Two investigators independently searched the published English, Spanish and French languages literature through September 2005 using MEDLINE (1966–2005). We included all reported cases of vertebral osteomyelitis or spondylodiscitis caused by B fragilis, not related to sacral decubitus ulcers, in adults (age 16 yr and above). A third author independently reviewed all articles and extracted data for accuracy. The final pool of eligible publications included 11 articles, publication dates ranging from 1978 to 2005. Eight were written in English, two in Spanish, and one in French. Results: The age of the patients in this series ranged from 17 to 74 years, with a mean age of 55 years. Male to female ratio was 6:1. Lumbar involvement was reported in nine cases, thoracic involvement in two patients and sacral involvement in one patient. B fragilis was recovered by blood culture in four patients and by tissue culture in eight patients. Metronidazole was the most common antibiotic used for treatment (eight patients), either as monotherapy or in combination with other antibiotics. Conclusions: B fragilis is a rare causative agent of spondylodiscitis, but it should be considered in patients with spondylodiscitis who have contiguous intraabdominal or pelvic infections or who had recent gastrointestinal procedures that may have led to B fragilis bacteremia.

The Role of Endoscopic Ultrasonography in the Diagnosis and Management of Pancreatic Cancer

EUS with FNA is highly sensitive and specific for diagnosing pancreatic cancer. However, in certain situations, such as in patients with chronic pancreatitis, this high sensitivity and specificity can significantly diminish. The use of new technology, such as EUS elastography, CE-EUS, and gene mutations detection in FNA specimens, can help to differentiate chronic pancreatitis from pancreatic cancer. EUS has evolved from a diagnostic procedure to a therapeutic intervention in pancreatic cancer. EUS-guided fiducial insertion and EUS-guided delivery of antitumor agents, in addition to celiac plexus neurolysis, are the main therapeutic applications of EUS in pancreatic cancer.

Carcino Embryonic Antigen and long-term follow-up of mucinous pancreatic cysts including intraductal papillary mucinous neoplasm

BACKGROUND AND AIMS The utility of Carcino Embryonic Antigen (CEA) in differentiating malignant from benign pancreatic cysts is controversial. We sought to examine the role of CEA in differentiating benign from malignant cysts and its utility in progression of cyst size in follow-up. METHODS Retrospective chart review of patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration for mucinous cysts between 1998 and 2010. CEA was measured in benign and malignant mucinous cysts. Coefficient of determination (R(2)) was used to measure the association between change in cyst size and CEA. Mann-Whitney test was used to compare the median values of CEA. RESULTS 143 patients (38.4% males) were included (mean age 68.9 ± 0.8 years). 105 patients had intra-cystic CEA measured. 63 patients underwent surgery while 80 patients were in the follow-up group. In the surgical group, median CEA value for benign and malignant mucinous neoplasms was 796 and 438 ng/ml, respectively (p=0.79). The median follow-up was 21 months. There was no correlation between CEA level and progression in cyst size in patients who had >6 months of follow-up, R(2)=0.0002. Malignant transformation was observed in 5 (5.9%) patients. CONCLUSION CEA level was not predictive of malignant cyst nor cyst size progression over follow-up.

Endoscopic mucosal resection recurrence rate for colorectal lesions.

Objectives We aimed to evaluate the polyp recurrence rate after endoscopic mucosal resection (EMR) and factors contributing to increased recurrence. Methods MEDLINE (from 1966 to 2013), the Cochrane Central Register of Controlled Trials, and the Scopus database were searched in December 2013. Studies evaluating the polyp recurrence rate after colonic EMR were included. All of the articles were assigned a quality score. Standard forms were used to extract data regarding study design, outcome measures, and adverse effects by two independent reviewers. We performed a meta-analysis with a random effects model. Separate analyses were performed for each main outcome by using odds ratio (OR) and risk difference. Heterogeneity was assessed by I2 measure of inconsistency. Results For the recurrence rate of colorectal lesions, 30 articles were included, with a total of 3404 patients. The polyp recurrence rate after EMR was 13.1%. Piecemeal resection was associated with a higher recurrence rate compared with en bloc resection (OR 4.39, 95% confidence interval 2.05–9.41; 14 studies). The use of argon plasma coagulation did not affect the polyp recurrence rate (OR 1.23, 95% confidence interval 0.39–3.88). Significant heterogeneity was present among studies. Conclusions The recurrence rate of colorectal polyps after EMR is reasonably low; however, piecemeal resection was associated with a higher recurrence rate than en bloc resection after EMR.

Confocal laser endomicroscopy: is it prime time?

Confocal laser endomicroscopy (CLE) is a novel imaging technology which utilizes focal laser illumination to scan one focal plane in the selected imaged lesion. This allows for a microscopic view of the surface epithelium and up to 250 mm of the lamina propria creating a ‘‘virtual biopsy’’ of the area of interest. To obtain a high contrast image, CLE requires contrast injection such as fluorescein. The contrast material diffuses through the capillaries and stains the extracellular matrix of the surface epithelium. The nuclei do not absorb the contrast and appear dark. This difference in contrast allows architectural analysis of the surface mucosa and aids in differentiating normal mucosa from neoplastic tissue. Currently there are 2 devices which allow CLE of the surface mucosa. The first device integrates the confocal laser microscope in the distal tip of the upper endoscope or the colonoscope. This system was developed by Pentax (Tokyo, Japan) and allows simultaneous endoscopic imaging; in addition, it frees the endoscopic working channel for other accessory devices. The second system is a probe-based CLE (pCLE; Cellvizio, Mauna Kea Technologies, Paris, France). The probe catheter can be used through the working channel of the conventional endoscope including the side viewing endoscope for examination of the common bile duct during endoscopic retrograde cholangiopancreatography. Since the introduction of CLE to the gastroenterology field, researchers have been exploring the clinical applications of this technique in various luminal disorders. Differentiating between hyperplastic, adenomatous, and neoplastic colonic tissue was one of the initial applications of the technique. Other emerging applications include screening for neoplasia in Barrett esophagus, early gastric cancer, and ulcerative colitis surveillance. In this issue of the J Clin Gastroenterol, 2 exciting new applications of CLE were reported by Liu et al and Loeser et al. Liu et al compared the epithelial gap density in the terminal ileum of patients with Crohn’s disease (CD) to normal controls, while Loeser et al reported their finding of pCLE examination of the common bile ducts in patients with indeterminate biliary stricture. In addition, both the groups replicated their CLE experience in animal models. Identification of the epithelial gaps in the intestinal mucosa using CLE examination is possible. Although epithelial gaps and goblet cells have the same appearance of dark hypodense rounded structures, Kiesslich et al provided feasible criteria to differentiate between the 2 structures. The lack of nuclei in epithelial gaps and the target lesion appearance of the goblet cells can easily differentiate between the 2 structures. Liu et al used the same criteria to quantify the number of epithelial gaps using pCLE in patients with CD and control patients who were referred to colonoscopy for other indications. In addition, the authors used a rigid confocal endomicroscopy to quantify the epithelial gaps in an animal model of Inflammatory Bowel Disease (IBD) (IL-10 deficient mice) compared with control. Indeed, the number of epithelial gaps was higher in IBD patients and in the IL-10 deficient mice compared with the control. This is consistent with the new literature emphasizing the role of intestinal barrier in IBD pathogenesis. The ability to confirm the diagnosis of IBD by quantifying the number of epithelial gaps sounds intriguing. However, there is a long way to go before incorporating this new application of CLE in clinical practice. The authors examined the epithelial gaps in normal mucosa of the Terminal Ileum (TI) in 8 CD patients and 6 controls. Because of the low number of patients, the authors could not draw a conclusion on whether patients with active disease (2 patients) had a higher number of epithelial gaps compared with patients with controlled disease. Also, it is not clear whether the degree of inflammation correlates with the number of the epithelial gaps. Intestinal permeability can be affected in various gastrointestinal disorders. How specific the increase in epithelial gaps is in diagnosing IBD is another question. What about epithelial gap numbers in infectious diarrhea or microscopic colitis? The answers to the above mentioned questions remain to be unfolded.

A prospective study of the risk of bacteremia in directed cholangioscopic examination of the common bile duct.

BACKGROUND AND AIMS The frequency of bacteremia during ERCP with cholangioscopy has not been well studied. There are no formal guidelines regarding antibiotic prophylaxis before ERCP with cholangioscopy. The aim was to estimate the frequency of bacteremia and subsequent infectious adverse events after ERCP with cholangioscopy. METHODS This prospective nonrandomized study performed in a single tertiary referral center included adult patients who were undergoing ERCP with cholangioscopic examination of the common bile duct. Blood cultures were drawn from patients before the procedure and 5 and 30 minutes after the procedure. Antibiotics were not given before or after the procedure. Patients were followed up after 24 hours and 1 week after the procedure for infectious adverse events. The primary outcome was bacteremia rate, and secondary outcomes were cholangitis rate and adverse events. RESULTS Fifty-seven patients were enrolled in the study with 60 procedures performed. The first procedure from each patient was considered in the analysis, and thus we included 57 patients with 57 procedures in this study analysis. Postprocedure bacteremia was seen in 5 of 57 procedures (8.8%; 95% confidence interval, 2.9%-19.3%). Four patients were readmitted with cholangitis (7.0%). Bacteremia was more common in patients who had cholangioscopy with biopsy sampling compared with patients who had cholangioscopy without biopsy sampling (P = .011). Cholangitis was significantly more common in patients with bacteremia than in those patients with a negative blood culture (P = .035). CONCLUSION ERCP with cholangioscopy is associated with a bacteremia rate of 8.8% and a cholangitis rate of 7.0%. Preprocedural antibiotics may be considered before cholangioscopy, especially if tissue acquisition with biopsy sampling is expected. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01673269.).

Estimation of the Adenoma Detection Rate From the Polyp Detection Rate by Using a Conversion Factor in a Predominantly Hispanic Population.

Background: Calculating the adenoma detection rate (ADR) is a complex process in contrast to the polyp detection rate (PDR) that can be easily calculated. The average adenoma to polyp detection rate quotient (APDRQ) was proposed as a conversion factor to estimate the ADR for individual endoscopists from the endoscopist’s PDR. However, this conversion factor was not validated in different practice settings. Goal: To validate the use of the proposed conversion factor in a practice setting with a predominantly Hispanic population. Study: We conducted a retrospective, cross-sectional study (December 2007 to November 2012) of screening colonoscopies at a university practice setting with an 86.9% Hispanic population. The actual ADR and PDR were calculated for all endoscopists. The weighted average of ADR to PDR ratio for each endoscopist was used to obtain APDRQ. The APDRQ was used as a conversion multiplier to estimate each endoscopist’s ADR using the single endoscopist’s PDR. Results: A total of 2148 screening colonoscopies were included. The average PDR for the whole group was 36.9% (range, 11% to 49%). The actual ADR was estimated as 25.5% (range, 11% to 37%). The average APDRQ for our group was 0.68. The estimated ADR was 25.48% (range, 8% to 33%). There was a high correlation between actual ADR and the estimated ADR (Pearson correlation=0.92). Conclusions: In a practice setting with a predominantly Hispanic population, a conversion factor can be used to estimate ADR from PDR providing a high degree of correlation with the actual ADR.