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Motion--Laparoscopic Nissen fundoplication is more cost effective than oral PPI administration: arguments for the motion.

Gastroesophageal reflux disease is a mechanical disorder of the foregut. While medications can only provide symptom relief, surgery can correct the pathophysiological abnormality of the lower esophageal sphincter. The costs of medical and surgical therapy are much greater than the costs of medication or hospitalization alone. In the case of medical therapy, one must consider the costs of serial monitoring and of failed treatment. The effectiveness of treatment also depends on patient-related factors, including weight, socioeconomic factors, smoking, alcohol use, dietary habits and the use of nonsteroidal anti-inflammatory drugs. Surgical results depend on the experience and skill of the surgeon, as well as the attributes of the institution in which the procedure is undertaken. Therefore, studies that come from specialized centres may not be applicable to the community. Data from the author's facility indicate that laparoscopic Nissen fundoplication is the most cost effective option when it is undertaken by experienced surgeons on otherwise healthy patients who have documented gastroesophageal reflux disease.

Costs and Cost Analysis↗

Motion - All patients with GERD should be offered once in a lifetime endoscopy: arguments for the motion.

Proton pump inhibitor therapy is so successful at relieving reflux-related symptoms and healing esophageal erosions that it has supplanted formal diagnostic techniques, such as endoscopy and esophageal pH monitoring, for the initial management of gastroesophageal reflux disease. The response to antisecretory therapy is not indicative, however, of Barrett's esophagus or esophageal adenocarcinoma. Patients with prolonged and severe reflux symptoms, especially if they are over the age of 60 years, are at risk of these complications. For them, endoscopy is the only appropriate investigation for detecting Barrett's esophagus and dysplasia or cancer. Because of the difficulty in distinguishing dysplasia from inflammatory and regenerative changes, endoscopy should be undertaken while the patient is on effective antisecretory therapy. Endoscopy should be offered only to patients who are suitable for further therapy (especially esophagectomy), and only if they understand the implications of abnormal findings. The published evidence suggests that the application of clear guidelines would not overwhelm health care resources, and that fewer than 20% of patients with Barrett's esophagus would eventually undergo endoscopic surveillance.

Endoscopy, Digestive System↗

Motion - Screening and surveillance of Barrett's epithelium is practical and cost effective: arguments against the motion.

The issue of whether to screen individuals for Barrett's esophagus (BE) to prevent esophageal adenocarcinoma (EAC) is highly controversial. Important considerations are that BE is not highly prevalent in the general population and that not many patients with BE develop or die from EAC. Studies that suggest an improved prognosis from surveillance programs are susceptible to lead-time bias. Most of the principles for effective screening, as outlined by the World Health Organization, are not met by endoscopic screening and surveillance protocols. The diagnosis of BE (and dysplasia) is often unclear. Most patients with BE are not identified by screening, and few deaths would be prevented by surveillance. A decision analysis found that the most cost effective screening protocol would be every five years, but the costs associated with prolongation of life are very high, even if a group at high risk for EAC could be identified.

Barrett Esophagus↗

Motion - the available treatments for hepatitis C are cost effective: arguments against the motion.

Hepatitis C is a prevalent infection in North America. However, the natural history of hepatitis C virus (HCV) infection in the general population is not fully understood. Available cohort-based studies suggest that only a relative minority of patients develop significant liver disease, such as cirrhosis and/or hepatocellular carcinoma. Other studies, mostly conducted based on referral patients with established disease, portray much more serious consequences of HCV infection. Although a substantial improvement has been made in the treatment for HCV, the overall impact of antiviral therapy in altering the natural course of HCV infection remains uncertain. Therapeutic trials involve narrow selection criteria that would exclude the majority of hepatitis C patients in the community, and are conducted in ideal settings that may not be generalizable to the average practice setting. Demographic groups that are at high risk of developing severe liver disease include older male patients who consume alcohol. In contrast, antiviral therapy is more effective in young and female patients and those who do not drink alcohol. Thus, patients who appear to be successfully treated may not be those for whom clearance of the virus would be beneficial. Cost-effectiveness studies published to date have not been able to fully address the complex and heterogeneous matrix of the factors that influence the natural history of HCV infection and treatment response. In summary, there is a significant degree of uncertainty about many assumptions that are necessary in creating computer models to estimate the cost-effectiveness of HCV therapy. When interpreting the results of cost effectiveness analyses regarding the treatment of HCV infection, it is important to be aware of the underlying assumptions that are incorporated in the model and the data on which they are based. Given these limitations, vis- -vis the expense, toxicity and yet limited effectiveness of the currently available antiviral agents, one should not blindly accept a conclusion that treatment for hepatitis C is cost effective.

Age Factors↗

Motion - All patients with GERD should be offered once in a lifetime endoscopy: arguments against the motion.

The evidence for the recommendation that patients with gastroesophageal reflux disease (GERD) be offered once in a lifetime endoscopy is weak and is not supported by any clinical trials. GERD is a very prevalent condition, yet only 10% of patients with GERD have Barrett's esophagus (BE). Esophageal adenocarcinoma (EAC) is a rare condition and is uncommon even among patients with BE. A decision analysis found that surveillance of BE patients is performed because of inflated estimates of the rate of progression from BE to EAC. Dysplasia more often regresses to more benign histological findings than to cancer, and transient dysplasia can also lead to a high rate of unnecessary endoscopy. Even though practice guidelines about endoscopic surveillance have been published, there is no consensus among gastroenterologists about appropriate protocols, and many physicians are more aggressive than the guidelines. It has not been proved that surveillance saves lives, in part because BE rarely leads to death from EAC. The favourable results from some specialized centres may not be widely applicable. The recommendation for 'once in a lifetime' endoscopy for GERD patients is premature.

Endoscopy, Digestive System↗

Motion--Helicobacter pylori worsens GERD: arguments for the motion.

There are several reasons for eradicating Helicobacter pylori in patients with chronic gastroesophageal reflux disease (GERD). Perhaps the most compelling is the evidence that chronic acid suppression therapy can lead to the development of atrophic gastritis, a premalignant condition, in patients with H pylori infection. Epidemiological data that suggest that H pylori is less prevalent in GERD patients than in control subjects may be susceptible to publication bias, and confounding social and environmental factors may also be involved. Although it has been thought that eradication of the organism might lead to increased esophageal acid exposure, this has not been demonstrated in practice. Studies that appeared to show that GERD could be provoked by antimicrobial therapy of duodenal ulcers also have methodological weaknesses. Underlying GERD symptoms might be unmasked after withdrawal of acid-suppression therapy, for reasons that are unrelated to H pylori. In fact, eradication of the organism has been shown to decrease heartburn in patients with peptic ulcer disease. When H pylori is successfully eradicated in patients with GERD, relapse rates are not increased, and the disease-free interval seems to be prolonged. Eradication of the organism is a wise policy in patients who face long term acid-suppression therapy for GERD.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Motion - all patients with NASH need to have a liver biopsy: arguments against the motion.

Most cases of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are suspected on the basis of the exclusion of viral, autoimmune, metabolic and genetic causes of chronic liver disease in patients with chronic elevation of aminotransferase enzymes. However, the definitive diagnosis of NASH requires liver biopsy. Valuable blood tests include hepatitis B and C serology, iron profile, alpha 1-antitrypsin phenotype, ceruloplasmin, antinuclear antibody and antismooth muscle antibody, and serum protein electrophoresis. If these tests are negative or normal, and if there are no symptoms or signs of chronic liver disease, it is unlikely that a specifically treatable liver disease would be discovered at biopsy. The prevalence of NAFLD in the general population appears to be approximately 20%, and 2% to 3% of people have NASH. There is no proven specific therapy for the spectrum of nonalcoholic liver disease; therefore, the management of the patient with NASH is not likely to be changed after histological assessment. Bleeding, sometimes fatal, and other complications requiring hospitalization can occur, and liver biopsies should not be undertaken without clear clinical indications. The high cost of undertaking histological assessment of all persons with asymptomatic elevations of liver enzymes cannot be justified in view of the risks and limited clinical benefits.

Biopsy, Needle↗

Motion - all patients with NASH need to have a liver biopsy: arguments for the motion.

Previously regarded as an obscure disorder, nonalcoholic steatohepatitis (NASH) has recently emerged as an important chronic liver disease. NASH is within a spectrum of disorders characterized by excessive accumulation of fat in the liver, including simple hepatic steatosis (fatty liver), inflammation and necrosis (steatohepatitis), and fibrosis. Collectively, the disorders are called nonalcoholic fatty liver disease (NAFLD). Estimates of the prevalence of these individual conditions are suspect because liver biopsy is required for definitive diagnosis and is not generally performed. Although these conditions have traditionally been thought of as diseases of obese women, and are frequently associated with diabetes mellitus and hypertriglyceridemia, they have also been identified in lean men. Insulin resistance appears to be a common factor. These conditions are difficult to distinguish from each other clinically, and no biochemical or radiological test reliably establishes the diagnosis. A ratio of serum aspartate to alanine aminotransferase levels of less than one can distinguish NAFLD from alcoholic liver disease, but this is a nonspecific finding. Fatty infiltration imparts a diffuse echogenicity to the liver at ultrasonography, but this test cannot easily distinguish fat from fibrous tissue or identify cases of NASH. Only histological examination can establish the diagnosis of NASH, grade its severity, determine the prognosis and guide treatment.

Alanine Transaminase↗

Motion - prophylactic banding of esophageal varices is useful: arguments for the motion.

Variceal hemorrhage is a frequent complication of cirrhosis and is associated with a high mortality rate, especially in patients with decompensated liver disease. Endoscopy is useful in identifying factors that predict a high likelihood of bleeding, including large varices and red colour signs. Endoscopic rubber band ligation has superseded sclerotherapy in the prevention of both recurrent hemorrhage and the first episode of bleeding, because it causes fewer complications and requires fewer sessions to eradicate varices. It has been proven to be more effective than nontreatment in the primary prophylaxis against variceal hemorrhage. There is extensive literature that has found that band ligation is more effective than beta-adrenergic receptor antagonists at preventing the first variceal hemorrhage. There is ongoing debate about the relative merits of these two approaches, but the available evidence supports the conclusion that band ligation is the treatment of choice in the primary prevention of variceal bleeding. Trials of combined medical and endoscopic therapy are eagerly awaited, and the author suspects that it may prove to be more effective than either modality alone.

Adrenergic beta-Antagonists↗

Motion--Helicobacter pylori causes or worsens GERD: arguments against the motion.

Data from large epidemiological studies show that Helicobacter pylori is less prevalent in patients with gastroesophageal reflux disease (GERD) than in control subjects. The more virulent cagA-positive strains of the organism are also less commonly seen in patients with erosive esophagitis and in those with Barrett's esophagus than in those with less severe forms of GERD. Although the relationship between H pylori and gastric physiology is complex, the organism has little effect on acid secretion in most North American or Western European subjects, and has a net suppressive effect, especially in elderly subjects, in other parts of the world. Thus, the organism has a potential protective effect against GERD, which is exacerbated by gastric acidity. H pylori has no proven effect on other gastric factors that might provoke reflux, including delayed gastric emptying or inappropriate relaxation of the gastric fundus. Two well-designed interventional studies have found that eradication of H pylori either provoked GERD or had no effect. A third smaller study, which seemed to demonstrate that persistent infection was associated with GERD, was flawed, in that the two treatment groups were not comparable. The evidence thus does not support the idea that H pylori infection provokes or aggravates GERD.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Motion - patients with primary sclerosing cholangitis should undergo early liver transplantation: arguments against the motion.

Liver transplantation is an accepted form of treatment for patients with primary sclerosing cholangitis (PSC) and can provide long term survival. Cholangiocarcinoma occurs in 10% to 20% of patients with PSC, is difficult to diagnose and has a poor prognosis. It has been proposed that liver transplantation be undertaken early in the course of the PSC, before cancer develops. Such a proposal would have significant implications for the method of assigning priority to patients awaiting liver transplantation. Other patients on the waiting list would experience further delays, while there is no proven benefit for PSC patients. Few patients with this disease are removed from the waiting list because they developed cancer. If one were to state that PSC patients warrant special consideration because of the hypothetical risk of cholangiocarcinoma, the same argument could be applied to patients with hepatitis C and other causes of cirrhosis, who are at increased risk of hepatocellular carcinoma. The transplant allocation system is applied in an equitable fashion to patients with a large variety of liver diseases. Alteration of this system to benefit a small number of patients with PSC would violate the principles on which it was created, and cannot be justified.

Cholangiocarcinoma↗

Motion - patients with primary sclerosing cholangitis should undergo early liver transplantation: arguments for the motion.

Primary sclerosing cholangitis (PSC) is a condition of unknown etiology that causes progressive inflammation, fibrosis and obliteration of the intrahepatic and extrahepatic biliary tree. There is no medical cure, and ursodeoxycholic acid and other drugs have not been shown to affect the natural history of the disease. Endoscopic dilation is of value only in the relief of symptoms and complications related to dominant strictures. Cholangio- carcinoma occurs in a substantial minority of cases, especially those with ulcerative colitis and cirrhosis, and is often not clinically apparent before surgery. There are no good serologic tests for early cancers. Because this tumour has such a dismal prognosis, some authorities recommend that liver transplantation be undertaken before its development. This procedure is the only curative option for PSC, and excellent survival rates have been reported. There is evidence that early transplantation, before end stage liver disease or cholangiocarcinoma have developed, improves the survival and quality of life of patients with PSC. Because it is the only procedure of proven benefit, patients with PSC should be considered for liver transplantation early in the course of the disease.

Biopsy, Needle↗

Motion - prophylactic banding of esophageal varices is useful: arguments against the motion.

Bleeding from esophageal varices leads to substantial morbidity and mortality. Despite advances in pharmacological and endoscopic therapy, as well as general supportive care, the mortality rate associated with acute variceal hemorrhage has not improved significantly over the past two decades. Prophylactic therapy with nonselective beta-blockers or long acting nitrates reduces the incidence of variceal bleeding in patients with cirrhosis, is cost effective and may improve survival. Surgical portosystemic shunting reduces the risk of bleeding but is associated with significant operative mortality and a high risk of portosystemic encephalopathy. Endoscopic sclerotherapy causes adverse effects in a large proportion of patients and is, therefore, not suitable for primary prophylaxis of bleeding. Although variceal band ligation is effective in reducing the rate of bleeding and is safer than sclerotherapy, it has not been shown to provide a survival advantage compared with beta-blockers. A significant reduction in the rate of variceal bleeding with band ligation, compared with beta-blockers, was shown in only one study. Beta-blockers offer several advantages, including low cost, ease of use and safety. The available data do not yet support the prophylactic use of variceal band ligation, and this procedure should be reserved for patients who are either unwilling or unable to take beta-blockers. It is hoped that additional large, multicentre trials of band ligation versus beta-blockers will examine the efficacy, cost effectiveness and impact on quality of life among patients with cirrhosis.

Adrenergic beta-Antagonists↗

Motion - colonoscopic surveillance is more cost effective than colectomy in patients with ulcerative colitis: arguments against the motion.

There are insufficient data upon which to base recommendations about surveillance colonoscopy and prophylactic colectomy for the prevention of colorectal cancer in patients with ulcerative colitis. Case series, analyses of intermediate results and extrapolations from other patient groups do not constitute reliable evidence. Available studies are susceptible to several biases: the 'healthy worker' effect, surveillance bias and selection bias. Patients who are enrolled in surveillance programs are more likely to be thoroughly evaluated beforehand, are more likely to be given a diagnosis of dysplasia or neoplasm even when asymptomatic and are more likely to comply with medical treatment, including maintenance anti-inflammatory medication. Comparisons of the rates of neoplasia or death between surveyed and nonsurveyed patients are, therefore, of questionable validity. Prophylactic colectomy, unlike surveillance colonoscopy, prevents death from colorectal cancer. Moreover, it is difficult to keep patients in surveillance programs, and those who withdraw from programs appear to be at high risk of developing cancer. Prophylactic colectomy should be strongly considered for patients with dysplasia, sclerosing cholangitis, longstanding pancolitis (especially if it began early in life) or a positive family history of colorectal cancer. This procedure is underused in clinical practice and is a good alternative to colonoscopic surveillance in high risk patients.

Colectomy↗

Motion - computerized tomographic colography is a better method for screening for polyps: arguments against the motion.

Computerized tomographic (CT) colography is an exciting technique whereby images of the colonic wall and lumen can be obtained without colonoscopy. It is not as good as conventional colonoscopy, however, because of both inherent and performance limitations. Among the former is the inability to visualize subtle mucosal lesions, such as alterations in colour or pliability. More importantly, CT colography is strictly a diagnostic technique, and does not allow biopsy or removal of polyps. The vigorous bowel preparation required for this procedure can be very unpleasant for the patient, and includes purgatives followed by distension of the colon with air. Unlike with colonoscopy, adherent stool can be difficult to distinguish radiologically from polyps or cancers; as a result, many patients require colonoscopy anyway. The major performance limitations of CT colography are poor sensitivity and specificity compared with conventional colonoscopy. Rectal lesions, flat adenomas and diminutive adenomas are especially difficult to detect, and false-positive results are also common. In addition, the procedure is expensive and less cost effective than colonoscopy. CT colography takes relatively little patient time, but a substantial amount of time is needed for the radiologist to interpret the images. Interobserver variability is high. For all of these reasons, CT colography cannot be recommended as a screening test for colorectal neoplasia.

Colonic Polyps↗

Motion--genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: arguments against the motion.

Mutations of two genes, the cystic fibrosis transmembrane conductance regulator gene (CFTR) and the pancreatic secretory trypsin inhibitor gene (PSTI), are associated with an increase in the risk of idiopathic chronic pancreatitis. Persons who have mutations of both CFTR alleles (one severely and one mildly affected) are especially susceptible to this disease. Because these compound heterozygotes have sufficient residual CFTR function, they do not develop cystic fibrosis lung disease. One PSTI mutation, N34S, independently increases the risk of pancreatitis. Thus, the risk of pancreatitis is greatest among individuals who are CFTR compound heterozygotes and who also have the PSTI mutation. Nonetheless, most people with CFTR and PSTI mutations do not develop pancreatitis. This fact indicates that environmental influences and gene-gene interactions also affect pancreatitis risk. Although CFTR and PSTI genetic testing can identify persons at an increased risk of pancreatitis, there are several reasons why the routine screening of individuals with nonhereditary pancreatitis is not recommended at this time: most disease-associated mutations are not detected by readily available techniques, genetic counselling guidelines do not exist, most patients with mutations do not develop pancreatitis and the results of testing do not affect the clinical management of pancreatitis.

Chronic Disease↗

Motion - computerized tomographic colography is a better method for screening for polyps: arguments for the motion.

Colorectal cancer is an important public health problem that is amenable to prevention and early treatment. Traditional screening techniques - fecal occult blood testing, flexible sigmoidoscopy, barium enema and colonoscopy - each have limitations in terms of diagnostic accuracy, cost and/or patient acceptability. Compliance with recommendations for screening has been poor, in part, because of negative perceptions about the available modalities. Virtual colonoscopy, or computerized tomographic colography, is a minimally invasive technique that safely evaluates the entire colon and does not require sedation. Thorough cleansing as well as immobilization and air insufflation of the colon is crucial to a successful examination. Sensitivity and specificity rates are reasonable, compared with conventional colonoscopy, and it has been shown that the latter technique can be averted in over two-thirds of cases, with few false-negative examinations. Most patients find virtual colonoscopy more acceptable than the conventional technique, and would prefer it if a repeat procedure were warranted. An economic analysis that found that computerized tomographic colography was less cost effective than conventional colonoscopy did not consider the indirect costs of the latter, which is an important limitation. Virtual colonoscopy is a novel radiological technique that may revolutionize screening for colorectal cancer.

Colonic Polyps↗

Motion--genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: arguments for the motion.

Mutations of three major genes are associated with an increased risk of acute and chronic pancreatitis: the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the pancreatic secretory trypsin inhibitor (PSTI) or serine protease inhibitor, Kazal type 1 (SPINK1) gene. Some autosomal dominant forms of hereditary pancreatitis are associated with mutations of the PRSS1 gene, which can be readily identified by genetic testing. Mutations of the CFTR gene can lead either to cystic fibrosis or to idiopathic chronic pancreatitis, and to a variety of cystic fibrosis-associated disorders, including congenital bilateral absence of the vas deferens and sinusitis. These mutations, as with those of the SPINK1 (or PSTI) gene, are prevalent in North America; thus, the presence of such a mutation in an asymptomatic person does not confer a high risk of developing pancreatitis. Combinations of mutations of the PRSS1 and SPINK1 genes lead to more severe disease, as indicated by an earlier onset of symptoms, which suggests that SPINK1 is a disease modifier. The major fear expressed by potential candidates for genetic testing is that the results could lead to insurance discrimination. Studies of the positive predictive value of genetic tests are hampered by recruitment bias and lack of knowledge of family history of pancreatitis. Genetic testing is most useful for persons for whom family members have already been found to exhibit a particular pancreatitis-associated mutation. In the future, increased knowledge of the myriad genetic causes of pancreatitis, as well as advances in the diagnosis and treatment of early chronic pancreatitis, should enhance the utility of genetic testing.

Codon↗