Rare clinically significant hepatic events and hepatitis B reactivation occur more frequently following rather than during direct-acting antiviral therapy for chronic hepatitis C: Data from a national US cohort.

Recently, cases of hepatitis B virus reactivation (HBVr) with direct-acting antiviral therapy (DAAs) for HCV have been reported. However, few data exist from large, Western cohorts. The study objectives were to evaluate the incidence of alanine aminotransferase (ALT) flares, clinically significant hepatic events, and HBVr among a national cohort of US veterans with prior exposure to HBV (anti-HBc+) treated with DAAs. We used a national administrative database to identify patients treated with DAAs from January 2014 through November 2016 and obtained clinical and demographic as well as HBV and HCV treatment data. HBVr was defined as an at least 1-log increase in HBV DNA titre. Among 17 779 anti-HBc+ patients, 17 400 were HIV- and 379 were HIV+. Among the HIV- patients, 17 266 (99%) were HBsAg- prior to DAA therapy and 134 were HBsAg+. Among HIV-, HBsAg- patients, ALT elevations greater than 10 times the upper limit of normal (ULN; ≥300 IU/mL) were rare and occurred more frequently after treatment completion: 31 cases (<0.1%) during vs 85 (0.6%) following treatment. Clinically significant hepatic events defined as ALT increases >100 IU/L with total bilirubin >2.5 mg/dL occurred in 39 cases (0.3%), most often following DAA completion (n = 35 cases, 3/35 in setting of HCV relapse). Among 31 patients with post-DAA hepatic events without HCV relapse, 10 (32%) were confirmed unrelated to HBVr by HBsAg and/or HBV DNA testing, 1 (3%) confirmed due to HBVr, and 20 (65%) did not have documented HBV-related testing. One additional case of HBsAg- to + seroreversion was identified. Among HBsAg+ DAA recipients, 2/97 (2%), both with cirrhosis, experienced ALT elevations ≥300 IU/mL in the setting of HBVr. In conclusion, clinically significant hepatic events and HBVr were rare and much more likely among HBsAg-positive individuals. Anti-HBc + patients should be monitored for ALT flares and HBVr during and possibly for up to 6 months post-DAA therapy.

Sustained Posttransplantation Diabetes Is Associated With Long-Term Major Cardiovascular Events Following Liver Transplantation.

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.

Successful Treatment of Hepatitis C in Renal Transplant Recipients With Direct-Acting Antiviral Agents.

The direct-acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end-stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon-free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy-proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon-based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment-related side effects.

An Assessment of HIV-Infected Patients Dying in Care for Deceased Organ Donation in a United States Urban Center.

Organ transplantation is an acceptable option for human immunodeficiency virus (HIV)-infected patients with end-stage kidney or liver disease. With worse outcomes on the waitlist, HIV-infected patients may actually be disproportionately affected by the organ shortage in the United States. One potential solution is the use of HIV-infected deceased donors (HIVDD), recently legalized by the HIV Organ Policy Equity (HOPE) Act. This is the first analysis of patient-specific data from potential HIVDD, retrospectively examining charts of HIV-infected patients dying in care at six HIV clinics in Philadelphia, Pennsylvania from January 1, 2009 to June 30, 2014. Our data suggest that there are four to five potential HIVDD dying in Philadelphia annually who might yield two to three kidneys and three to five livers for transplant. Extrapolated nationally, this would approximate 356 potential HIVDD yielding 192 kidneys and 247 livers annually. However, several donor risk indices raise concerns about the quality of kidneys that could be recovered from HIVDD as a result of older donor age and comorbidities. On the other hand, livers from these potential HIVDD are of similar quality to HIV-negative donors dying locally, although there is a high prevalence of positive hepatitis C antibody.

Adherence to the 2011 American Gastroenterological Association medical position statement for the diagnosis and management of Barrett's esophagus.

Considerable variability exists in adherence to practice guidelines for Barrett's esophagus (BE). Rapid advances in management approaches to BE led to a new American Gastroenterological Association (AGA) medical position statement in 2011. Our aim was to assess how well members of the AGA Clinical Practice section adhered to these guidelines. A self-administered survey incorporating questions on diagnostic criteria, cancer risk estimates, screening, surveillance, and therapeutics for BE was distributed electronically to 5850 North American members of the AGA Clinical Practice section. The response rate was 470 of 2040 opened e-mails (23%). Intestinal metaplasia was required for diagnosis of BE by 90%, but the Prague classification was used by only 53% of those aware of it. The annual risk of progression to esophageal adenocarcinoma was reported as 0.1-0.5% by 76%. Screening practices were variable, with 35% screening all patients with chronic gastroesophageal reflux disease and 15% repeating endoscopy in patients with gastroesophageal reflux disease following a negative screening. Surveillance guidelines were followed by 79% for nondysplastic BE and 86% for low-grade dysplasia, with expert pathology confirmation of dysplasia reported by 86%. Proton pump inhibitor dosing was variable, with 18% administering twice-daily doses and 30% titrating dose to symptoms. Ablation therapy was recommended by 6% for nondysplastic BE, 38% for low-grade dysplasia, and 52% for high-grade dysplasia. There is satisfactory adherence to the new AGA guidelines with respect to diagnosis, cancer risk estimates, and surveillance intervals in a select group of respondents. However, adherence continues to be variable in the use of the Prague classification, screening, and dosing of antisecretory therapy. Use of ablation therapy increases with grade of dysplasia. The reason for continued variability in adherence to BE practice guidelines remains unclear, and more evidence-based guidance is required to enhance clinical practice.

Waiting time and explant pathology in transplant recipients with hepatocellular carcinoma: a novel study using national data.

Risk factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation have been well described. It has been surmised that longer time on the waitlist may select for tumors with a lower-risk of recurrence posttransplant, as patients with unfavorable tumor characteristics would be delisted due to tumor progression. Utilizing national explant pathology records from transplant recipients waitlisted with T2 HCC exception points, this study explored the correlation between waiting time and the development of pathologic HCC features associated with increased risk of tumor recurrence. Of 1976 explant pathology reports submitted nationally between April 8, 2012 and June 30, 2013, 1453 (73.5%) were from recipients with automatic T2 HCC exception points. There was no association between pretransplant waiting time and the proportion of HCC explants with either: (i) a poorly differentiated tumor; (ii) macrovascular invasion; (iii) HCC beyond Milan or University of California San Francisco criteria; (iv) HCC beyond the "up-to-seven" criteria; or (v) extra-hepatic or lymph node involvement. Though there was a statistically significant increase in microvascular invasion in recipients with pretransplant waiting 6-12 months, this association was not seen when adjusted for United Network for Organ Sharing region. These findings suggest that waiting time alone may not select for tumors with more favorable characteristics.

Risk of myocardial infarction associated with chronic hepatitis C virus infection: a population-based cohort study.

Hepatitis C virus (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis. However, it remains unclear if HCV infection increases the risk of acute myocardial infarction (MI). To determine whether HCV infection is an independent risk factor for acute MI among adults followed in general practices in the United Kingdom (UK), a retrospective cohort study was conducted in The Health Improvement Network, from 1996 through 2008. Patients ≥18 years of age with at least 6 months of follow-up and without a prior history of MI were eligible for study inclusion. HCV-infected individuals, identified with previously validated HCV diagnostic codes (n = 4809), were matched on age, sex and practice with up to 15 randomly selected patients without HCV (n = 71 668). Rates of incident MI among patients with and without a diagnosis of HCV infection were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards regression, controlling for established cardiovascular risk factors. During a median follow-up of 3.2 years, there was no difference in the incidence rates of MI between HCV-infected and -uninfected patients (1.02 vs 0.92 events per 1000 person-years; P = 0.7). HCV infection was not associated with an increased risk of incident MI (adjusted HR, 1.10; 95% confidence interval [CI], 0.67-1.83). Sensitivity analyses including the exploration of a composite outcome of acute MI and coronary interventions yielded similar results (adjusted HR, 1.16; 95% CI, 0.77-1.74). In conclusion, HCV infection was not associated with an increased risk of incident MI.

Abdominal wall dimensions and umbilical position vary widely with BMI and should be taken into account when choosing port locations.

BACKGROUND: Many surgeons rely on the umbilicus when determining the location of ports for laparoscopic procedures and falsely assume that it is located in the vertical midline. The purpose of this study was to assess the degree of variation in umbilical position and abdominal dimensions in the general population. METHODS: Torso length, abdominal girth, weight, and height were recorded for 259 patients over a 9-month period. Body mass index (BMI) was calculated and used to classify patients into four groups: underweight, normal, overweight, and obese. RESULTS: Average umbilical position for all BMI groups was below the true vertical midpoint and dropped further caudally as BMI increased. In addition, average abdominal dimensions increased with increasing BMI. There was no statistical difference between males and females in each BMI group regarding umbilical position or abdominal dimensions. CONCLUSION: There is a clear relationship between increasing BMI and a drop in umbilical position as well as an increase in abdominal dimensions. We recommend determining umbilical position and abdominal dimensions prior to placing ports and shifting port positions toward target quadrants.

The role of the surgeon in the evolution of flexible endoscopy.

Several cultures, including the Egyptians, Greeks, Romans, and Arabs, made attempts to view accessible human body cavities using a variety of instruments such as spatulas and specula. The first endoscope was created in 1806 when Phillip Bozzini, a German-born urologist, constructed the lichtleiter, which used concave mirrors to reflect candlelight through an open tube into the esophagus, bladder, or rectum. Maximilian Carl-Friedrich Nitze, another German urologist, produced the first usable cystoscope in 1877 by using series of lenses to increase magnification. He was also the first to place light inside the organ of interest to aid visualization. In 1880 Mikulicz made the first gastroscope using a system similar to Nitze's cystoscope. Modern endoscopy was born with the introduction of the fiberoptic endoscope in the late 1950s. Over the ensuing 50 years endoscopy revolutionized many aspects of the surgeon's practice. Endoscopy can now be used to diagnose and often treat gastrointestinal cancer, hemorrhage, obstruction, and inflammatory conditions. This review was initiated by the SAGES Flexible Endoscopy Committee to chronicle the role of the surgeon in the development and introduction of flexible endoscopy into clinical practice, historically and in contemporary surgery. Flexible endoscopy evolved out of surgeons' need to overcome diagnostic and therapeutic challenges. There have been many recent technological advances that facilitate endoluminal therapies, and flexible endoscopy is now traversing new ground. Surgeons have been major contributors in the development of all aspects of endoscopy. There is a continually expanding list of therapeutic options available to patients. The difficult questions of which procedure, on which patient, and when can be answered best by the surgeon versed in endoscopic, laparoscopic, and open surgical techniques.

Colonoscopic screening for colon cancer.

Colonoscopic screening for colon cancer was suggested in 1988 [17], but it has only recently received significant acceptance. It is a topic of much current discussion among both health care providers and the general public, especially since the nationally broadcasted colonoscopy of a well-known television anchor person [8]. This brief discussion presents the role of colonoscopy in colon cancer screening. It sets forth the rationale for endoscopic screening, evaluates it using World Health Organization guidelines, and briefly considers the timing and termination of screening. By screening is meant the testing of asymptomatic individuals in a large population. This is to be distinguished from surveillance, which involves ongoing follow-up testing of individuals at known risk. The former is the subject of this discussion.

Altered plasma matrix metalloproteinase-9/tissue inhibitor of matrix [corrected] metalloproteinase-1 concentration during the early postoperative period in patients with colorectal cancer.

BACKGROUND: The authors have previously demonstrated that insulin-like growth factor binding protein-3 (IGFBP-3) is depleted in plasma for 1 to 3 days after major open surgery (OS), but not after laparoscopic surgery (LS). After surgery, IGFP-3 cleavage occurs rapidly and is likely attributable to altered plasma proteolytic activity. This study aimed to assess plasma proteolysis after both open and closed colorectal resection and, if possible, to identify a protease/protease inhibitor system affected by surgery. METHODS: Plasma from 88 patients with colorectal cancer (stages I-III) who underwent resection was obtained preoperatively (pre-OP) and on postoperative days (POD) 1 to 3. Plasma proteolytic activity was assessed via zymography. On the basis of the results, specific protease and protease inhibitor concentrations were next measured via enzyme-linked immunoassay (ELISA). Statistical analysis was performed using Wilcoxon's test. RESULTS: Early after surgery, zymography showed a predominant band representing a 92-kDa gelatinase corresponding to a proform of matrix metalloproteinase-9 (MMP-9), a protease known to cleave IGFBP-3. In OS patients, the mean concentration of plasma MMP-9 was significantly higher on POD 1 than at pre-OP (p < 0.003). On POD 2 and 3, no differences were noted. In the LS group, the mean levels of MMP-9 before and after surgery were comparable. The levels of a natural MMP-9 inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), also were measured. In the OS group, the level of TIMP-1 was significantly higher on POD 1 (p < 0.0003) and POD 2 (p < 0.01) and 3 (p < 0.01) than at pre-OP. In the LS group, a smaller but significant increase in TIMP-1 levels was found between the pre-OP sample and the POD 1 (p < 0.01) and POD 2 (p < 0.01) samples. No difference was noted on POD 3 (p = 0.1). CONCLUSIONS: Open surgery, but not laparoscopic surgery, is accompanied by a short-lived significant increase in MMP-9 levels, which likely accounts for the decrease in IGFBP-3 levels observed after OS. The transitory nature of MMP-9 imbalance may be attributable to the increase in TIMP-1 levels postoperatively.

A preliminary prospective study of the usefulness of a magnetic endoscope locating device during colonoscopy.

BACKGROUND: Although magnetic endoscope imaging of the colonoscope via the Endoscope Positioning Detecting Unit (EPDU) has been studied to some extent in Europe, its application in the United States has been limited. The purposes of this study were to determine whether the technique enabled for accurate localization of the lesion and to determine if and how the device facilitated scope insertion and completion of the colonoscopic exam. METHODS: Outpatient colonoscopies using the EPDU were performed by three experienced surgical endoscopists over a 5-month period. A specialized scope with electromagnetic coils or a regular scope with a magnetic probe insert in the instrument channel was used for the duration of the examination to identify loops and localize pathology. RESULTS: A total of 80 colonoscopies were performed with the device. In two patients, the probe insert was removed prior to completion of the procedure; thus, the total number of examinations included in the study was 78. The EPDU was used in conjunction with transillumination to estimate the location of polyps or cancers in the 33 patients (42%) in whom such lesions were found. In the four patients who subsequently underwent operation, the lesion's location as estimated by EPDU was verified. In regard to the usefulness of the device during insertion, the EPDU led to the discovery of loops and to the application of pressure that resulted in prompt completion of the examination in 28% of cases (deemed most useful). In 33% of cases, the device identified loops and led to the application of abdominal wall pressure and early position changes, thus facilitating the examination; however it did not lead to its immediate or rapid completion. In 39% of cases, the device was not required or used for insertion due to the simple nature of the examination. CONCLUSIONS: The EPDU was accurate in estimating lesion location. The device also holds promise as an aid in the completion of difficult exams (about 30% of cases in this study).

Open surgery induces a dramatic decrease in circulating intact IGFBP-3 in patients with colorectal cancer not seen with laparoscopic surgery.

BACKGROUND: As shown earlier by the authors via Western blot analysis, open (OS) but not laparoscopic surgery (LS) induces a qualitative decrease in plasma insulin-like growth factor-binding protein 3 (IGFBP-3) levels on postoperative day 1 (POD 1). Intact IGFBP-3 has tumor suppressive effects, but its degradation products do not. Enzyme linked immunoassay (ELISA) inevitably measures both. In this study, using a novel combined Western blot and ELISA analysis method, precise plasma levels of intact IGFBP-3 on POD2 after open and closed colorectal cancer resection (stage I-III) were determined. METHODS: This study included 15 OS patients with a mean incision length of 26.7 +/- 15.5 cm and 16 LS patients with a mean incision length of 5.3 +/- 3.1 cm. Intact IGFBP-3 levels were determined via ELISA and Western blot analysis in plasma collected preoperatively and postoperatively. RESULTS: In the OS patients, the mean preoperative concentration of intact 43-45 kDa IGFBP-3 protein was 1920 +/- 1430 ng/ml. It decreased dramatically on POD2 to 355 +/- 545 ng/ml (p < 0.005). In the LS group, no significant difference was noted between the preoperative level (1305 +/- 807 ng/ml) and the POD2 level (922 + 714 ng/ml). CONCLUSIONS: Open cancer resection, unlike its minimally invasive alternative, induces a dramatic decrease in concentration of intact IGFBP-3, which may have important implications with regard to colon cancer recurrence.

Small bowel neoplasia in coeliac disease.

There is an increased risk of small bowel adenocarcinoma in patients with coeliac disease compared with the normal population. It has been suggested that adenocarcinoma of the small intestine in coeliac disease arises through an adenoma-carcinoma sequence but there has been only one reported case of a small bowel adenoma in a patient with coeliac disease. We report three additional cases of a small bowel adenoma in the setting of coeliac disease. In addition, four cases of small bowel adenocarcinoma are also reported, one of which was found adjacent to a jejunal villous adenoma. These cases emphasise the risk of the development of small bowel neoplasia for patients with coeliac disease and support the concept that small bowel adenocarcinoma in coeliac disease arises from adenomas.

Surgical implications of colonoscopy.

Colonoscopy, although increasingly used as a screening tool, has many surgical applications. As a tool for the abdominal surgeon, colonoscopy may be used not only to diagnose neoplasia, but also hemorrhage, and inflammatory and obstructive disorders. Therapeutically, endoscopic polypectomy has impacted the incidence of colorectal cancer, and further visualization techniques have augmented the ability of the endoscopist to discriminate between benign and neoplastic lesions. Colonoscopy remains a necessary implement to facilitate the diagnosis and therapy of those patients with disorders of the colon and rectum.

The percentage of CD31+ T cells decreases after open but not laparoscopic surgery.

BACKGROUND: Efficient killing of tumor cells depends on T cells that migrate from the circulation to the peripheral tissues; these cells express CD31. This study was undertaken to determine the impact of open (OS) and laparoscopic (LS) colorectal surgery on the percentage of circulating CD3+CD31+ cells. METHODS: Peripheral blood was collected from 27 OS and 24 LS colon cancer patients preoperatively (preOP) and on postoperative days 1 (POD1) and 3 (POD3). CD31+ T cells were assessed by flow cytometry using monoclonal antibodies. RESULTS: In the OS group, the percentage of CD3+CD31+ cells was significantly lower in POD1 and POD3 samples compared to the preOP results. LS surgery did not result in a significant change in the percentage of these T cells. A significant correlation was found between the decrease in the percentage of CD3+CD31+ cells and the length of incision in OS patients. CONCLUSIONS: The percentage of CD3+CD31+ cells decreases following OS but not LS and may be related to incision length. This may compromise T cell function in the peripheral tissues in the postoperative period.

Colonoscopy in mice.

INTRODUCTION: Current investigational models of murine colitis and colon cancer necessitate sacrifice of animals in order to obtain colonic tissue. The purpose of this study was to develop a safe method of murine colonoscopy that would allow serial evaluation and mucosal biopsies of the same animal. METHODS: Nine mice (two C3H, two C57/BL6, and five IL-10 deficient) were studied a total of four times each over 4 weeks. Three mice [APC (Min +/-)] were examined three times each. Mice were gavaged with 1 cc of a polyethylene glycol solution on the day prior to colonoscopy. Solid chow was withheld and the mice were maintained on Pedialyte. Mice were anesthetized with ketamine and xylazine. A flexible pediatric cystoscope (2.1-mm diameter) with a single biopsy channel was introduced per anum, and the colon was gently insufflated with air to a mean pressure of less than 5 mmHg. Saline irrigation was used when necessary. A single biopsy was obtained from the rectosigmoid colon during each examination. RESULTS: A total of 46 examinations were carried out. One mouse died after being anesthesized for the fourth examination, and two mice [one IL-10 knockout and one APC (Min+/-)] died one day after the 3rd examination. No other complications were noted. The average length of insertion was 3 cm. Transillumination allowed for localization of the endoscope tip. Biopsies, although quite small, were sufficient for pathologic evaluation and diagnosis. CONCLUSIONS: Murine colonoscopy is a safe and feasible technique. It permits consecutive visual and histopathological examinations, and it allows the investigator to monitor the response of the murine colon to experimental interventions.

Increased incidence of colorectal adenomas in follow-up evaluation of patients with newly diagnosed hyperplastic polyps.

BACKGROUND: Although adenomatous polyps have been established clearly as precursor lesions for most cases of colorectal cancer, the role, if any, of hyperplastic polyps remains uncertain. The aim of the current study was to determine whether a patient with an index finding of hyperplastic polyp on colonoscopy is at increased risk for adenomatous polyps. METHODS: We conducted a retrospective cohort study using the records of a single surgeon's colonoscopic experience over a 20-year period (June 1973 to December 1994). Patients found to have hyperplastic lesions on index colonoscopy were compared with those who had "clean" index colonoscopies. The two groups were compared for the subsequent diagnosis of adenomatous polyps on follow-up colonoscopies. Those with cancer or adenomas at index colonoscopy or in their history were excluded. We used Cox proportional hazard modeling with subsequent adenoma or cancer diagnosis at follow-up colonoscopy as the outcome, controlling for age and gender. RESULTS: We identified 42 patients for whom hyperplastic polyps were the only colorectal neoplasms found on the index examination, in contrast to 362 control patients who had a "clean" index examination. In this cohort study, patients found to have only hyperplastic polyps on initial examination had a rate of subsequent adenoma diagnoses (42%) twice that of patients with a clean initial colonoscopy (21%). Mean follow-up time was 4.3 years. The relative rate ratio was 2.0 (95% confidence interval, 1.2-3.4). CONCLUSIONS: This study suggests that patients found to have hyperplastic polyps on initial colonoscopic examination may have twice the risk of adenomas on follow-up colonoscopy, as compared with those who have clean initial examinations. If this finding is borne out in larger prospective studies, surveillance strategies may need to be modified accordingly.

Significance of unsuspected celiac disease detected at endoscopy.

BACKGROUND: Endoscopy provides an opportunity to diagnose unsuspected celiac disease. METHODS: We prospectively identified patients undergoing endoscopy for reasons other than the evaluation of diarrhea or suspected malabsorption, who had endoscopic signs in the duodenum suggestive of celiac disease and in whom villous atrophy was confirmed. Patients were assessed for nutritional deficiencies, reduced bone density, parameters of calcium metabolism, and malignancies. RESULTS: Nine patients (3 women and 6 men) were identified among 1749 patients undergoing endoscopy between January 1990 and May 1998, representing a rate of unsuspected celiac disease of 1 per 194 endoscopies. The duodenal abnormalities were as follows: reduced or absent folds in 6, scalloped folds in 5, mosaic appearance in 3, and mucosal fissures in 2. Assessment revealed iron deficiency in 5, folate deficiency in 1, osteopenia in 4, osteoporosis in 1, and hypocalciuria in 4. Three had malignancies associated with celiac disease, 2 esophageal squamous carcinomas, and 1 jejunal adenocarcinoma. CONCLUSIONS: Unsuspected celiac disease can be diagnosed at endoscopy by recognition of changes in the duodenum. When detected, patients have one or more manifestations of the disease. Celiac disease is more common in the United States than previously considered and endoscopy provides an opportunity to establish the diagnosis.