Relationship of reproductive hormones and neuromuscular disease of the gastrointestinal tract.
Mathias JR. Clench MH.
Department of Internal Medicine, University of Texas Medical Branch, Galveston, USA.
Functional disorders of the gastrointestinal tract comprise a common but ill-defined group of diseases; they primarily afflict women. Although predominantly involving nerve and muscle, the cellular and molecular bases of the pathogenesis of these functional disorders are unknown. Clinical studies indicate that some result from neural dysfunction within the enteric nervous system, others may be due to muscular problems, and the causes of still others remain unknown. Laboratory studies have shown that ovarian products such as progesterone, luteinizing hormone, human chorionic gonadotropin, and relaxin (but not estrogen), are neural antagonists of gastrointestinal motility. The production and secretion of these ovarian substances are controlled by gonadotropin-releasing hormone (GnRH) released from the hypothalamus; they probably act on gamma-aminobutyric acid receptors and alter chloride influx into the cell. GnRH analogs are effective drugs that downmodulate the hypothalamic-pituitary-gonadal axis and inhibit the secretion of gonadal products involved in such hormone-dependent diseases as endometriosis and prostate cancer. Acting on the GnRH receptors (seven transmembrane domain receptors) on myenteric neurons, GnRH analogs are also effective neural modulators in such disorders as functional bowel disease. These analogs are a promising new group of compounds that may be used to treat difficult gastrointestinal problems.
Use of botulinum toxin in the treatment of achalasia.
Schiano TD. Parkman HP. Miller LS. Dabezies MA. Cohen S. Fisher RS.
Department of Medicine, Temple University Hospital, Philadelphia, Pa.
Achalasia is a chronic esophageal motor disorder characterized by failure of the lower esophageal sphincter (LES) to relax during swallowing, aperistalsis of the esophageal body, and, often, an elevated resting LES pressure. Pneumatic dilation and Heller cardiomyotomy have been the time-honored, accepted treatments, but each may carry significant morbidity. Recently, intrasphincteric injection of botulinum toxin has been shown to be an effective treatment for achalasia, probably by reducing the excitatory cholinergic tone of the LES. Subjective and objective improvement have been reported in many patients with few reported adverse reactions. Clinical improvement generally lasts 2-6 months with patients often requiring repeat treatment. Although studies directly comparing botulinum toxin injection with pneumatic dilation and surgical myotomy are needed, botulinum toxin injection has rapidly become another therapeutic option in the treatment of achalasia.
Gene therapy for liver disease.
Davern TJ 2nd. Scharschmidt BF.
Department of Medicine, University of California, San Francisco 94143-0538, USA.
With major advances in biomedical science over the last 2 decades, the possibility of treating human disease at a genetic level has become a tantalizing possibility. As a result, a growing number of investigators are focusing on the development of techniques to deliver therapeutic genes into cells. The liver has been a model organ in the development of this gene transfer technology. This review focuses on the attributes and limitations of the current gene delivery systems that have been explored in the context of liver disease and highlights the obstacles that must be addressed before hepatic gene therapy becomes a clinical reality.
A prokinetic approach to treatment of gastroesophageal reflux disease.
Achem SR. Robinson M.
Division of Gastroenterology & Nutrition, Mayo Clinic, Jacksonville, Fla.
Currently available medications for gastroesophageal reflux disease (GERD) vary in mechanisms of action from neutralization or suppression of gastric acid to improving underlying upper gastrointestinal dysmotility. This article reviews the clinical efficacy of pharmacological agents used to treat GERD and provides a rationale for considering a primary prokinetic approach to antireflux treatment which will be applicable to many patients. Treatment trials in acute GERD have demonstrated unexpectedly prolonged maintenance of high esophageal pH with tablet and liquid antacid formulations. However, there are no well-designed placebo-controlled trials of antacids for esophageal mucosal healing. H2 receptor antagonists (H2RAs) at conventional doses relieve reflux symptoms in at least 50% of reported series of GERD patients, and they can also provide endoscopic healing in 27-45% of the cases. Therapy with more potent acid-suppressive agents such as proton pump inhibitors (PPIs) may lead to improved symptomatic relief and to superior healing compared with H2RA therapy, especially in those patients with more advanced erosive esophagitis. Promotility agents, particularly cisapride, offer symptom relief and healing rates which are quite similar to standard H2RA treatment. GERD tends to be a chronic and relapsing condition. Cisapride has been shown to be quite effective in maintaining remission in GERD patients, including endoscopic remission in the lesser degrees of esophagitis. This may be accomplished with relatively low and cost-effective dosing in many individuals. For the small proportion of patients who manifest severe grades of esophagitis, PPI therapy is associated with lower relapse rates than either H2RA or prokinetic treatment. Overall, a strong case can be made for the empirical selection of promotility therapy for the large numbers of GERD patients who do not have documented severe erosive disease.
Antimicrobial treatment of intra-abdominal infections.
Elsakr R. Johnson DA. Younes Z. Oldfield EC 3rd.
Department of Internal Medicine, Eastern Virginia Medical School, Norfolk 23502, USA.
There have been several recent changes that influence the management of intra-abdominal infections. These changes include important developments in antibiotic resistance such as increases in pneumococcal resistance, emergence of multi-drug-resistant enterococcal isolates, and decreasing sensitivity of anaerobes and gram-negative rods. In addition there are new antibiotics such as piperacillin/tazobactam, and new antibiotic dosing regimens such as single daily dosing of aminoglycosides. In this article, we will review the therapeutic approach to intra-abdominal infections with special emphasis on the various forms of peritonitis, cholecystitis, cholangitis, and diverticulitis. Several new concepts about the treatment of enterococcus, the management of bacterial and fungal peritonitis, and the prevention of spontaneous bacterial peritonitis will also be reviewed. Specific recommendations for the management of the different infections including antibiotic doses and costs will be provided. Finally the role of invasive procedures in the management of some of the infections will be explored.
Recent developments in the molecular characterization of Barretts esophagus.
Fitzgerald RC. Triadafilopoulos G.
Gastroenterology Section, Veterans Affairs Health Care System, Palo Alto, Calif., USA.
Barrett's esophagus, or specialized intestinal metaplasia, is a common condition associated with gastroesophageal reflux and an increased risk for adenocarcinoma of the esophagus and gastric cardia. Currently, clinical surveillance for early detection of adenocarcinoma relies on the histopathological assessment of dysplasia. In this review we present data from the published literature, and combine this with results from our own research, to address what is currently known about the environmental factors and the molecular changes thought to be important in the pathogenesis of Barrett's esophagus. The most important and well-characterized molecular changes, preceding the development of dysplasia, are alterations in the p53 and erbB-2 genes and aneuploidy. These molecular changes, as well as environmental influences, such as the quality and quantity of gastroduodenal refluxate, may result in abnormal cell proliferation which in turn promotes further genetic abnormalities and deregulation of cell growth. The identification of molecular changes, in the context of predisposing environmental factors, will enhance our understanding of the malignant progression of Barrett's esophagus leading to more effective surveillance and treatment.
Investigative techniques in the assessment of oral-pharyngeal dysphagia.
University of New South Wales and Department of Gastroenterology, St. George Hospital, Sydney, Australia.
Oral-pharyngeal dysphagia is a common problem with a high morbidity and mortality. In general, it is not managed as well as esophageal dysphagia by gastroenterologists. A number of techniques are now available for the assessment of oral-pharyngeal dysphagia. However, a careful clinical assessment followed by a video barium swallow is all that is required for the diagnosis and management in the majority of patients. Pharyngeal manometry is likely to play an increasingly important role in the assessment of difficult or atypical cases in whom it can provide functional information not achievable with videoradiography alone. Videolaryngoscopy is a quick and simple way of detecting structural lesions and of assessing deglutitive airway protection. Videolaryngoscopy is non-invasive and easily performed in an office setting. Ultrasonography is a convenient way of assessing lingual function, but provides no more information than the video barium swallow. Pharyngeal scintigraphy is likely to assume a greater clinical relevance as a means of quantifying swallow efficiency and response to therapy.
Endoscopic therapy of chronic and recurrent pancreatitis.
Waxman I. Freedman SD. Zeroogian JM.
Pancreaticobiliary Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass, USA.
Endoscopic pancreatic therapy is emerging as an exciting nonoperative alternative in the management of chronic pancreatitis, in particular in cases where pancreatic duct obstruction due to stones, protein plugs, or strictures is present. Although the preliminary results available are promising, prospective randomized trials comparing endoscopic and surgical techniques are much needed. Furthermore, the published data come from large endoscopic centers with very high levels of technical skill and experience, and, therefore, its wide-spread clinical use is limited. Time and well-designed prospective randomized clinical trials comparing surgical versus endoscopic techniques will help define the role of these procedures in the treatment of chronic pancreatitis.
Department of Gastroenterology, Cleveland Clinic Foundation, Ohio 44195, USA.
Zenker's diverticulum is a pouch protruding posteriorly above the upper esophageal sphincter, in the Killian's triangle, an area of relative weakness. Zenker's diverticulum was thought, for many years, to occur as a result of cricopharyngeal incoordination but more recent evidence points to poor upper sphincter compliance with diminished sphincter opening and increased hypopharyngeal pressures. Small Zenker's diverticula may be asymptomatic. As they become larger, symptoms include dysphagia, food regurgitation, and a sensation of globus. The best diagnostic method is a barium swallow with attention to the cricopharyngeal area. Although gastroesophageal reflux may be responsible for many throat symptoms, the relationship of reflux to the pathogenesis of Zenker's diverticulum is speculative. The treatment of Zenker's diverticulum is surgical. There have been many variations in technique over the years. Diverticulectomy with cricopharyngeal myotomy remains the most frequently performed operation. Endoscopic treatment with or without laser stapling has been reported but is not popular in the United States.
Oxidative stress and antioxidants in intestinal disease.
Thomson A. Hemphill D. Jeejeebhoy KN.
St. Michael's Hospital, University of Toronto, Ont, Canada.
Oxidative injury caused by free radicals is an important cause of tissue injury now recognized to occur in inflammation, ischemia and by the action of xenobiotics. It is also recognized to induce gene mutation and promote carcinogenesis. In this review the general concept of nett free radical injury counterbalanced by antioxidants is discussed as oxidative stress. The role of oxidative stress in intestinal ischemia, radiation enteritis, inflammatory bowel disease and the promotion of gastric and colorectal cancer is discussed. The data for the role of oxidative stress in the pathogenesis of ischemic, inflammatory and radiation induced disease are strong, but interventional studies with antioxidants have shown only weak beneficial effects in the above diseases. Therefore the role of antioxidants in the therapy of gastrointestinal diseases remains controversial and should be the subject of controlled trials.
Gastric stump cancer: what is the risk?
Safatle-Ribeiro AV. Ribeiro U Jr. Reynolds JC.
University of Pittsburgh Medical Center, PA, USA.
Patients who have undergone partial gastric resections are at an increased risk for the development of cancer in the gastric remnant. The overall risk increases over time and is higher in patients with an initial diagnosis of gastric rather than duodenal ulcer, in men and following partial gastrectomy with Billroth II reconstruction. The site of tumor growth is predominantly in the anastomotic area, but may occur anywhere in the stump. Enterogastric reflux, achlorhydria, bacteria overgrowth, and Helicobacter pylori appear to be the major factors involved in the etiopathogenesis of the gastric stump cancer. Surveillance of these patients with endoscopy and multiple biopsies may provide the means to diagnose tumors at an early stage, but the cost-benefit ratio of surveillance requires further study. Despite the magnitude of alterations in gastric stump mucosa, unfortunately, at this time we do not have good predictors of patients who will develop a cancer.
Gastrointestinal and hepatic manifestations of hereditary hemorrhagic telangiectasia.
Sharma VK. Howden CW.
Department of Internal Medicine, University of South Carolina School of Medicine, Columbia, USA.
Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber (ORW) disease is an autosomal-dominant disorder that frequently presents with gastrointestinal bleeding which may be a diagnostic and therapeutic challenge. Hepatic involvement in this disease is increasingly recognized and poses another therapeutic challenge. With advances in genetic screening and diagnostic procedures, and the increasing awareness of the condition by physicians and patients, this disease is being diagnosed more often. This article reviews the available literature on gastrointestinal and hepatic manifestations of HHT, and the various diagnostic and therapeutic modalities available for its management.
Overview of imaging in colorectal cancer.
Ott DJ. Wolfman NT. Scharling ES. Zagoria RJ.
Department of Radiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1088, USA.
Accurate staging of colorectal carcinoma (CRC) at initial diagnosis is critical for proper management of this disease. Computed tomography (CT) is often used for preoperative staging and is complementary to the clinical assessment of the patient and to the use of other imaging techniques, such as endoluminal ultrasound (US). CT can identify those patients who may benefit from local radiation therapy, hepatic resection or cryoablation, or intra-arterial chemotherapy. Endoluminal US may detect patients with early disease and alter their course of therapy, especially in those with rectal carcinoma in which limited surgery might be performed. CT is generally the modality of choice for imaging the postoperative patient. CT clearly depicts the operative area, particularly after abdominoperitoneal resection, and can be used to guide percutaneous biopsy of masses. The role of magnetic resonance imaging in CRC remains to be defined. In this review, we discuss the current roles of these various imaging modalities in the management of this disease.
Diagnosis and management of appendiceal mucoceles.
Soweid AM. Clarkston WK. Andrus CH. Janney CG.
Department of Internal Medicine, St. Louis University Health Sciences Center, MO, USA.
Preoperative diagnosis of appendiceal mucoceles is rare. If untreated, one type of mucoceles may rupture producing a potentially fatal entity known as pseudomyxoma peritonei. The importance of diagnosing appendiceal mucoceles is highlighted through a case presentation of a woman who had an incidental finding of mucinous cystadenoma of the appendix during colonoscopic evaluation for occult gastrointestinal bleeding. A detailed review of the medical literature regarding appendiceal mucoceles is presented, with emphasis on the pathologic, clinical, radiologic, and evolving endoscopic features. Surgical options and prognosis are discussed.
Ulcerative colitis and colon cancer: more controversy than clarity.
Snapper SB. Syngal S. Friedman LS.
Gastrointestinal Unit, Massachusetts General Hospital, Boston 02114, USA.
Although it is generally accepted that the risk of colorectal cancer in patients with ulcerative colitis is increased compared with the general population, the management of this increased risk remains controversial. Patients with pancolitis of > 8 years duration should consider periodic colonoscopic surveillance or prophylactic colectomy. For patients unwilling to undergo prophylactic colectomy, colonoscopic surveillance annually or biennially is recommended. High-grade dysplasia or low-grade dysplasia in association with a lesion or mass is an indication for colectomy when confirmed by 2 pathologists. Repeat colonoscopic surveillance (in 3-6 months) or colectomy is recommended for confirmed low-grade dysplasia.
Management of bile duct stones in the era of laparoscopic cholecystectomy.
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7878, USA.
The development of laparoscopic cholecystectomy has transformed many aspects of gallstone disease management, particularly the care of patients with known or suspected bile duct stones. New obstacles to operative access to the bile duct have stressed the importance of accurate clinical prediction and detection of bile duct stones and led to increased reliance on nonsurgical approaches, especially pre- or postoperative endoscopic retrograde cholangiopancreatography and sphincterotomy, as well as spurring the development of new techniques such as laparoscopic common bile duct exploration. This work reviews the key features and rational usage of the endoscopic, laparoscopic and open surgical procedures, as well as other adjunct techniques, employed in the treatment of bile duct stones, emphasizing current options in the approach to this problem in the perilaparoscopic cholecystectomy setting. Management of bile duct stones in other special clinical circumstances and the potential future role of emerging technologies are also discussed.
Upper respiratory tract complications of gastroesophageal reflux in adult and pediatric-age patients.
Wyeth Nutritionals International, Philadelphia, PA 19101, USA.
Upper airway complications of gastroesophageal reflux occur much less frequently than those abroad to the upper esophageal sphincter; however, laryngitis, laryngeal and/or tracheal stenosis, globus syndrome, oropharyngeal dysphagia, otitis media, sinusitis, and rhinitis can all be associated with significant morbidity and occasional mortality in both adult and pediatric patients. Sudden infant death and apparent life-threatening events, both found only in pediatric patients, are even less frequently associated with gastroesophageal reflux. Today, excellent diagnostic methods are available, such as proximal 24-hour pH probe evaluations or scintigraphy, making proper diagnosis much easier than previously. Although today's medical and surgical methods do not affect the underlying pathophysiology, they are frequently very effective in controlling signs and symptoms, allowing the patients to return to resume their normal life-styles and livelihoods.
Bile acid diarrhea.
University of Rochester, School of Medicine and Dentistry, N.Y., USA.
Bile acids normally undergo enterohepatic circulation. When this circulation is interrupted, bile acids enter the colon in increased concentrations. Here, they produce Cl- secretion by a calcium- and cyclic AMP-dependent mechanism, resulting in diarrhea. Cholestasis may lead to serum bile acid concentrations high enough to produce colonic secretion by serosal surface effects. When resection or disease interferes with ileal function, the resulting diarrhea can be clearly attributed to bile acid malabsorption. In other states, such as postcholecystectomy diarrhea and idiopathic bile acid diarrhea, the role of bile acids is less well defined. 23-75Selena-25-homotaurocholic acid provides a way of tracing the metabolism of bile acids and their enterohepatic circulation in vivo. Metabolized similarly to natural bile acids, its circulation is easily traced by scintigraphy. Barium x-rays, serum concentrations of bile acids or bile acid intermediates, and tests of vitamin B12 absorption provide indirect measures of ileal function. Careful history and examination combined with one of many the available tests of ileal function allow a diagnosis. A therapeutic trial with a bile acid binding resin confirms the impression and treats the diarrhea.