DDW Potpourri: Colonoscopy, CT, Popcorn, and More

By Bruce Sylvester

WASHINGTON, DC—The findings of several important studies presented this year at Digestive Disease Week are reported here, including why you should not deny colonoscopies to elderly patients, data on a promising new sedative for patients undergoing a colonoscopy, the appropriate use of computed tomography (CT) for presumed appendicitis, and the possible gastroprotective effects of popcorn.

Don't Deny Colonoscopy to the Elderly for Fear of Intolerability

Even though colonoscopy among older patients (>75 years) is statistically less successful in imaging the colon, procedures that are halted because of discomfort in the elderly are rare, and this possibility should not discourage its use.

"We found that it is poor bowel prep, not intolerance, that causes most failures in this group," Kinesh Patel, MD, gastroenterologist at Hammersmith Hospital, Imperial College of Medicine, London, told IMWR. "And it turns out, older patients who are often denied the procedure based on fears of intolerability show better tolerance than younger patients."

Data were analyzed from all colonoscopies performed at Hammersmith Hospital during 1981. Rates of complete examination were determined, as defined by cecal intubation, and reasons for failure in patients who were not fully imaged were noted.

Most patients had received 4 L of polyethylene glycol bowel preparation, unless specifically contraindicated.

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Among patients younger than 75 years, 11.8% had an incomplete colonic examination. The rate rose to 20.7% ( <.001) among those older than age 75.

The higher failure rate among the older patients was largely the result of poor bowel preparation, which was responsible for 42.5% of the unsuccessful examinations.

Only 0.7% of colonoscopies in the elderly were stopped because of discomfort/intolerance, while 2.6% of the procedures were stopped among younger patients.

Colonoscopy showing erythematous changes with congested mucosa.

Very Old Patients with Colon Cancer Deserve Optimal Therapy

Although very old patients (≥85 years) with colorectal cancer are more likely to die from it than younger patients, many of these older patients have a good relative life expectancy after surgery and thus should receive optimal therapy.

"Relative to other medical conditions, very elderly patients have a good survival rate from colorectal cancer, and they should not be excluded from optimal treatment because of age," coinvestigator Glen Doherty, MD, gastroenterologist at the Centre for Colorectal Disease, St. Vincent's University Hospital, Dublin, Ireland, told IMWR. "We found that age in years matters less in determining treatment; what really counts is life performance ability and tumor stage."

In this retrospective study, data were analyzed from 2237 patients; the majority of the patients (n = 2147) were under age 85; a minority (n = 90) were ≥85 years; all had colorectal cancer and were admitted to St. Vincent's University Hospital.

The older group included more women (66% vs 47%) and had more right-sided tumors. However, rates of surgery and resection were similar in both groups. None of the very old patients underwent chemotherapy.

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Early (30-day) mortality was significantly higher in the very old group (11% vs 4%; = .004), and their long-term cancer-related survival was significantly lower ( <.001). However, relative survival beyond the postoperative period in the very elderly was similar to that of their peers in the general population, with 50% of the elderly surviving at least 2 years postprocedure, Dr Doherty emphasized.

Analysis showed that tumor stage and surgical resection had highly significant effects on survival and that age ≥85 years at diagnosis had only a small, independent influence on outcomes.

"These results suggest that investigations to diagnose colorectal cancer and aggressive operative therapies are justified in very elderly patients," the investigators concluded.

Nonopioid Option Safe, Effective as Colonoscopy Sedative

Fospropofol (Aquavan; MGI Pharma), an investigational drug, is both safe and effective for colonoscopy sedation and could become an alternative to the use of opioid drugs for sedation, new data have shown.

"This phase 3 study allowed us to begin to compare fospropofol to regimens that we currently use for sedation in colonoscopy," coinvestigator Douglas Rex, MD, professor of medicine at Indiana University Medical Center in Indianapolis, told IMWR. "Currently, opioid drugs are widely used in combination with midazolam for sedation in this procedure. Fospropofol could become an opioid-sparing alternative, with no loss of efficacy."

Investigators randomized 312 adults who underwent colonoscopy to a 2:3:1 allocation ratio to receive an initial dose of fospropofol 2.0 mg/kg, fospropofol 6.5 mg/kg, or midazolam 0.02 mg/kg, respectively, after pretreatment with 50 μg of fentanyl (Sublimaze).

Patients were permitted to receive supplemental doses of the assigned sedative for each protocol. A total of 87% of patients who received an initial bolus dose of 6.5 mg/kg of fospropofol achieved sedation success compared with only 26% for fospropofol 2 mg/kg and 69% for midazolam. However, "the study was not powered to show differences between fospropofol disodium and midazolam," the investigators noted.

There were no drug-related serious adverse events or deaths during the study, and no patients required manual or mechanical ventilation.

Use Preoperative CT Scanning Selectively for Presumed Appendicitis

Because it can delay surgery and increase the risk of perforation, the use of preoperative CT scanning for patients with presumed appendicitis should be very selective.

"We found that CT scanning is used too often, causes unneeded delays in treatment, and thereby leads to unnecessary perforations," coinvestigator Herbert Chen, MD, assistant professor, Division of General Surgery, and chief of Endocrine Surgery at the University of Wisconsin School of Medicine, Madison, told IMWR.

CT scanning records were analyzed for adult appendicitis patients at the University of Wisconsin Hospital during a 3-year period. Surgical findings, including incidence of perforation, were correlated to imaging results.

Of the 410 patients undergoing appendectomy for presumed acute appendicitis, 255 (62%) underwent preoperative CT. The remaining 155 (38%) patients did not undergo CT imaging before surgery.

CT had a 93% overall sensitivity but only a 59% specificity for acute appendicitis. Patients who underwent CT scanning were older, and the majority were women. These patients waited longer between admission and surgery than those who were not scanned (8.2 vs 5.1 hours).

Notably, perforation appeared in 17% of those who were scanned and 8% of those who were not scanned.

"Since the delay entailed in the scanning correlated with higher perforation, we conclude that CT should be used more selectively," Dr Chen said.

New Biomarker May Replace Biopsy for Assessing NAFLD Progression

A blood test could replace liver biopsy as the standard means of determining when nonalcoholic fatty-liver disease (NAFLD) has progressed to nonalcoholic steatohepatitis (NASH), the most extreme form of nonalcoholic liver disease.

"We have an explosion of nonalcoholic fatty-liver disease among all age-groups in the United States, and we need to identify a noninvasive biomarker test for the dangerous progression to NASH," coinvestigator Ariel Feldstein, MD, assistant professor of pediatric gastroenterology at the Cleveland Clinic Foundation, Ohio, told IMWR. "We found evidence that strongly suggests that measuring CK-18 [cytokeratin 18] fragment levels in the blood could be that biomarker."

This ancillary study of the NASH National Institutes of Health Clinical Research Network included 178 patients with biopsy-proven NAFLD and 150 age-matched healthy controls.

Measurements of the blood-borne CK-18 fragments in patients with NAFLD ranged from 68 to 3000 U/L, which was significantly higher than the levels seen in the healthy control patients (average, 45 U/L).

For every 50-U/L increase in CK-18 fragments, the likelihood of qualifying for a definitive diagnosis of NASH increased by 74%.

Measuring CK-18 fragment levels can effectively differentiate NASH from simple steatosis in patients with NAFLD, the investigators said, adding that this finding supports the development of such a test for use in clinical practice.

Racial, Geographical Bias in Hepatocellular Cancer Therapy

A review of national cancer registry data reveals significant racial and regional bias in the use of surgical therapy for hepatocellular carcinoma.

"Race and geographic location have a significant impact on whether a patient will get optimal surgical treatment for this cancer," coinvestigator Christopher Sonnenday, MD, MHS, clinical lecturer and fellow, Department of Surgery, Division of Transplant Surgery, University of Michigan Health System, Ann Arbor, told IMWR.

Using data from the Surveillance, Epidemiology, and End Results (SEER) national cancer registry to determine patterns of surgical therapy, the investigators analyzed data for all patients with hepatocellular carcinoma submitted to the SEER 17 Public-Use database between 1998 and 2003.

They then correlated socioeconomic data from the 2000 US Census (for the county of residence of each patient) to the SEER data for 14,902 patients. Of these, 20% had undergone surgical therapy, 8.5% had resection, 6.1% had ablation, and 4.9% had a transplant.

Standard tools were used to measure the association between surgical therapy type (ie, ablation, hepatic resection, or transplantation) and patient demographics and tumor description. Results showed:

• Race and place of residence were significant determinants of the likelihood of surgery in patients with liver cancer
• Blacks were 25% less likely to receive surgical therapy than whites
• Asians were 27% more likely to undergo surgery than whites
• Gender also played a role; younger women who had a single, small tumor were most likely to be treated surgically
• Geographic differences in the operative treatment of hepatocellular carcinoma were reflected by rates that ranged from 8% in Georgia to 31% in Alaska and Hawaii
• Patients living in densely populated counties with higher rates of unemployment were less likely to be offered a surgical intervention.

"Since surgery is the only effective treatment for people with this disease, we need to get beyond these disparities in treatment in the United States," said Dr Sonnenday.

Nut, Corn, Popcorn Not Linked to Diverticulitis Complications

Consumption of nuts, corn, and popcorn does not increase the risk of complications associated with diverticulitis, as was previously thought. "In fact, we saw a link between frequent popcorn consumption in men and a reduced risk of developing diverticulitis," coinvestigator Lisa Strate, MD, assistant professor of gastroenterology at the University of Washington School of Medicine in Seattle, told IMWR.

The retrospective analysis included 47,454 American men (aged 40-75 years) from the Health Professionals Follow-up Study who were free of diverticular disease, gastrointestinal cancer, and inflammatory bowel disease at baseline (in 1986).

Men who reported newly diagnosed diverticulosis or diverticular complications on biennial follow-up questionnaires also received supplemental questionnaires to determine the details of their diagnosis and treatment.

Recent nut, corn, and popcorn consumption levels were ascertained every 4 years from a validated 131-item food frequency questionnaire.

Analyzing data from 18 years of follow-up, the investigators found 383 cases of diverticular bleeding and 801 cases of diverticulitis. Among men with diverticulitis, no positive association was found between the disease and consumption of nuts, corn, and popcorn, alone or combined.

After adjusting for risk factors for diverticular complications, men with the highest popcorn intake (at least 2 servings weekly) had a 28% decrease in the risk of diverticulitis compared with men with the lowest intake (<1 serving monthly). Similar negative associations were reported among the men with the highest intake of nuts and the highest combined intake of nuts, corn, and popcorn.

The investigators concluded, "Data from this large, prospective cohort indicate that nut and corn consumption do not increase the risk of diverticular complications. In fact, frequent popcorn consumption was associated with a reduced risk of diverticulitis."