Burden of Digestive Diseases in the United States Part I: Overall and Upper Gastrointestinal Diseases

Mini-Reviews and Perspectives Burden of Digestive Diseases in the United States Part I: Overall and Upper Gastrointestinal Diseases JAMES E. EVERHART, and CONSTANCE E. RUHL Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; Social & Scientific Systems, Inc., Silver Spring, Maryland

Introduction to Series Digestive, liver, and pancreatic diseases have a far-reaching medical, economic, social, and political impact on society in the United States and worldwide. We believe it is important to highlight salient features as well as key tables/figures from the Burden of Digestive Diseases in the United States report developed as part of the National Commission on Digestive Diseases of the National Institutes of Health. The commission was created, in part, due to the advocacy efforts of the AGA. Divided into three segments, this series, spanning consecutive issues in Gastroenterology, will be informative and illuminating. The series will provide investigators, clinicians, and other readers with the necessary tools to generate new hypotheses, craft new directions of broad-based and integrated research, and make informed clinical conclusions. Hashem B. El-Serag Associate Editor Anil K. Rustgi Editor

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his review presents a synthesis and excerpts from a project to determine the burden of digestive diseases in the United States.1 The full report, available at http:// www2.niddk.nih.gov/, includes the methodology and description of all surveys used. In addition, a list of all International Classification of Disease (ICD) codes for digestive diseases is found in an online appendix (www. gastrojournal.org). This first article in a series of 3 covers the overall burden of digestive diseases and that of selected upper gastrointestinal (GI) conditions. The second article will address the burden of lower GI diseases and the third article will cover the burden of liver, gallbladder, and pancreatic diseases.

All Digestive Diseases Medical Care In 2004, there were an estimated 72 million ambulatory care visits with a first-listed diagnosis of a digestive disease and ⬎104 million visits with an all-listed diagnosis, which equated to a rate of 35,684 visits per 100,000 US population (Table 1). In other words, for every 100 US residents, there were 35 ambulatory care visits at which a digestive disease diagnosis was noted. Visits were common for all age groups, with the highest rate among people age ⱖ65 years. Age-adjusted rates were comparable for blacks and whites and were 20% higher for females than for males. Digestive diseases were common diagnoses at hospital discharge with approximately 4.6 million discharges of patients with a first-listed diagnosis of a digestive disease and 13.5 million discharges with a digestive disease as primary first or secondary diagnosis (Table 1). With a rate of allGASTROENTEROLOGY 2009;136:376 –386

listed diagnoses of 4,608 per 100,000 in 2004, there were nearly 5 overnight hospital stays per 100 US residents that included a discharge diagnosis of ⱖ1 digestive disease. These rates were nearly as high among children as among middle-aged adults and were higher in these 2 age groups than among younger adults. The highest rate was among people age ⱖ65 years. In contrast with their ambulatory care visits, blacks had higher rates of hospitalization than did whites. Comparable or lower age-adjusted rates of ambulatory care visits among blacks, yet higher rates of hospitalization, were a common finding for a number of digestive diseases. Women had a 10% higher age-adjusted rate than men. The rate of ambulatory care visits over time (age-adjusted to the 2000 US population) is shown in Figure 1 by 3-year periods (except for the first period, which was 2 years), between 1992 and 2005. Age-adjusted rates increased during this period by one third, from 26.4 to 35.3 per 100 population. This trend in increased rates of ambulatory care visits started at least as early as 1985, when there were 22.4 digestive disease diagnoses per 100 population.2 Rates of all-listed hospitalization with a digestive disease diagnosis fell between 1983 and 1988, a pattern that occurred for all hospitalizations in the United States. Hospitalization rates were stable for the next 10 years before rising to a rate in 2004 equal to the previous peak rate in 1982. The ageadjusted percent increase between 1998 and 2004 was 35%. © 2009 by the AGA Institute

0016-5085/09/$36.00 doi:10.1053/j.gastro.2008.12.015

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Table 1. All Digestive Diseases: Number and Age-Adjusted Rates of Ambulatory Care Visits and Hospital Discharges with First-Listed and All-Listed Diagnoses by Age, Race, and Sex in the United States, 2004 Ambulatory care visits First-listed diagnosis Demographic characteristics Age (years) ⬍15 15–44 45–64 ⱖ65⫹ Race White Black Gender Female Male Total

Hospital discharges

All-listed diagnoses

First-listed diagnosis

All-listed diagnoses

Number in thousands

Rate per 100,000

Number in thousands

Rate per 100,000

Number in thousands

Rate per 100,000

Number in thousands

Rate per 100,000

10,951 21,348 21,430 18,342

18,010 16,967 30,314 50,483

15,170 28,749 32,434 28,437

24,948 22,848 45,880 78,268

331 1112 1362 1779

544 884 1926 4897

2321 2401 3489 5313

3817 1908 4935 14,622

59,506 8733

24,317 24,076

85,798 13,339

34,953 37,784

3526 531

1412 1655

10,242 1702

4108 5142

39,531 32,540 72,071

25,827 23,017 24,543

59,553 45,236 104,790

38,648 32,159 35,684

2545 2023 4591

1592 1483 1563

7593 5909 13,533

4753 4335 4608

Source: National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (3-year average, 2003–2005), and Healthcare Cost and Utilization Project Nationwide Inpatient Sample.

This overall increase was the net of diagnoses whose rates increased and diagnoses whose rates decreased. The recent increase in overnight hospital stays with a diagnosis of digestive disease was in contrast with a more modest rate of increase of 13.3% for hospital discharges for all diseases. In 1998, 25.3% of all hospital discharges had a diagnosis of digestive diseases, which increased to 30.1% in 2004. Thus, rates of hospitalizations with digestive disease diagnoses increased both absolutely and as a proportion of all hospitalizations. The largest contributor to the increase in hospitalizations was from “other digestive diseases”—those conditions that do not have separate chapters in the Burden report. The largest contributions by individual disease were made by gastroesophageal reflux disease (GERD), with an increase over this period of 376 per 100,000 population; viral hepatitis C, with 79 per 100,000; chronic constipation, with 62 per 100,000; intestinal infections, with 41 per 100,000; and pancreatitis, with 23 per 100,000. Except for pancreatitis, each of these diagnoses was more likely to be listed as a

secondary discharge diagnosis than as the first-listed diagnosis. A few common conditions declined as reasons for overnight hospitalizations, notably peptic ulcer disease (owing to decreased frequency) and gallstones (owing to shift to same-day surgery).

Mortality In 2004, there were ⬎236,000 deaths in the United States with a digestive disease as the underlying cause (Table 2), which represented 9.8% of all deaths. A disproportionately lower proportion of deaths from digestive diseases occurred among children (4.1%) and a higher proportion occurred among middle-aged adults (15.1%). There was no major variation in the distribution of deaths from digestive disease as a proportion of all deaths by race or gender. However, blacks had a 29% higher death rate than whites, and men had a 53% higher rate than women. Years of potential life lost (YPLL) before age 75 years is the addition of the number of years before age 75 at which deaths occur. A death at age 55 years, for example, contributes 20 YPLL,

Figure 1. All digestive diseases: age-adjusted rates of ambulatory care visits and hospital discharges with all-listed diagnoses in the United States, 1979 –2004. (Source: National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey [averages 1992–1993, 1994 –1996, 1997–1999, 2000 – 2002, 2003–2005], and National Hospital Discharge Survey.) 377

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Table 2. All Digestive Diseases: Number and Age-Adjusted Rates of Deaths, Years of Potential Life Lost (YPLL; to Age 75), and Digestive Disease as a Percentage of All Deaths by Age, Race, and Sex in the United States, 2004 Underlying cause

Demographic characteristics Age (years) ⬍15 15–44 45–64 ⱖ65 Race White Black Gender Female Male Total

Underlying or other cause

Number of deaths

Rate per 100,000

YPLL in thousands

Digestive disease as a percentage of all deaths

Number of deaths

Rate per 100,000

1612 11,036 66,806 156,706

2.7 8.8 94.5 431.3

118.2 397.3 1263.8 228.2

4.1 6.9 15.1 8.9

2908 17,915 92,862 252,709

4.8 14.2 131.4 695.5

200,834 27,812

77.0 99.5

1579.4 340.2

9.8 9.7

313,055 42,514

119.7 152.7

111,264 124,900 236,164

63.6 97.1 80.4

723.3 1284.2 2007.5

9.2 10.6 9.8

177,811 188,596 366,407

100.7 149.1 124.8

Source: Vital Statistics of the United States.

whereas a death at age 75 years contributes none. There were 2 million YPLL before age 75 years owing to digestive diseases, representing 8.5 years per death with digestive disease as an underlying cause. Digestive diseases were more frequently listed as underlying cause than as contributing cause, mainly owing to the large effect of deaths from cancer, which was usually listed as underlying cause. A gradual decline occurred in digestive disease mortality between 1979 and 2004, both as underlying (18.2%) and as underlying or other cause (20.3%; Figure 2). There were many contributions to this decline, but the greatest determinant was the decrease in digestive disease cancer mortality by 19.8% as underlying cause and 24.0% as underlying or contributing (other) cause. Summary data for individual digestive diseases are shown in Table 3, ordered by underlying cause of death and type of disease. Five diseases each caused ⬎10,000 deaths. These were liver disease and 4 cancers, led by colorectal cancer. Two common causes of death were

transmissible infectious diseases: GI infections and viral hepatitis C. Chronic viral hepatitis is also a significant contributor to liver and bile duct cancers, which accounted for ⬎11,000 deaths. Malignancies were responsible for 6 of the top 10 digestive diseases that contributed the most to YPLL. Acute and chronic liver disease was the second leading cause of death (after colorectal cancer), but contributed the greatest number of YPLL. Also among the 10 leading causes of YPLL were hepatitis C and pancreatitis. The distribution of burden of medical care for digestive diseases was notably different from mortality from digestive diseases. The 6 leading diseases with diagnosis noted at ambulatory care visits were GERD, chronic constipation, abdominal wall hernia, hemorrhoids, diverticular disease, and irritable bowel syndrome (IBS). At least 3 of these (GERD, constipation, and IBS) are caused largely by disordered function of the GI tract, and diverticular disease also may be in part a consequence of

Figure 2. All digestive diseases: age-adjusted rates of death in the United States, 1979 –2004. Switch from ICD-9 to ICD-10 occurred in 1999. (Source: Vital Statistics of the United States.) 378

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Table 3. Burden of Selected Digestive Diseases in the United States, 2004 Digestive disease

Deaths, underlying cause*

YPLL to age 75 years*

Ambulatory care visits, all-listed diagnoses†

Hospital discharges, all-listed diagnoses‡

All digestive diseases All digestive cancers Colorectal Pancreatic Esophageal Gastric Primary liver Bile duct Gallbladder Small intestine Liver disease All viral hepatitis Hepatitis C Hepatitis B Hepatitis A GI infections Peptic ulcer disease Pancreatitis Diverticular disease Abdominal wall hernia GERD Gallstones Inflammatory bowel disease Crohn’s disease Ulcerative colitis Appendicitis All functional disorders Chronic constipation IBS Hemorrhoids

236,164 135,107 53,815 31,800 13,667 11,253 6323 4954 1939 1115 36,090 5393 4595 645 58 4396 3692 3480 3372 1,172 1150 1092 933 622 311 453 423 137 20 14

2,007,500 945,200 340,200 206,800 113,800 84,200 72,400 32,900 10,900 9300 559,100 101,800 87,500 11,800 800 12,800 19,700 42,800 8600 6900 6000 4400 9100 7000 2000 5000 2500 900 0 200

104,790,000 4,198,000 2,677,000 415,000 372,000 141,000 63,000 — — — 2,398,000 3,510,000 2,747,000 729,000 — 2,365,000 1,473,000 881,000 3,269,000 4,787,000 18,342,000 1,836,000 1,892,000 1,176,000 716,000 782,000 11,648,000 6,306,000 3,054,000 3,275,000

13,533,000 726,000 264,000 68,000 44,000 31,000 33,000 17,000 6000 9000 759,000 475,000 419,000 69,000 10,000 450,000 489,000 454,000 815,000 372,000 3,189,000 622,000 221,000 141,000 82,000 325,000 1,241,000 700,000 212,000 306,000

Sources: *Vital Statistics of the United States; †National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey; Cost and Utilization Project Nationwide Inpatient Sample.

‡Healthcare

dysfunction. The 6 most common digestive disease diagnoses on hospital discharge records were GERD, diverticular disease, liver disease, constipation, gallstones, and peptic ulcer disease. The main difference between the records for hospital discharge diagnoses and ambulatory care diagnoses was the high numbers of diagnoses with liver disease and peptic ulcer disease, which can be life threatening, and gallstones, which are a common reason for surgery. Because GERD and constipation should rarely lead to hospitalization, it must be assumed that when listed on discharge, they either contributed to the reason for hospitalization or were listed in thousands of discharges simply because they were so common.

Prescriptions The 10 costliest prescription drugs from retail pharmacies for digestive diseases, according to the 2004 Verispan database of retail pharmacy sales, are shown in Table 4. Five proton pump inhibitors dominated the prescription market, at 50.7% of total number of prescriptions and 77.3% of total cost; they were mainly prescribed for GERD. The other most costly medications were

mesalamine for inflammatory bowel disease, ranitidine (another acid-suppressing agent), tegaserod (for IBS and constipation), and ribavirin and peginterferon alfa-2a (for hepatitis C virus [HCV] infection). A major deficiency of the drug data is lack of information on nonprescription medications, complementary and alternative medications, infusions, mail-order drugs, and drugs administered in the hospital.

Costs of Digestive Diseases Costs of digestive diseases were estimated using the human capital approach, which includes the value of resources used for medical care (direct costs) and those forgone owing to time lost from work and leisure (indirect costs).3,4 Where possible, an attempt was made to provide cost estimates by ICD codes for each digestive disease with a substantial economic impact. A conservative approach was taken toward estimation of economic costs. Direct costs represent charges for hospital services, physician services, prescription drugs, over-the-counter drugs, nursing home care, home health care, hospice care, 379

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Table 4. All Digestive Diseases: Costliest Prescriptions Prescription

Retail cost

Drug

Number (Million)

%

$ Million

%

Lansoprazole Esomeprazole Pantoprazole Rabeprazole Omeprazole Mesalamine Ranitidine Tegaserod Ribavirin Peginterferon alfa-2a Other Total

21.00 19.46 11.72 8.02 8.58 2.45 13.17 1.62 0.22 0.13 49.38 135.74

15.5 14.3 8.6 5.9 6.3 1.8 9.7 1.2 0.2 0.1 36.4 100

3104.9 2845.6 1408.2 1135.8 1038.6 468.5 319.4 238.0 229.3 191.7 1351.4 12,331.7

25.2 23.1 11.4 9.2 8.4 3.8 2.6 1.9 1.9 1.6 11.0 100

Source: Verispan.

and outpatient endoscopy. The total direct costs for digestive diseases were $97.8 billion (Table 5), of which the largest component was hospital facility costs ($40.6 billion). Facility charges for first-listed diagnoses were 86% of the total hospital charges. Diseases with ⬎$1 billion in facility charges were gallstones ($4.3), abdominal wall hernia ($3.5 billion), diverticular disease ($2.2 billion), pancreatitis ($2.0 billion), colorectal cancer ($1.9 billion), appendicitis ($1.9 billion), liver disease ($1.8 billion), GERD ($1.5 billion), and peptic ulcer disease ($1.4 billion). Total physician charges associated with hospital services for digestive diseases were $14.7 billion. However, only $8.5 billion of this total could be attributed to individual digestive diseases. The largest physician charges were for GERD ($0.77 billion), gallstones ($0.75 billion) and abdominal wall hernia ($0.54 billion). Ambulatory care costs consist of physician fees for office visits plus any extra charges for procedures performed in their offices. Total ambulatory care costs (excluding ambulatory surgery) were $16.0 billion, with the largest contributors being abdominal wall hernia ($1.5 billion), GERD ($1.40 billion), chronic constipation ($0.63 billion), gallstones ($0.62 billion), and diverticular disease ($0.55 billion). Expenditures for prescription drugs written by physicians during an office visit were estimated to be $12.3 billion (Table 4). Over half of this cost ($7.7 billion) was associated with drugs prescribed for GERD and peptic ulcer disease, with other major contributions made by drugs prescribed for HCV, IBS, and inflammatory bowel diseases. Smaller contributions to direct costs were made by nursing home ($3.3 billion), home health care ($3.1 billion), and hospice care ($1.9 billion). Three additional categories of direct costs could not be distributed among individual digestive diseases: services provided by primarily hospital-based specialties (anesthesiology, radiology, and pathology), estimated to be $6.3 billion; outpatient endoscopy, estimated to be 380

$3.7 billion; and over-the-counter drugs (for GERD, constipation, and diarrhea) estimated to be $2.1 billion. Of the $85.7 billion in direct costs that could be attributed to individual digestive diseases, the 10 largest contributors were GERD ($12.1 billion), gallstones ($5.8 billion), abdominal wall hernia ($5.7 billion), colorectal cancer ($4.0 billion), diverticular disease ($3.6 billion), peptic ulcer disease ($2.6 billion), pancreatitis ($2.5 billion), liver disease ($2.5 billion), appendicitis ($2.3 billion), and chronic constipation ($1.6 billion). Together, these 10 diseases cost $42.8 billion, which represented 50% of expenditures assigned to individual diseases. As a group, cancers accounted for $8.4 billion, or 10% of the direct costs assigned to individual diseases. Indirect costs comprise the implicit value of forgone earnings or production owing to (1) consumption of

Table 5. Direct, Indirect, and Total Costs of Digestive Diseases in the United States, 2004 ($ Millions) Digestive disease GI infections Hepatitis A Hepatitis B Hepatitis C Other viral hepatitis All viral hepatitis Esophageal cancer Gastric cancer Cancer of small intestine Colorectal cancer Liver cancer Bile duct cancer Gallbladder cancer Pancreatic cancer Other digestive cancers All digestive cancers Hemorrhoids GERD Peptic ulcer disease Chronic constipation IBS Other functional disorders All functional disorders Appendicitis Abdominal wall hernia Crohn’s disease Ulcerative colitis All inflammatory bowel disease Diverticular disease Liver diseases Gallstones Pancreatitis Other digestive diseases All digestive diseases Total costs that could not be allocated to specific conditions Total

Direct costs Indirect ($) costs ($)

Total ($)

$1343.4 14.5 204.6 1065.5 15.9 1300.5 597.3 487.5 123.8 4043.7 261.2 166.0 66.6 1077.4 1618.0 8441.5 775.8 12,125.0 2599.9 1572.1 949.8 1139.3 3661.2 2310.6 5698.9 1071.0 767.9 1838.9 3569.3 2532.0 5763.6 2546.2 31,193.0 85,699.7 12,118.1

$392.5 $1735.9 18.5 32.9 253.2 457.9 1783.6 2849.1 32.0 47.9 2087.3 3387.8 1975.4 2,572.6 1415.0 1902.6 159.9 283.8 5455.2 9498.9 1318.6 1579.8 515.5 681.5 150.6 217.2 3225.6 4303.0 1490.9 3108.9 15,706.7 24,148.2 97.6 873.4 515.0 12,639.9 518.7 3118.6 140.4 1712.5 57.5 1007.3 129.7 1269.0 327.7 3988.8 356.3 2666.8 371.9 6070.8 227.9 1298.9 100.1 868.0 328.0 2166.9 471.9 4041.2 10,563.0 13,095.0 406.2 6169.7 1187.1 3733.3 7102.2 38,295.2 40,432.0 126,131.7 3576.4 15,694.5

97,817.9

44,008.4 141,826.3

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Table 6. Most Common Indications and Findings for Esophagogastroduodenoscopy % of examsa Indications Symptoms Reflux symptoms/heartburn Alarm symptoms GERD Dyspepsia/abdominal pain Dysphagia Bleeding cluster Abdominal pain/bloating Anemia Dyspepsia Nausea Vomiting Surveillance/screening Barrett’s esophagus Varices Findings Normal examination Mucosal abnormality Hiatal hernia Esophageal inflammation Stricture/stenosis Barrett’s esophagus Ulcer Polyp Varices

28.3 27.7b 22.3c 21.6d 20.5 20.4e 20.1 10.5 9.7 6.7 4.9 4.6 1.8 41.5 38.8 33.4 17.8 9.9 6.7 6.3 4.5 2.8

Source: Clinical Outcomes Research Initiative’s National Endoscopic Database. aCategories are not mutually exclusive. bAlarm symptoms: weight loss, vomiting, bleeding cluster. cGERD: reflux symptoms, excluding dysphagia and surveillance of Barrett’s esophagus. dDysphagia/abdominal pain: dyspepsia and/or abdominal pain/bloating, excluding reflux symptoms; dysphagia and surveillance of Barrett’s esophagus. eBleeding cluster: anemia, iron deficiency, melena, hematemesis, hematochezia, positive fecal occult blood test, suspected upper GI bleeding.

hospital or ambulatory care, (2) premature death, and (3) additional work loss associated with acute and chronic digestive diseases. Also included is the value of leisure time lost owing to morbidity and mortality. The total indirect costs were $44.0 billion (Table 5), with almost three quarters of this cost due to mortality ($32.8 billion). Those contributors of ⱖ$1 billion in mortality indirect costs were liver disease ($10.2 billion), colorectal cancer ($5.2 billion), pancreatic cancer ($3.2 billion), esophageal cancer ($1.9 billion), HCV ($1.7 billion), gastric cancer ($1.4 billion), and primary liver cancer ($1.3 billion). Because of their high fatality rate, digestive tract cancers accounted for a large proportion of the mortality costs (46%). The lost wages were $5.8 billion owing to hospital stays and $1.9 billion owing to ambulatory visits. A major source of indirect costs that could not be assigned to individual digestive diseases was the cost of work and leisure loss from acute and chronic conditions

that did not result in a physician outpatient visit or hospitalization, estimated to be $3.6 billion. The total estimated cost of digestive diseases, including direct and indirect, in the United States in 2004 was $141.8 billion (Table 5). Direct costs accounted for 69% of the total. The majority of costs (88% of direct and 92% of indirect) were assigned to specific digestive diseases. In total cost, the 10 most costly diseases were liver disease ($13.1 billion), GERD ($12.6 billion), colorectal cancer ($9.5 billion), gallstones ($6.2 billion), abdominal wall hernia ($6.1 billion), pancreatic cancer ($4.3 billion), diverticular disease ($4.0 billion), pancreatitis ($3.7 billion), peptic ulcer disease ($3.1 billion), and viral hepatitis C ($2.8 billion) These cost calculations have significant limitations that resulted in underestimates of cost: (1) federal hospitals and physicians (including the armed services, Department of Veterans Affairs, and the Indian Health Service) were not included. These entities provide approximately 10% of care in the United States.4 (2) Physician costs for both procedures and inpatient and outpatient visits were based on Medicare reimbursement rates, which are generally lower than rates of other payers. (3) Over-the-counter drug data did not include all categories of digestive disease drugs. (4) Indirect costs of acute and chronic conditions that did not result in medical care did not include data for all digestive diseases. The greatest gap was for work loss from GI infections that did not result in medical care. Using independent sources not available now, the estimate in 1985 was ⬎$4 billion.4 (4) Indirect costs did not include work loss owing to disability, for which we had no data. Two previous estimates of the costs of digestive diseases in the United States have used the same approach to compiling costs, but with varied sources of data.4,5 The estimated direct costs of digestive diseases in 1985 were $41.5 billion and $85.5 billion in 1998. As a result of the limitations noted, the true costs of digestive diseases in the United States in the current report are underestimated. The total direct cost of health care spending for all diseases in the United States in 2004 was estimated to be $1.9 trillion.6 If digestive disease costs were assumed to account for just 10% of all health care spending, the resulting estimate of direct costs would have been about twice our estimate.

GI Endoscopy Through diagnosis and management, endoscopy has a role in nearly all GI diseases as well as a crucial role in clinical research. It is estimated that ⬎20 million upper and lower GI endoscopies are performed yearly in the United States.7 There is no single national endoscopic database that can provide accurate, population-based information on the absolute number of GI endoscopies and their indications and diagnostic outcomes. To remedy this important gap in knowledge on the burden of GI 381

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Figure 3. All digestive cancers: age-adjusted incidence rates and 5-year survival rates, 1979 – 2004. (Source: Surveillance, Epidemiology, and End Results Program.)

disease, data were obtained for the period 2001–2005 from the Clinical Outcomes Research Initiative’s National Endoscopic Database (NED). Pediatric procedures are not represented, and the participating sites are overrepresented by veteran and military facilities. Nevertheless, the patterns of endoscopy in NED have been shown to be quite similar to that of a national sample of the Medicare population and may well be applicable to the United States as a whole.8 There is no independent confirmation of the indications and diagnoses reported by the endoscopist on the endoscopy record, although the report is frequently included in the medical record and used for billing.

Esophagogastroduodenoscopy Of the 885,593 upper and lower endoscopic procedures performed during 2001–2005, 30.6% were esophagogastroduodenoscopies (EGDs). The peak age for EGD was 50 –59 years, and 81.3% were performed on non-Hispanic whites, 7.3% on non-Hispanic blacks, and 8.0% on Hispanics. Excluding Veterans Affairs facilities, the majority of procedures were performed on women (57.2%). Of the 101 sites providing data to NED during 2001–2005, 36 did so throughout the 5-year period. At these “stable” sites, EGD increased by 20.3%, with use increasing across all age groups. Indications and findings were available from 77 practices (101 sites) that performed 270,957 EGDs from 2001 to 2005 (Table 6). Categories of indications and findings were not mutually exclusive and included groupings of symptoms, notably alarm symptoms (weight loss, vomiting, or bleeding) and bleeding (anemia, iron deficiency, melena, hematemesis, hematochezia, positive fecal occult blood test, or suspected upper GI bleed). The most common diagnostic abnormalities were mucosal abnormality, hiatal hernia, esophageal inflammation, stricture/ stenosis, and Barrett’s esophagus, each of which is char382

acteristic of, or a complication of, GERD. Combining these diagnoses, it can be inferred that the large majority of abnormal findings on EGD are associated with GERD.

All Digestive Cancers The Surveillance, Epidemiology, and End Results (SEER) program provides considerable information on cancer burden not available for other digestive diseases. SEER statistics used in this report are number of cases and incidence in 2004, and the time trends for incidence and 5-year survival following diagnosis between 1979 and 2004. In 2004, approximately 233,000 people were diagnosed with digestive system cancers, which represented 18% of all cancers and were second only to genital system cancers for the most commonly affected organ system. Two thirds of digestive system cancers occurred among people age ⱖ65 years. The median age of diagnosis was 70 years, compared with 67 years for all cancers.9 Ageadjusted rates were highest among non-Hispanic blacks and lowest among American Indians. Males had slightly higher rates than females. Age-adjusted incidence declined by 13.2% between 1979 and 2004, with the entire decline coming after 1986 (Figure 3). Survival was calculated as absolute survival, whereas other reports calculate survival relative to the general population with the same age and gender distribution, which results in higher apparent survival. The same trends, however, would be seen for either approach. Five-year survival increased an absolute 6% to 34.6%; thus, for every 100 people diagnosed with a digestive system cancer in 1999, 6 more survived ⱖ5 years than did those diagnosed 20 years earlier. There were approximately 3.5 million ambulatory care visits for first-listed digestive system cancer in 2004 and 4.2 million all-listed visits. The elderly, whites, and males had the highest rates of ambulatory care visits. Among all hospital discharges with digestive system cancers, about

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Figure 4. All digestive cancers: age-adjusted rates of ambulatory care visits and hospital discharges with all-listed diagnoses in the United States, 1979 – 2004. (Source: National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey [averages 1992– 1993, 1994 –1996, 1997–1999, 2000 –2002, 2003–2005], and National Hospital Discharge Survey.)

half were first listed. The main demographic difference between ambulatory care diagnoses and hospital diagnoses was that blacks had a higher age-adjusted rate of hospital diagnoses. Rates of ambulatory care visits for digestive system cancers did not change appreciably over the period 1992–2004, but hospitalizations rates declined by 13.6% over that period (Figure 4). In 2004, approximately 135,000 deaths were caused by digestive system cancers, which represented 24% of all cancers, second only to respiratory system as the most common organ system affected by cancer death. As underlying cause, digestive system cancers constituted 57.2% of all digestive disease deaths. Death rates among people ⱖ65 years were 5 times that of those aged 45– 64 years. Age-adjusted death rates were higher among blacks and men. There were 945,000 YPLL to digestive system cancer, the large majority occurring among males. Death rates from digestive system cancer declined steadily between 1979 and 2004 by an overall 19.8% (Figure 5), largely driven by a decline in colorectal cancer mortality.

Upper GI Diseases GERD In 2004, GERD was by far the most frequently first-listed digestive system condition at ambulatory care

visits, constituting 17.5% of all digestive system diagnoses. There were ⱖ6 outpatient visits with a GERD diagnosis listed per 100 people in the United States (Table 7). GERD was a common diagnosis in all age groups, although the highest rate was for those age ⱖ65 years. Age-adjusted ambulatory care visit rates were higher among blacks than whites, but were similar for females and males. GERD was the most common digestive system disease noted at hospital discharge, present on 23.5% of hospitalizations at which a digestive system condition was listed at discharge. The patterns by race and gender of rates of hospitalization with a diagnosis of GERD were similar to that of ambulatory care visits. About half of all hospital diagnoses were recorded at age ⱖ65 years. Rates of both all-listed ambulatory care visits and hospital discharges increased several-fold from the early 1990s to 2004 (Figure 6). Among other digestive system diseases, only HCV had a similar increase in medical care, but much of that increase was because hepatitis C was not recognized as a disease with its own ICD code until 1992. The increases in medical care for GERD began at least as early as the mid-1970s.10 Between 1975 and 2004, the rate of all-listed ambulatory care visits for GERD increased approximately 2,000%. It was in the mid-1970s that better means to diagnose (flexible endoscopes) and treat (histamine-2 receptor

Figure 5. All digestive cancers: age-adjusted rates of death in the United States, 1979 –2004. (Source: Vital Statistics of the United States.) 383

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Table 7. GERD: Number and Age-Adjusted Rates of Ambulatory Care Visits and Hospital Discharges With First-Listed and AllListed Diagnoses by Age, Race, and Gender in the United States, 2004 Ambulatory care visits First-listed diagnosis

Demographic characteristics Age (yrs) ⬍15 15–44 45–64 ⱖ65 Race White Black Gender Female Male Total

Number in thousands

Rate per 100,000

693 2083 2463 1611

1139 1656 3484 4433

5567 1028 3388 3462 6849

Hospital discharges

All-listed diagnoses Number in thousands

First-listed diagnosis

All-listed diagnoses

Rate per 100,000

Number in thousands

Rate per 100,000

Number in thousands

Rate per 100,000

1504 4064 6961 5813

2473 3230 9847 15,999

20 28 53 58

33 22 75 159

110 463 1050 1565

182 368 1486 4307

2267 2872

14,964 2603

6002 8075

122 21

49 65

2513 342

987 1107

2209 2462 2332

10,624 7718 18,342

6733 5506 6246

87 71 158

54 51 54

1936 1252 3189

1183 937 1086

Sources: National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (3-year average, 2003–2005), and Healthcare Cost and Utilization Project Nationwide Inpatient Sample.

blockers) became available, both of which stimulated recognition of the condition. Nevertheless, it is unlikely that all the increases in GERD-related statistics can be attributed solely to increased recognition. The proportion of hospitalizations for GERD represented by complications of ulcer, strictures, and stenosis changed little from 1983 to 1987 when they constituted 12.5% of first-listed hospitalizations for GERD to 2004 when they constituted 11.5% of first-listed hospitalizations.10 More than 60 million prescriptions for the treatment of GERD were estimated to have been filled at retail pharmacies in 2004, representing 48% of all prescriptions for digestive system disorders and ⬎50% of their cost. The large majority of prescriptions and their cost were for proton pump inhibitors, which were the 5 most commonly prescribed and costliest medications. Because over-the-counter medications were not included in this tabulation, the total medication cost may have been considerably higher.

Cancer of the Esophagus The 2 forms of esophageal cancer are squamous cell carcinoma, which occurs in the upper two thirds of the esophagus, and adenocarcinoma, which occurs in the lower third. Because the epidemiology of the 2 cancers is quite different, the SEER results are presented separately. Other national data sources do not differentiate as well, and those data therefore were combined. There are a number of contrasts in the occurrence of squamous and adenocarcinomas of the esophagus, including age and ethnic differences, but the most striking has been the trends in incidence. The incidence of squamous cell carcinoma declined over 25 years to 2004, when it was about half the rate of 1979 (Figure 7). In contrast, the incidence of esophageal adenocarcinoma rose approximately 5-fold between 1979 and 2004, more rapidly than any other common malignancy. Non-Hispanic whites and males

Figure 6. GERD: age-adjusted rates of ambulatory care visits and hospital discharges with alllisted diagnoses in the United States, 1979–2004. (Source: National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey [averages 1992–1993, 1994–1996, 1997–1999, 2000–2002, 2003– 2005], and National Hospital Discharge Survey.) 384

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Figure 7. Esophageal squamous cell cancer and esophageal adenocarcinoma: age-adjusted incidence rates, 1979–2004. (Source: Surveillance, Epidemiology, and End Results Program.)

had by far the highest risk of adenocarcinoma of the esophagus—a race and gender difference greater than for any other common digestive tract cancer. Esophageal cancer of either cell type was a frequent cause of cancer death, ranking third in 2004 among digestive system cancers (after colorectal and pancreatic cancer) and was responsible for ⬎13,000 deaths and 113,000 YPLL before age 75 years. Cancers of the gastroesophageal junction and cardia accounted for 4.6% of these deaths (see Cancer of the Stomach). Death rates increased between 1979 and 2004, but not during the last 6 years of that period.

Peptic Ulcer Disease In 2004, there were about 700,000 ambulatory care visits with peptic ulcer as the first-listed diagnosis and an equal number in which it was a secondary diagnosis. Ambulatory care rates increased with increasing age, were higher for blacks than for whites, and were higher among women. When listed at hospital discharge, peptic ulcer was the first-listed diagnosis 37% of the time. The frequency of outpatient and inpatient care declined for peptic ulcer disease (Figure 8), which continued a pattern that began in the 1970s, if not before.11 In the 12

years before 2005, age-adjusted ambulatory care visit rates with a peptic ulcer diagnosis declined 68%, and in the prior 25 years, hospital discharge rates declined 51%. Peptic ulcer was coded as the underlying cause among 3,692 deaths in 2004 and other cause among an additional 4,604 deaths. Nearly 80% of these deaths occurred among people age ⱖ65 years. Age-adjusted death rates were similar for blacks and whites, but were higher for males than females. Between 1979 and 2004 and parallel to the decline in medical care usage, mortality from peptic ulcer as underlying cause declined 62.6% and as underlying or other cause by 68.8%. This continued nearly a century of decline in peptic ulcer mortality.11

Cancer of the Stomach SEER includes cancers of the gastroesophageal junction and gastric cardia with gastric cancer. From 1979 to 2004, the incidence of cancers of the gastroesophageal junction and cardia approximately doubled, resulting in an increase in the proportion of gastric cancer at these sites from 14.9% in 1979 to 30.4% in 2004. However, for medical care and vital statistics, these sites were included with esophageal cancer.

Figure 8. Peptic ulcer disease: age-adjusted rates of ambulatory care visits and hospital discharges with all-listed diagnoses in the United States, 1979 –2004. (Source: National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey [averages 1992–1993, 1994 –1996, 1997– 1999, 2000 –2002, 2003–2005], and National Hospital Discharge Survey.) 385

Mini-Reviews and Perspectives continued

Figure 9. Gastric cancer: ageadjusted incidence rates (left axis) and 5-year survival rates (right axis), 1979 –2004. (Source: Surveillance, Epidemiology, and End Results Program.)

In 2004, the stomach was the third most common anatomical site for digestive system cancer, after the colon/ rectum and the pancreas. Cancer of the stomach had an older age distribution than did other GI cancers, with 68% of cases occurring at age ⱖ65 years. The median age of diagnosis was 71 years.9 Asians and Hispanics had the highest age-adjusted incidence rates; non-Hispanic whites had the lowest rate. The incidence of gastric cancer, as reflected by mortality rates, has been declining for ⬎70 years in the United States. Between 1979 and 2004, the incidence declined more than one third (Figure 9), although more in younger than older age groups. During that period, 5-year survival following diagnosis increased by almost 50%. Because gastric cancer now has somewhat better survival than other digestive system cancers, it was only the 4th leading cause of death among these cancers. Seventy percent of deaths with gastric cancer as the underlying cause occurred at age ⱖ65 years. Age-adjusted mortality rates were more than twice as high among blacks as whites and nearly twice as high among men as women. If cancer of the gastroesophageal junction were included among gastric cancer, the number of deaths would have increased 5.6% to 11,883 in 2004. Reflecting the declining incidence rate and longer survival, the age-adjusted mortality rate of gastric cancer fell by 49% between 1979 and 2004, the most rapid decline for any major digestive system cancer. References 1. Burden of digestive diseases in the United States. Washington, DC: US Government Printing Office, 2008; NIH publication no. 09-6443, pp 1–182. 2. Everhart JE. Overview. In: Everhart JE, ed. Digestive diseases in the United States: epidemiology and impact. Washington, DC: US Government Printing Office; NIH publication no. 94-1447, 1994:1–50. 3. Hodgson TA. The state of the art of cost-of-illness estimates. Adv Health Econ Health Serv Res 1983;4:129 –164. 4. Brown DM, Everhart JE. Cost of digestive diseases in the United States. In: Everhart JE, ed. Digestive diseases in the United States: epidemiology and impact. Washington, DC: US Government Printing Office; NIH publication no. 94-1447, 1994:55– 82.

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5. Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States. Gastroenterology 2002;122:1500 –1511. 6. Smith C, Cowan C, Heffler S, et al. National health spending in 2004: recent slowdown led by prescription drug spending. Health Aff (Millwood) 2006;25:186 –196. 7. Seeff LC, Richards TB, Shapiro JA, et al. How many endoscopies are performed for colorectal cancer screening? Results from CDC’s survey of endoscopic capacity. Gastroenterology 2004; 127:1670 –1677. 8. Sonnenberg A, Amorosi SL, Lacey MJ, et al. Patterns of endoscopy in the United States: analysis of data from the Centers for Medicare and Medicaid Services and the National Endoscopic Database. Gastrointest Endosc 2008;67:489 – 496. 9. National Cancer Institute. SEER cancer statistics review 1975– 200. Available: http://seer.cancer.gov/csr/1975_2005/results_ merged/topic_med_age.pdf. 10. Sonnenberg A. Esophageal diseases. In: Everhart JE, ed. Digestive diseases in the United States: epidemiology and impact. Washington, DC: US Government Printing Office; NIH publication no. 94-1447, 2004:299 –355. 11. Sonnenberg A. Peptic ulcer. In: Everhart JE, ed. Digestive diseases in the United States: epidemiology and impact. Washington, DC: US Government Printing Office; NIH publication no. 94-1447, 1994:357– 408.

Address requests for reprints to: James E. Everhart, MD, MPH, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, 2 Democracy Plaza, Room 655, 6707 Democracy Boulevard, MSC 5450, Bethesda, MD 20892-5450. e-mail: [email protected]; fax: 301-480-8300. The authors thank Danita Byrd-Holt, Bryan Sayer, Sanee Maphungphong, Beny Wu, Laura Fang, Laura Spofford, Polly Gilbert, Julie Kale, and Katherine Merrell of Social & Scientific Systems, Inc., for programming and production of tables and figures, Douglas Brown and Daniel Westbrook of Georgetown University for analysis and consultation on the cost of digestive diseases; David Lieberman and Nora Mattek of the Clinical Outcomes Research Initiative (CORI) for the national endoscopy data; Dedun Ingram at the National Center for Health Statistics for advice on age-adjustment; and Robert Kloos at Ohio State University for advice on recovery times from surgery. The authors disclose the following: Supported by HHS contracts N267200612918C and N267200700001G. The authors disclose no conflicts.