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Nicholas J Shaheen

Publications and source records attributed to Nicholas J Shaheen.

At least 37 records · Page 2Linked to original sources

Advances in Barrett's esophagus and esophageal adenocarcinoma.

Despite advances in diagnosis and therapy, esophageal adenocarcinoma remains an aggressive and usually lethal tumor. This review focuses on the epidemiology of esophageal adenocarcinoma and its presumed precursor lesion, Barrett's esophagus; the pathogenesis of the cancer; advances in treatment of adenocarcinoma and Barrett's esophagus; and strategies for cancer prevention. Emphasis is placed on recent literature. Although the absolute number of cases of adenocarcinoma in the United States is still small, the incidence of this cancer has increased dramatically in the last 40 years, and adenocarcinoma is now the predominant form of esophageal cancer in this country. Recent evidence suggests that Barrett's esophagus is more prevalent in asymptomatic individuals than previously appreciated. The pathogenesis of Barrett's esophagus is poorly understood. Given that some subjects will have repeated bouts of severe erosive esophagitis and never develop Barrett's esophagus, host factors must play an important role. The utility of neoadjuvant radiation and chemotherapy in those with adenocarcinoma, although they are widely practiced, is not of clear benefit, and some authorities recommend against it. Ablative therapies, as well as endoscopic mucosal resection, hold promise for those with superficial cancer or high-grade dysplasia. Most series using these modalities feature relatively short follow-up, and longer-term data will be necessary to better describe the effects of these therapies. The value of chemoprevention in subjects with dysplastic Barrett's esophagus by use of cyclooxygenase 2 inhibitors, nonsteroidal anti-inflammatory drugs, or proton pump inhibitors is unknown. Similarly, although endoscopic screening is widely practiced, its value in patients with chronic gastroesophageal reflux disease symptoms is of unproven value, and recommending bodies are divided as to its practice.

Adenocarcinoma↗

Effect of a new diagnosis of Barrett's esophagus on insurance status.

BACKGROUND: Barrett's esophagus (BE) is associated with an increased risk of adenocarcinoma of the esophagus. Despite this increased risk, most cohort studies demonstrate that the mean life expectancy of subjects with BE is no different than age-matched controls. The indirect costs associated with a diagnosis of BE are unclear. AIM: To assess the effect of a diagnosis of BE on insurance premiums. METHODS: We assessed twenty national life insurance companies (10 in southern California, 10 in North Carolina) to determine the effect of a diagnosis of BE on life insurance premiums. Our base case in Los Angeles was a 36-yr-old female nonsmoker, and in North Carolina, a 43-yr-old Caucasian male nonsmoker, both in excellent health except for a diagnosis of prevalent BE with no dysplasia. The policy requested was a 20-yr guaranteed term life insurance in the amount of $1,000,000. Companies were asked for their best price exclusive of the BE, and also their best price when considering BE as a preexisting condition. For those companies not offering the "preferred" rates, the insurance representative was subsequently sent a physician's letter explaining BE and providing data substantiating a normal life expectancy in the condition. Companies were also asked for health insurance quotes, including premiums and deductibles, inclusive and exclusive of the diagnosis of BE. RESULTS: Twenty national insurance companies were contacted. For the 43-yr-old man with no BE, the yearly "preferred" premium for life insurance averaged $1,255. The mean cost of the policies offered to the same individual with BE as a preexisting condition was $2,731 (p < 0.001). For the 36-yr-old female the base rate exclusive of BE was $517, with a range of $472-$551. After inclusion of the diagnosis of BE, the mean rate rose by 177%, to $1,434, with a range of $1,144-$1,896. Companies either refused to provide health insurance to the individual with BE or would not provide a quote without review of the medical record. None of the insurance companies changed their quoted rates after receiving the letter written by the physician on behalf of the individual. CONCLUSIONS: Despite the preponderance of data demonstrating a normal life expectancy associated with the condition, a diagnosis of BE more than doubles life insurance premiums, and impacts the availability of health insurance. Further steps to educate insurance companies about the risks associated with BE are warranted, and patients should understand this additional "risk" of endoscopic screening for BE. There are significant indirect costs associated with a diagnosis of BE.

Adult↗

Does fundoplication change the risk of esophageal cancer in the setting of GERD?

The effect of a surgical antireflux procedure on the risk of cancer in those with GERD and Barrett's esophagus is unclear. Although some authorities have suggested that a surgical antireflux procedure might be superior to medical management for the prevention of cancer, the cumulative data do not demonstrate that those patients undergoing surgery have any decrement in cancer risk compared to those who receive medication. Most data available to assess the effect of surgery on cancer risk come from case series. These data are of very limited utility, because of differences in the baseline composition of groups undergoing medical and surgical therapy. Until more data are available, patients should not be advised to undergo surgical fundoplication as an antineoplastic measure.

Barrett Esophagus↗

Digestive and liver diseases statistics, 2004.

BACKGROUND & AIMS: Digestive and liver diseases are associated with substantial morbidity and mortality in the United States. Statistics about the incidence, prevalence, mortality, and resource utilization of digestive and liver diseases in the United States may be cumbersome to obtain because they are scattered in multiple sources. These data may be useful for policy makers, grant applicants, and authors. METHODS: Data on the most common gastrointestinal and liver diseases were collected from large publicly available national databases. Information was collected on inpatient and outpatient gastrointestinal complaints and diagnoses, gastrointestinal cancers, and deaths from common liver diseases. RESULTS: The leading gastrointestinal complaint prompting an outpatient visit is abdominal pain, with 12.2 million annual visits, followed by diarrhea, nausea, and vomiting. Abdominal pain is the leading outpatient gastrointestinal diagnosis, accounting for 5.2 million visits annually, followed by gastroesophageal reflux disease, with 4.5 million visits. Gallstone disease is the most common inpatient diagnosis, with 262,411 hospitalizations and a median inpatient charge of USD$11,584. Colorectal cancer is the most common gastrointestinal cause of death and is the most common gastrointestinal cancer, with an incidence of 54 per 100,000. Among gastrointestinal cancers, primary liver cancer had the highest increase in incidence from 1992 to 2000. CONCLUSIONS: Gastrointestinal and liver diseases are associated with significant outpatient and inpatient healthcare utilization. Following trends in utilization is important for determining allocation of resources for health care and research.

Biliary Tract Diseases↗

A critical review of the diagnosis and management of Barrett's esophagus: the AGA Chicago Workshop.

BACKGROUND & AIMS: The diagnosis and management of Barrett's esophagus (BE) are controversial. We conducted a critical review of the literature in BE to provide guidance on clinically relevant issues. METHODS: A multidisciplinary group of 18 participants evaluated the strength and the grade of evidence for 42 statements pertaining to the diagnosis, screening, surveillance, and treatment of BE. Each member anonymously voted to accept or reject statements based on the strength of evidence and his own expert opinion. RESULTS: There was strong consensus on most statements for acceptance or rejection. Members rejected statements that screening for BE has been shown to improve mortality from adenocarcinoma or to be cost-effective. Contrary to published clinical guidelines, they did not feel that screening should be recommended for adults over age 50, regardless of age or duration of heartburn. Members were divided on whether surveillance prolongs survival, although the majority agreed that it detects curable neoplasia and can be cost-effective in selected patients. The majority did not feel that acid-reduction therapy reduces the risk of esophageal adenocarcinoma but did agree that nonsteroidal antiinflammatory drugs are associated with a cancer risk reduction and are of promising (but unproven) value. Participants rejected the notion that mucosal ablation with acid suppression prevents adenocarcinoma in BE but agreed that this may be an appropriate strategy in a subgroup of patients with high-grade dysplasia. CONCLUSIONS: Based on this review of BE, the opinions of workshop members on issues pertaining to screening and surveillance are at variance with published clinical guidelines.

Adenocarcinoma↗

Screening for upper gastrointestinal tract malignancies.

The screening for malignancies involving the upper gastrointestinal (GI) tract has taken on new importance as the incidence of cancers such as adenocarcinoma of the esophagus has risen. The availability of new screening technology and molecular biological techniques has dramatically improved our ability to detect early lesions. We have also developed a detailed understanding of the natural history of many upper GI malignancies. This new knowledge has led to significant improvement in population-based screening programs. In this review we will detail the evidence supporting our current screening methods and provide a concise overview of current screening recommendations for select upper GI malignancies.

Adenocarcinoma↗

Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer.

BACKGROUND: Iron is a pro-oxidant that may promote carcinogenesis. Mutations in the hemochromatosis (HFE) gene are associated with increased total body iron stores in some individuals. We assessed the risk of colon cancer among individuals with and without HFE gene mutations. METHODS: We performed a population-based, case-control study in North Carolina. Case patients with colon cancer and control subjects provided information on multiple environmental exposures, including total iron intake and nonsteroidal anti-inflammatory drug (NSAID) use. They also provided a venous blood sample, from which DNA was extracted, amplified, and subjected to diagnostic restriction enzyme mapping to detect two major HFE gene mutations, C282Y and H63D. Data were analyzed with Fisher's exact test and logistic regression. All statistical tests were two-sided. RESULTS: Thirteen hundred and eight subjects participated (475 case patients, 833 control subjects). The allele frequencies of the H63D and C282Y mutations were greater among case patients (0.11 and 0.046, respectively) than among control subjects (0.09 and 0.044, respectively; P =.14 and P =.85, respectively). When we controlled for age, race, sex, red meat consumption, NSAID use, and total iron intake, subjects with any HFE gene mutation were more likely to have colon cancer than subjects with no HFE gene mutations (adjusted odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.07 to 1.87). The magnitude of the effect was similar for both the H63D (adjusted OR = 1.44, 95% CI = 1.04 to 1.98) and C282Y mutations (adjusted OR = 1.39, 95% CI = 0.88 to 2.19). The risk of colon cancer associated with an HFE gene mutation was similar for those who did and did not have a family history of colon cancer. Among those with HFE mutations, cancer risk increased with increasing age and total iron intake. CONCLUSIONS: HFE gene mutations are associated with an increased risk of colon cancer. Cancer risk is greatest in mutation carriers who are older or consume high quantities of iron.

Age Factors↗

Fundoplication improves disordered esophageal motility.

Patients with gastroesophageal reflux disease (GERD) and disordered esophageal motility are at risk for postoperative dysphagia, and are often treated with partial (270-degree) fundoplication as a strategy to minimize postoperative swallowing difficulties. Complete (360-degree) fundoplication, however, may provide more effective and durable reflux protection over time. Recently we reported that postfundoplication dysphagia is uncommon, regardless of preoperative manometric status and type of fundoplication. To determine whether esophageal function improves after fundoplication, we measured postoperative motility in patients in whom disordered esophageal motility had been documented before fundoplication. Forty-eight of 262 patients who underwent laparoscopic fundoplication between 1995 and 2000 satisfied preoperative manometric criteria for disordered esophageal motility (distal esophageal peristaltic amplitude < or =30 mm Hg and/or peristaltic frequency < or =80%). Of these, 19 had preoperative manometric assessment at our facility and consented to repeat study. Fifteen (79%) of these patients had a complete fundoplication and four (21%) had a partial fundoplication. Each patient underwent repeat four-channel esophageal manometry 29.5 +/- 18.4 months (mean +/- SD) after fundoplication. Distal esophageal peristaltic amplitude and peristaltic frequency were compared to preoperative data by paired t test. After fundoplication, mean peristaltic amplitude in the distal esophagus increased by 47% (56.8 +/- 30.9 mm Hg to 83.5 +/- 36.5 mm Hg; P < 0.001) and peristaltic frequency improved by 33% (66.4 +/- 28.7% to 87.6 +/- 16.3%; P < 0.01). Normal esophageal motor function was present in 14 patients (74%) after fundoplication, whereas in five patients the esophageal motor function remained abnormal (2 improved, 1 worsened, and 2 remained unchanged). Three patients with preoperative peristaltic frequencies of 0%, 10%, and 20% improved to 84%, 88%, and 50%, respectively, after fundoplication. In most GERD patients with esophageal dysmotility, fundoplication improves the amplitude and frequency of esophageal peristalsis, suggesting refluxate has an etiologic role in motor dysfunction. These data, along with prior data showing that postoperative dysphagia is not common, imply that surgeons should apply complete fundoplication liberally in patients with disordered preoperative esophageal motility.

Adult↗

Insurance, employment, and psychosocial consequences of a diagnosis of hereditary hemochromatosis in subjects without end organ damage.

OBJECTIVES: Asymptomatic individuals with hereditary hemochromatosis (HH) may experience difficulties in obtaining employment or insurance, despite their good health. The extent to which these difficulties occur is unclear. The aim of this study was to assess the insurance, employment, and psychosocial consequences of a diagnosis of HH in subjects with no end organ damage. METHODS: In three outpatient clinics specializing in the treatment of HH, we performed a survey of individuals diagnosed with HH who were without end organ damage secondary to iron overload, along with their unaffected siblings. A review of the medical records of subjects with HH was performed. Main outcomes were attaining and keeping employment; health, disability and life insurance; and scores on the SF-36, a quality of life measure, and the SCL-90-R, a measure of psychological well-being. RESULTS: Of 130 eligible subjects with HH, 126 (97%) responded. Of the 55 eligible controls, 46 (84%) responded. Of the 126 subjects with HH, 25 (20%) described 28 incidents of insurance denial or increased premium rates, which they attributed to their diagnosis HH. Of the 28 incidents, 16 (57%) involved life insurance, eight (29%) involved health insurance, and four (14%) involved disability insurance. One subject reported an employment refusal. Five of the 25 subjects (20%) reporting insurance denial or increased premiums had significant comorbid conditions. One of 46 sibling controls (2%) reported an increased rate for life insurance (p = 0.003). No differences were noted in either the SF-36 or the SCL-90-R scores between subjects with HH and unaffected siblings. Overall rates of active health, disability, and life insurance were similar between the groups. CONCLUSIONS: Insurance denial and increased premium rates are reported commonly among individuals with HH without end organ damage. However, the overall proportion of those with active insurance, the quality of life, and the psychological well-being of these subjects were similar to those of unaffected siblings.

Adult↗

The risk of end stage liver disease and hepatocellular carcinoma among persons infected with hepatitis C virus: publication bias?

OBJECTIVES: In persons infected with hepatitis C virus (HCV), the incidence of cirrhosis and hepatocellular carcinoma (HCC) can be estimated by examining over time entire cohorts with known onset of HCV infection. We performed a systematic review of the literature to identify and to analyze studies that examine such cohorts. METHODS: A search of all articles from 1980 to 2001 was performed. Published studies were included in which chronic HCV infection was defined by elevation of liver enzymes or persistent RNA. We excluded studies in which cohorts were selected from patients with prevalent liver disease or in whom the onset of infection could not be estimated. Two investigators abstracted the data. The incidences of cirrhosis and HCC were analyzed in all studies and in categories based on study design, mode of HCV acquisition, sample size and duration of follow-up, age at the onset of infection, and the quality of estimating the onset of HCV infection. RESULTS: Of the articles, 21 fulfilled the selection criteria. Studies varied in sample size (17-1,680), duration of follow-up (8-45 yr), total person-years (157-34,098), and the mean age at onset of HCV (5-58 yr). The mean time to end stage liver disease (ESLD) was 4-23 yr and to HCC was 9-31 yr. A funnel plot showed a possible publication bias against studies with low incidence of ESLD and HCC. The pooled weighted incidence rates for ESLD and HCC based on infection mode were as follows: community-acquired HCV, 1.9 and 0 per 1,000 person-years; transfusion associated, 4.5 and 0.7; hemophilia patients, 7.9 and 1.0; anti-D IgG, 0.7 and 0 per 1,000 person-years. Poisson regression modeling showed that the incidence of ESLD is increased in studies with a low quality estimate of the onset of HCV infection, in community-acquired and transfusion-associated HCV, and in studies with prospective design. CONCLUSIONS: We found large variation in the incidence estimates of cirrhosis and HCC. Short duration of follow-up, small sample size, and possible publication bias may explain some of this variation. Low quality estimates of the onset of HCV infection, a prospective study design, and a transfusion- or hemophilia-related mode of acquisition were independent predictors of high reported incidence of ESLD.

Bias↗

Does a surgical antireflux procedure decrease the incidence of esophageal adenocarcinoma in Barrett's esophagus? A meta-analysis.

OBJECTIVE: The risk of adenocarcinoma of the esophagus is increased among those with Barrett's esophagus (BE). Whether the risk of cancer in the setting of BE can be decreased by a surgical antireflux procedure (SARP) is unclear. This study compared the reported incidence of esophageal adenocarcinoma in subjects with BE who underwent SARP with those with BE who had medical management. METHODS: We used MEDLINE to perform a meta-analysis of the English language literature published from 1966 through October 2001. We reviewed abstracts found with the search term "Barrett's esophagus" and the following: "adenocarcinoma," "esophageal neoplasm," "proton pump inhibitor," "fundoplication," or "antireflux procedure." Study entry criteria included 1) trial or cohort study with a report of cancer risk expressible in cancers per patient-year, 2) histologic confirmation of BE and any adenocarcinomas, and 3) adequate description of intervention (medical vs SARP). Data were abstracted by two reviewers using standardized forms. Subgroup comparisons were made using only medical management studies published in the last 5 yr. Multivariable regression controlling for subject age, country of origin, and BE length was performed. RESULTS: We reviewed 1247 abstracts, and 34 met the inclusion criteria. There were a cumulative 4678 patient-years of follow-up in the SARP group and 4906 patient-years in the medical group. The cancer incidence rate in the SARP group was 3.8 cancers/1000 patient-years, compared with 5.3 in the medical group (p=0.29). Similarly, there was no significant difference between cancer rates when comparing SARP with medical series reported in the last 5 yr (3.8/1000 patient-years vs 4.2/1000 patient-years, p=0.33). Multivariate analysis controlling for subject age, country of origin, and BE length did not alter these findings. CONCLUSION: The reported risk of adenocarcinoma in subjects with BE is low and not significantly decreased by a surgical antireflux procedure. Antireflux surgery in the setting of BE should not be recommended as an antineoplastic measure.

Adenocarcinoma↗