Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

BACKGROUND AND STUDY AIMS: The AIM-II Trial included patients with nondysplastic Barrett's esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. PATIENTS AND METHODS: Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barrett's esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. RESULTS: Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). CONCLUSIONS: In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

Efficacy of neodymium:YAG laser therapy for gastric antral vascular ectasia (GAVE) following hematopoietic cell transplant.

We determined the incidence of severe bleeding from gastric antral vascular ectasia (GAVE) after myeloablative hematopoietic cell transplant and the outcomes after treatment with endoscopic neodymium:YAG laser photocoagulation. From 1992 to 2005, the incidence of severe bleeding from GAVE was 6/4491 (0.13%). All patients had received oral busulfan and four had sinusoidal obstruction syndrome. Gastrointestinal bleeding began a median of 53 days after transplant (range 15-2952). After GAVE was diagnosed by endoscopic and histologic findings, a median of three (range 2-7) sessions of laser therapy were required to control the bleeding with a median of 2737 J (range 1117-6160 J) per session. A median of 16 units (range 4-44) had been transfused prior to laser therapy and a median of four additional units (range 0-113) were transfused until bleeding was controlled. All patients were followed for at least 70 days after the last laser therapy session, with no further episodes of bleeding. Complications were mild and included abdominal pain and asymptomatic ulceration; however, one patient required gastrectomy due to gastric necrosis following transarterial embolizations. In summary, severe bleeding from GAVE is rare following hematopoietic cell transplant. Treatment with endoscopic therapy using the Nd:YAG laser is safe and effective.

Systematic review: acute colonic pseudo-obstruction.

Acute colonic pseudo-obstruction is the clinical syndrome of acute large bowel dilatation without mechanical obstruction that is an important cause of morbidity and mortality. Acute colonic pseudo-obstruction occurs in hospitalized or institutionalized patients with serious underlying medical and surgical conditions. The pathogenesis of acute colonic pseudo-obstruction is not completely understood but likely results from an imbalance in the autonomic regulation of colonic motor function. Metabolic or pharmacological factors, as well as spinal or retroperitoneal trauma, may alter the autonomic regulation of colonic function, leading to excessive parasympathetic suppression or sympathetic stimulation. This imbalance results in colonic atony and dilatation. Early recognition and appropriate management are critical to minimizing morbidity and mortality. The mortality rate is estimated at 40% when ischaemia or perforation occurs. The best-studied treatment of acute colonic pseudo-obstruction is intravenous neostigmine, which leads to prompt colon decompression in the majority of patients after a single infusion. In patients failing or having contraindications to neostigmine, colonoscopic decompression is the active intervention of choice. Surgery is reserved for those with peritonitis or perforation.

Biliary complications after liver transplantation: the role of endoscopy.

Biliary complications are important causes of early and late postoperative morbidity and mortality after liver transplantation and are seen in 10-20 % of the patients. The common biliary complications include bile leaks, stones or debris, and anastomotic strictures. Less common complications are hilar strictures, intrahepatic strictures, and papillary stenosis/dysfunction. The complications are similar in living-donor and cadaveric liver transplantations, except for a higher incidence of bile leaks among living-donor transplant recipients. The clinical presentation of post-liver transplant bile duct complications is often subtle, and noninvasive imaging studies may sometimes fail to detect mild but clinically significant stenoses or small leaks. Early recognition and prompt treatment of biliary complications following liver transplantation reduces the morbidity and improves long-term graft and patient survival. In this report, we discuss the role of endoscopy in the diagnosis, treatment options, and the outcome for patients with biliary complications following liver transplantation.

Review article: appropriate use of proton pump inhibitors with traditional nonsteroidal anti-inflammatory drugs and COX-2 selective inhibitors.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used classes of medications in the USA, annually accounting for over 100 million prescriptions. Gastrointestinal complications associated with NSAIDs are common, and result in a substantial amount of morbidity and mortality, despite the advent of the cyclooxygenase-2 selective inhibitors or 'coxibs'. Emerging clinical and economic data suggest that, depending on the baseline risk to patients, the use of a traditional NSAID alone or in combination with a proton pump inhibitor are effective and well tolerated alternatives to coxibs. The optimal therapeutic strategy for NSAID selection and use of co-therapy should be guided by a consideration of each patient's risk of having an adverse event arising from the NSAID. Patients at the highest risk for gastrointestinal complications with traditional NSAIDs are those with a history of an ulcer or ulcer complication, those of advanced age (greater than 65 years), and those receiving concurrent aspirin, anticoagulants or corticosteroid therapy. Proton pump inhibitor co-therapy is highly effective in reducing NSAID-related dyspeptic symptoms, healing the injured mucosa even in those who continue to ingest NSAIDs, and preventing gastrointestinal complications. In addition to their selective use in patients who experience NSAID-related dyspepsia and other symptoms, proton pump inhibitor co-therapy should be considered in those at high risk (with coxib or traditional NSAID therapy) and is necessary in high-risk patients receiving aspirin, with or without NSAID therapy.

Development of a fast scanning miniature probe and methods of dispersion management for high-resolution optical coherence tomography.

We present a design of a miniature fiber-optic probe capable of rapid lateral scanning. The miniature probe permits forward-looking optical coherence tomography (OCT) imaging of internal organs in real time. Fast lateral scanning also enables a new real-time image acquisition sequence, potentially permitting real-time focus tracking. To perform sensitive heterodyne detection, a sufficient Doppler frequency is achieved by using an electro-optic (EO) phase modulator. In this paper we describe an effective approach to compensate the dispersion induced by the EO crystal up to the third order. We show that an optimal axial resolution offered by the light source can be recovered through the dispersion management. Preliminary results of real-time OCT imaging of biological tissues with the lateral-priority scanning probe are presented.

Familial fibrocystic pancreatic atrophy with endocrine cell hyperplasia and pancreatic carcinoma.

Understanding the pathology of familial pancreatic carcinoma may provide important insights into pancreatic tumorigenesis. We now describe in detail the pancreatic pathology of an autosomal dominant pancreatic carcinoma kindred with distinct clinical, genetic, and pathologic manifestations differing from all other reported forms of sporadic or familial pancreatic neoplasia. Affected individuals develop a prodrome of diabetes mellitus, pancreatic exocrine insufficiency, and characteristic pancreatic imaging abnormalities. Eleven family members have undergone total pancreatectomy, revealing a unique and characteristic fibrocystic, lobulocentric pancreatic atrophy. This was patchy to diffuse in distribution and was invariably associated with a nesidioblastosis-like endocrine cell hyperplasia. All but one resected pancreas demonstrated glandular epithelial dysplasia: 10 had low-grade dysplasia (pancreatic intraductal neoplasia grade II of III or PanIN II) and seven also had high-grade dysplasia (pancreatic intraductal neoplasia grade III of III or PanIN III). Dysplasia was multifocal in small-to medium-sized duct-like structures within areas of acinar atrophy, microcystic change, and mucinous hyperplasia. Two pancreata had carcinomas of multiple and unusual histologic subtypes, including small cell undifferentiated carcinoma and giant cell anaplastic carcinoma. The findings in this kindred yield important information on a distinctive and previously unrecognized pancreatic cancer precursor. Recognition of this entity may help identify additional kindreds and perhaps the underlying genetic defect. As is the case for other familial cancers, the as yet unknown specific genetic defect may have wider implications for pancreatic cancer in general.

Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis.

BACKGROUND: Patients with ulcerative colitis and primary sclerosing cholangitis are at high risk for colonic dysplasia and cancer. This risk approaches 50% after 25 years of colitis. Ursodiol has been shown to protect against development of colorectal neoplasia in animal models. OBJECTIVE: To assess the relationship between ursodiol use and colonic dysplasia, the precursor to colon cancer, in patients with ulcerative colitis and primary sclerosing cholangitis. DESIGN: Cross-sectional study. SETTING: University medical center. PATIENTS: 59 patients with ulcerative colitis and primary sclerosing cholangitis who were undergoing colonoscopic surveillance for colonic dysplasia. MEASUREMENTS: Use of ursodiol was assessed in all patients. The presence or absence of colonic dysplasia was evaluated by colonoscopic surveillance. Other variables assessed were age at onset and duration of ulcerative colitis; duration of primary sclerosing cholangitis; Child-Pugh classification; and use of sulfasalazine, other 5-aminosalicylic acid preparations, prednisone, cyclosporine, azathioprine, and methotrexate. RESULTS: Ursodiol use was strongly associated with decreased prevalence of colonic dysplasia (odds ratio, 0.18 [95% CI, 0.05 to 0.61]; P = 0.005). The association between dysplasia and ursodiol use remained after adjustment for sex, age at onset of colitis, duration of colitis, duration of sclerosing cholangitis, severity of liver disease, and sulfasalazine use (adjusted odds ratio, 0.14 [CI, 0.03 to 0.64]; P = 0.01). Younger age at onset of colitis was associated with an increased risk for dysplasia. CONCLUSIONS: Ursodiol use appears to be associated with a lower frequency of colonic dysplasia in patients with ulcerative colitis and primary sclerosing cholangitis. A randomized trial investigating the chemoprotective effect of ursodiol in patients with ulcerative colitis may be warranted.

Chronic atrophic gastritis and Helicobacter pylori infection among Japanese Americans in Seattle.

Gastric cancer is still a major cause of mortality due to cancer worldwide. The most common type of gastric cancer is intestinal type carcinoma, which usually occurs in stomachs containing chronic atrophic gastritis. Individuals with chronic atrophic gastritis are considered to be at increased risk for developing intestinal type carcinoma of the stomach. To examine the association between chronic atrophic gastritis and other gastric cancer risk factors, a cross-sectional study was conducted using serum samples and questionnaire information collected from 776 persons of full Japanese ancestry in the greater Seattle area in 1994. The presence of chronic atrophic gastritis and Helicobacter pylori infection was determined by measurement of serum pepsinogen levels and H. pylori antibodies, respectively. Based on multiple logistic regression, the significant predictors of chronic atrophic gastritis were age over 50 years, H. pylori infection, and 20 years or more lived in Japan. Alcohol consumption, smoking, prior peptic ulcer, and history of gastric cancer in parents were not significantly associated with chronic atrophic gastritis. The results imply that H. pylori infection since earlier life and other unknown exposure factors in Japan might have played an important role in the development of chronic atrophic gastritis.

Review article: nonsteroidal anti-inflammatory drug-associated gastrointestinal complications--guidelines for prevention and treatment.

Chronic ingestion of NSAIDs increases the risk for gastrointestinal complications, which range from dyspepsia to gastrointestinal bleeding, obstruction, and perforation. Among patients using NSAIDs, 0.1 to 2.0% per year suffer serious gastrointestinal complications. Patients who require analgesic therapy should be carefully assessed for the lowest possible dosage and shortest duration of NSAID use and for the potential of treatment with a non-NSAID pain reliever. These patients should also be assessed for factors that increase their risk of gastrointestinal complications, including increased age, concomitant anticoagulant or corticosteroid use, and past history of NSAID-associated gastrointestinal complications. The exact association between Helicobacter pylori infection and NSAID-related ulcer disease is unclear, and the routine testing and treatment of all NSAID using patients for H. pylori infection is not recommended at this time. NSAID-using patients who suffer from dyspepsia should have NSAIDs discontinued, the dosage changed, or be changed to a different class of NSAID. If NSAIDs cannot be discontinued, then an antisecretory agent should be initiated. Misoprostol prevents NSAID-associated gastrointestinal complications. Proton pump inhibitors are the most effective at healing NSAID-associated ulcers among patients who cannot discontinue NSAID therapy.

Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer.

BACKGROUND: Pancreatic cancer, the fourth most common cause of cancer death in the United States, is hereditary in an estimated 10% of cases. Surveillance of patients with a familial predisposition for pancreatic cancer has not been systematically evaluated. OBJECTIVE: To develop a surveillance program that can identify and treat patients who have precancerous conditions of the pancreas and a family history of pancreatic cancer. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENTS: 14 patients from three kindreds with a history of pancreatic cancer. INTERVENTIONS: Endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), spiral computed tomography, and serum carcinoembryonic antigen and CA19-9 analysis were performed in all patients. Four affected patients were tested for the K-ras mutation. MAIN OUTCOME MEASUREMENT: Pancreatic dysplasia was determined by histologic evaluation. RESULTS: Seven of the 14 patients were believed to have dysplasia on the basis of clinical history and abnormalities on endoscopic ultrasonography and ERCP and were referred for pancreatectomy. All 7 patients had histologic evidence of dysplasia in pancreatectomy specimens. Findings on endoscopic ultrasonography were subtle, nonspecific, and similar to those seen in patients with chronic pancreatitis. Findings on ERCP ranged from mild and focal side-branch duct irregularities and small sacculations to main-duct strictures and grapelike clusters of saccules. Some of these changes are typical of chronic pancreatitis, but others are more distinctive. Spiral computed tomography and serum tumor markers had low sensitivity in the detection of pancreatic dysplasia. Analysis for the K-ras mutation yielded positive results in 3 of 4 patients with dysplasia. CONCLUSIONS: Thorough screening of patients with a family history of pancreatic cancer is feasible. Clinical data combined with imaging studies (endoscopic ultrasonography and ERCP) can be used to identify high-risk patients who have dysplasia. The role of molecular genetic testing is uncertain at this time.

Neostigmine for the treatment of acute colonic pseudo-obstruction.

BACKGROUND: Acute colonic pseudo-obstruction -- that is, massive dilation of the colon without mechanical obstruction -- may develop after surgery or severe illness. Although it may resolve with conservative therapy, colonoscopic decompression is sometimes needed to prevent ischemia and perforation of the bowel. Uncontrolled studies have suggested that neostigmine, may be an effective treatment. METHODS: We studied 21 patients with acute colonic pseudo-obstruction. All had abdominal distention and radiographic evidence of colonic dilation, with a cecal diameter of at least 10 cm, and had had no response to at least 24 hours of conservative treatment. We randomly assigned 11 to receive 2.0 mg of neostigmine intravenously and 10 to receive intravenous saline. A physician who was unaware of the patients' treatment assignments recorded clinical response (defined as prompt evacuation of flatus or stool and a reduction in abdominal distention), abdominal circumference, and measurements of the colon on radiographs. Patients who had no response to the initial injection were eligible to receive open-label neostigmine three hours later. RESULTS: Ten of the 11 patients who received neostigmine had prompt colonic decompression, as compared with none of the 10 patients who received placebo (P<0.001). The median time to response was 4 minutes (range, 3 to 30). Seven patients in the placebo group and the one patient in the neostigmine group without an initial response received open-label neostigmine; all had colonic decompression. Two patients who had an initial response to neostigmine required colonoscopic decompression for recurrence of colonic distention; one eventually underwent subtotal colectomy. Side effects of neostigmine included abdominal pain, excess salivation, and vomiting. Symptomatic bradycardia developed in two patients and was treated with atropine. CONCLUSIONS: In patients with acute colonic pseudo-obstruction who have not had a response to conservative therapy, treatment with neostigmine rapidly decompresses the colon.

Biliary complications of orthotopic liver transplantation.

Biliary complications are a common cause of morbidity following orthotopic liver transplantation. Complications involving the biliary tree occur after 6-34% of all liver transplants performed, usually within the first 3 months after transplantation. Bile leaks and biliary strictures are the most common biliary complications, but sphincter of Oddi dysfunction, hemobilia, and biliary obstruction from stones, sludge, or casts have also been described. The risk of specific biliary complications is related to the type of biliary reconstruction performed at the time of transplantation. In this article, we review the major types of biliary reconstruction and their associated biliary complications. Specific risk factors for the development of biliary complications are outlined. Finally, the management of biliary complications is discussed, with an emphasis on the role of endoscopic therapy.

Role of endoscopy in nonsteroidal anti-inflammatory drug clinical trials.

Endoscopy is a useful tool that can be used to determine the acute or chronic gastrointestinal (GI) toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) and to confirm outcomes in clinical trials. However, since evaluations of endoscopic injuries are to some extent subjective (e.g., the endoscopic distinction between an erosion and an ulcer), such injuries must be clearly and correctly defined before the data can be analyzed and considered meaningful. Definitions of injury, endpoints, and protocol design must be consistent with the intent of the study. This becomes evident in drawing distinctions between acute injury, which may resolve, and chronic injury that occurs over a longer period of time. The intent of the study itself should be clearly defined and based on realistic and realizable goals. Only when these criteria are met, and preferably standardized, can clinically relevant studies be performed and compared.

Gastrointestinal side effects of nonsteroidal anti-inflammatory drugs.

The gastrointestinal (GI) tract is the most common location for side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs may cause problems in any part of the GI tract, from the esophagus to the rectum. The severity of these side effects ranges from nuisance symptoms such as dyspepsia to life-threatening ulcer complications. The diagnosis, treatment, and prevention of the various GI side effects of these commonly prescribed drugs are reviewed in this article.