RSNA: Two Needles Better than One in Ultrasound-Guided Aspiration for Tendinitis

By Peggy Peck , Executive Editor, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine.

CHICAGO, Nov. 28 -- Ultrasound-guided aspiration and lavage of shoulder calcifications using two 16-gauge needles provides durable functional improvement and relief from pain caused by tendinitis, researchers here reported.

In a case series of 2,788 patients treated over a 12-year period, patients achieved a 61% reduction in shoulder pain and improved function by 34.3% compared with baseline, said Luca M. Sconfienza, M.D., of Santa Corona Hospital and the University of Genoa in Genoa, Italy.

Action Points

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• Explain to interested patients that lavage/aspiration is a well-recognized therapy for tendinitis, but the procedure is typically done with a single needle.
• Note that this study was published as an abstract and presented at a conference. The data and conclusions should be considered to be preliminary until published in a peer-reviewed publication.

The use of two needles rather than one resulted in more complete aspiration of calcium from the shoulder because the aspiration is aided by "constant pressure from the saline infusion in the other needle," Dr. Sconfienza told attendees at the Radiological Society of North America meeting. "This is an in-and-out approach."

Moreover, despite the use of 16-gauge needles, "which are about one-third bigger than the needles used in single-needle lavage/aspiration, there were no tendon tears associated with the procedure," Dr. Sconfienza said.

Dr. Sconfienza and colleagues enrolled the patients, ages 29 to 73, beginning in 1994; 990 were men.

The procedure takes "about 10 minutes," said co-author Francesca Lacelli, M.D., and patients begin to feel relief 48 hours after the procedure.

Using this technique, all the calcium in the shoulder was removed in 70.1% of procedures. In 23.5%, the calcium was reduced by more than 50%.

Dr. Sconfienza said the procedure was also inexpensive -- he estimated the cost of therapy at $98 per procedure. But he said that all patients were referred for physical therapy, which would be an additional cost.

He said, too, that the procedure could also be used to aspirate calcium deposits from other joints -- knees and elbows for example. He estimated that 7% to 10% of the general population develops calcium in joints.

Philip O. Alderson, M.D., of Columbia University, who chairs the RSNA communications committee, said that, as a concept, lavage and aspiration is not new, but, he said, the two needle approach was novel.

Dr. Alderson said the procedure is likely to work best when the calcium is contained in a gelatinous matrix, but was probably not effective for removing hardened calcium.

Dr. Lacelli agreed with this observation, but, she added, "the pain of tendinitis usually subsides when calcium hardens," whereas patients with a "gelatinous matrix" are likely to experience significant pain.

"Our patients were all very symptomatic, which may explain why the procedure was so successful," she said.

Drs. Sconfienza, Lacelli, and Alderson said they received no research funding, honoraria, or consulting fees from imaging companies or the pharmaceutical industry. The study was investigator initiated and institutionally funded.

Primary source: Radiological Society of North America

Source reference:

Sconfienza LM, et al "Ultrasound (US)-guided percutaneous approach to the therapy of calcific tendinitis of rotator cuff" RSNA Meeting 2007; SST15-09.

Related Article(s):

Shoulder Tendinitis Responds to Lavage and Needle Aspiration

        

Gracias Dr. José Manuel Ferrer Guerra!!

Vitamin C May Be Effective Against Common Cold Primarily in Special Populations

News Author: Laurie Barclay, MD

CME Author: Penny Murata, MD

Vitamin C (ascorbic acid) may be effective against the common cold primarily in special populations, according to the results of a systematic Cochrane review published online in the July 18 issue of the Cochrane Database of Systematic Reviews. Most evidence suggests that an oral dose of 0.2 g or more of vitamin C is ineffective in treatment in the general population but may be effective in prevention, especially in special populations.

"In 'ordinary people,' vitamin C does not prevent colds," lead author Harri Hemilä, MD, PhD, an associate professor of Public Health at the University of Helsinki in Finland, told Medscape. "This is an important conclusion because lots of 'ordinary people' are taking vitamin C with the belief that vitamin C prevents colds. But there seem to be some groups of people who seem to get the benefit of vitamin C supplementation for a preventive purpose: people under heavy short-term physical stress are the most explicit group, which we identified in our Cochrane review."

Although vitamin C is widely used to prevent and treat cold symptoms, whether available evidence supports this common wisdom has been a subject of controversy.

"Despite 60 years of research in this area, there still seems to be little evidence to support the use of vitamin C in prevention or treatment of the common cold," Sherif Beniameen Mossad, MD, FACP, FIDSA, from Cleveland Clinic of Case Western Reserve University in Ohio, told Medscape. Dr. Mossad was not involved in the current Cochrane review but was asked by Medscape for independent commentary.

"However, given the significant heterogeneity of studies, and the shown benefit in certain situations, the possibility of benefit in other situations, or using different dosage or frequency should not be discarded," Dr. Mossad said. "Even if the only evidence of benefit for the individual that can be shown is what has been concluded from the current review, translating that to the benefit for the society is significant."

Using the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to December 2006), and EMBASE (1990 to December 2006), the authors identified placebo-controlled trials studying the effects of 0.2 g or more per day of vitamin C for cold prevention and treatment.

Two of the authors independently extracted data from these trials and evaluated their quality. Primary outcomes were incidence of colds during prophylaxis, defined as the percentage of participants having at least 1 cold during the trial period, and duration, defined as the mean number of days of illness of cold episodes.

Meta-analysis of the relative risk (RR) of developing a cold while taking prophylactic vitamin C included data from 11,350 study participants enrolled in 30 trials. In this meta-analysis, the pooled RR was 0.96 (95% confidence intervals [CI], 0.92 - 1.00).

However, in a subgroup of 6 trials enrolling a total of 642 marathon runners (4 trials), Swiss schoolchildren in a skiing camp (1 trial), and Canadian soldiers performing subarctic exercises (1 trial), pooled RR was 0.50 (95% CI, 0.38 - 0.66), which was a highly statistically significant effect.

"The 50% average for 6 studies implies benefit for some physically stressed groups of people," Dr. Hemilä said. "Our finding of 50% suggests a clinically important benefit, but I do not believe that this figure is valid for all athletes.... The groups of people who benefit — more accurately defined, how much they benefit and how much vitamin C they should take, are questions requiring further study."

In a meta-analysis of common cold duration that included 30 comparisons involving 9676 respiratory episodes, there was a consistent benefit during prophylaxis with vitamin C, with cold duration decreased by 8% (95% CI, 3% - 13%) in adults and by 13.6% (95% CI, 5% - 22%) in children.

"These findings imply that vitamin C may prevent colds when taken prophylactically in certain situations only, and reduce the duration of colds in those who develop one while taking it prophylactically, but to a small extent; more so in children than adults," Dr. Mossad said. "It has not been shown to decrease the duration or severity of colds when taken therapeutically after the onset of illness."

Interestingly, Dr. Hemilä noted that dosages in most of the adult and child studies of prophylaxis were 1 g of vitamin C per day.

"The regular supplementation studies found strong evidence that vitamin C shortens the duration of colds that occur during supplementation," Dr. Hemilä said. "Regular [supplementation] means administering vitamin C every day over the study.... I think that the adult vs children difference in [these] studies (8% vs 13.6%) is not a real subgroup difference, but is caused by the different dose per weight."

When vitamin C was started after the onset of cold symptoms, there were no significant differences from placebo in cold duration during therapy, based on 7 trial comparisons involving 3294 respiratory episodes. Similarly, in 4 trial comparisons involving 2753 respiratory episodes, vitamin C was no different than placebo in terms of cold severity during therapy.

"There are not many therapeutic studies, with supplementation starting after the onset of symptoms, and the results are not consistent," Dr. Hemilä said. "Thus, the regular supplementation studies show that vitamin C affects the duration and severity of colds, but they do not help in evaluating its practical relevance."

One study of particular importance, according to Dr. Hemilä, was performed at the National Institutes of Health by Karlowski and colleagues and published in the March 1975 issue of Journal of the American Medical Association. In a 2 × 2 factorial design, subjects received placebo, 3 g/day of prophylactic vitamin C, 3 g/day of therapeutic vitamin C for 5 days, or 3 g/day of prophylactic vitamin C plus 3 g/day of therapeutic vitamin C.

Although the authors concluded that there were no substantial differences in the effect of regular and therapeutic supplementation on the duration of colds, Dr. Hemilä reanalyzed their data and published the findings in the October 1996 issue of the Journal of Clinical Epidemiology. The 3-g/day groups had approximately the same effect and the 6-g/day group had twice this effect (17% reduction in colds), suggesting dose dependency.

"It is noteworthy that the regular supplementation study estimates (8% and 13%) are based on studies mainly using 1 g/day," Dr. Hemilä said. "Thus, these estimates should not be used as a basis to make a decision whether vitamin C is reasonable for therapy or not. Furthermore, it is a subjective issue of values and price of treatment when a person considers whether the minimum effect should be 10% or 20% or something else."

Strengths of the current Cochrane review, according to Dr. Hemilä, are the large number of placebo-controlled studies in different countries enrolling both adults and children. The main limitation is that the therapeutic effect cannot be properly estimated from the published studies because there are few therapeutic studies and they are methodologically diverse. Another limitation is that essentially all the studies were performed in developed countries where the usual dietary intake of vitamin C is high.

Dr. Mossad added that the main strengths of this review are the "extensive personal experience and insight of the authors into this topic" and the "rigorous" methodology. The limitations result from the heterogeneity of studies included with respect to diet, living conditions, climate, dose and duration of therapy.

"There is lots of individual-level experimentation in medicine," Dr. Hemilä explained. "For example, if a antihypertensive drug does not lower blood pressure in 1 person, we try another drug; we do not say that the lack of effect in 1 person is evidence that the first drug is ineffective in general. We say that it does not work for that particular person."

"With similar kind of reasoning I think vitamin C may be tried for treating colds," Dr. Hemilä concluded. "If a person does not feel there is any benefit, he or she need not take it next time. But if vitamin C seems to be helpful, there is a subjective reason to try it again the next time."

In terms of future research, Dr. Hemilä recommended well-planned therapeutic trials of vitamin C dosages well above 1 g/day, because some studies have suggested a dose-response effect with dosages up to 6 g/day. He also recommends a study duration of longer than 5 days, because a few 3-day therapeutic trials found no benefit, and he believes that the negative findings may have been caused by the short study duration.

"More accurate characterization of the 'physical stress' group needs much more research, but I think it is less important from the public health point of view compared with the therapeutic effect mentioned above," Dr. Hemilä said. "Marathon and comparable events are rare, whereas the common cold is ubiquitous among 'ordinary' people."

Dr. Mossad also recommended prophylaxis studies in other populations or under conditions that increase the risk of having colds or of having more severe colds; treatment studies in homogenous populations using a variety of experiments using larger doses, consistent early administration, or more frequent dosing; treatment studies in children; and basic science studies to further elucidate the potential biological effect of vitamin C in preventing or treating the common cold.

"It is somewhat reassuring that serious side effects have not been encountered in any of these studies," Dr. Mossad concluded. "However, as common as the common cold is, even a rare side effect may become more apparent if consistent widespread use is implemented."

Dr. Hemilä has disclosed receiving his salary from the University of Helsinki. He holds no shares and has no other financial relationships with pharmaceutical or other companies that might have interest in vitamin C or in the common cold. He has on a few occasions lectured in meetings organized by drug companies, most recently in 2004. Dr. Mossad has disclosed no relevant financial relationships.

Cochrane Database Syst Rev. Published online July 18, 2007.

Clinical Context

In the November 1971 issue of Proceedings of the National Academy of Sciences of the United States of America, a meta-analysis by Pauling indicated that vitamin C decreased the incidence of the common cold. Subsequent studies had variable results. Cochrane reviews on vitamin C for preventing and treating the common cold were published in 1998 and in 2004 by Douglas and colleagues (Cochrane Database of Systematic Reviews, issues 1 and 4, respectively). The 2004 review included studies from the 2004 CENTRAL database, MEDLINE from January 1966 to June 2004, EMBASE from 1990 to June, week 23, 2004, reference lists from systematic reviews, and a personal reference list from 1 reviewer. A limitation of the review was counting the placebo group multiple times in the pooled data. One additional publication, by Sasazuki and colleagues and published in the January 2006 issue of the European Journal of Clinical Nutrition, has been included in the current 2007 review, which includes search results through December 2006.

This current Cochrane review examines whether at least 0.2 g of daily prophylactic vitamin C affects the incidence, duration, or severity of the common cold and whether vitamin C treatment at the onset of the common cold affects the duration or severity of symptoms. In this review, placebo groups were counted only once in pooling data from trials with multiple treatment groups.

Study Highlights

56 studies were found using CENTRAL (The Cochrane Library, issue 4, 2006), MEDLINE (2004 to December 2006), and EMBASE (1990 to December 2006) databases.

Criteria for inclusion were placebo-controlled trials of at least 0.2 g of vitamin C daily to prevent or treat the common cold and adequate description of methodology and data.

Studies had to include adequate information to assess study quality based on allocation concealment, blinding, randomization, attrition, and placebo distinguishability.

Subjects included children and adults of any sex or age.

3 small laboratory studies that exposed subjects to viruses after prophylactic vitamin C or placebo were not included in meta-analysis:

1 study showed decreased incidence and symptom severity score in vitamin C group.

1 study showed decreased severity, but not duration, in vitamin C group.

1 study showed no beneficial effect in vitamin C group.

42 community studies evaluated the effect of prophylactic vitamin C on naturally acquired common cold.

11 community studies evaluated the effect of treatment with vitamin C after onset of naturally acquired common cold.

Prophylactic vitamin C had no effect on common cold incidence:

Of 11,350 subjects, 6135 subjects used vitamin C for 2 weeks to 5 years.

Pooled RR for cold infection was 0.96 (95% CI, 0.92 - 1.00).

Subgroup analysis of 6 studies showed decreased cold incidence in subjects with extreme physical or cold stress or both (marathon runners, skiers, soldiers in subarctic exercise; RR, 0.50; 95% CI, 0.38 - 0.66).

Prophylactic vitamin C decreased duration of common cold:

In 7242 illness episodes in adults, pooled decrease in duration was 8.0% (95% CI, 3.0% - 13.1%).

In 2434 illness episodes in children, pooled decrease in duration was 13.6% (95% CI, 5.6% - 21.6%).

Prophylactic vitamin C slightly and inconsistently decreased severity of common cold:

Severity measured as days confined indoors or off from work or school decreased (P = .02).

Severity measured as symptom severity score did not decrease.

Pooled severity, measured as days off and symptom score, decreased (P = .004).

Treatment with vitamin C after onset of common cold did not decrease duration of symptoms in data from 3294 illness episodes:

In 1 study, illness duration of only 1 day was more common with vitamin C at 8 g/day vs 4 g/day (46% vs 39%; P = .046) and illness duration was shorter if treated with vitamin C within 24 hours of illness vs with other medications (3.6 vs 6.9 days).

Treatment with vitamin C after onset of common cold did not decrease severity of symptoms in data from 2753 illness episodes.

No serious adverse events were reported.

Adverse effects were similar for 2490 subjects receiving high-dose vitamin C (1 g/day) vs 2066 subjects receiving placebo (5.8% vs 6.0%).

Exclusion of studies with inadequate allocation concealment had no significant effect.

Pearls for Practice

The effects of oral prophylactic vitamin C on the common cold include decrease in duration, especially in children; slight decrease in severity; and no decrease in incidence, except for a subgroup of persons exposed to extreme cold or physical stress.

Vitamin C treatment of the common cold has no significant effect on duration or severity of illness.

        

Dr. José Manuel Ferrer Guerra

Any Degree of Albuminuria Signals Increased Cardiovascular Risk

News Author: Sue Hughes

CME Author: Désirée Lie, MD, MSEd

November 26, 2007 — Albuminuria, even in low levels within the "normal" range, is an independent predictor of cardiovascular and all-cause mortality, a new analysis of the Prevention of Events with an ACE inhibitor (PEACE) trial shows.

The study, published online November 19, 2007 in Circulation and scheduled for its December 4, 2007 issue, was conducted by a group led by Dr Scott Solomon (Brigham and Women's Hospital, Boston, MA).

Solomon commented to heartwire: "We found that virtually any degree of albuminuria, even albumin below the level we call microalbuminuria, placed a patient at significantly higher risk of cardiovascular events. A number of other studies have been suggestive of this — HOPE [Heart Outcomes Prevention Evaluation] in higher-risk vascular disease patients and LIFE [Losartan Intervention for End Point Reduction] in hypertension patients — but ours was a particularly low-risk population, so we've extended the findings to this low-risk group with stable CHD [coronary heart disease]. We should stop thinking about cut-off values for microalbuminuria. If albumin is detectable in the urine, the patient is at increased risk."

A new window to the health of the vasculature

Solomon explained that as such low levels of albumin cannot be detected with a dipstick test, they used a spot assay that measures the urinary albumin-to-creatinine ratio (ACR), which gives a more accurate measure of albumin status, as it takes into account the fact that the concentration of albumin in urine varies, depending on the amount of water consumed. "This is still a very easy, noninvasive, and cheap test. All you need is a urine sample. We do many far more invasive and expensive tests than this to risk-stratify patients. This test gives us a new window to the health of the vasculature that we should take advantage of," he added.

Noting that a previous analysis of the PEACE population had shown that a reduced glomerular filtration rate (GFR) was also associated with increased cardiovascular risk, Solomon said: "We have now shown that both measures of kidney function are markers of increased risk. If either one is compromised, then risk is increased, and if both are affected, then risk is very much increased. These two studies are telling us that we cardiologists need to pay more attention to kidney function in our patients and to understand that these are not patients who will ever come to dialysis or even necessarily see a nephrologist, but they do have mild kidney disease that puts them at increased risk for a cardiovascular event."

He pointed out that whether or not patients with minor renal dysfunction should be treated differently is open to debate but added: "There is a fair amount of evidence that inhibitors of the renin angiotensin system and ACE [angiotensin-converting enzyme] inhibitors in particular are of benefit to CHD patients with reduced renal function. So I would say that if you are undecided about whether to give an ACE inhibitor or not, this test could help you make that decision."

A measure of treatment efficacy

In the paper, the authors also note that microalbuminuria may represent an early marker of diffuse vascular endothelial dysfunction, and clinicians should consider serial quantification of ACR as a marker of risk, because its reduction may be a metric of treatment efficacy.

The main PEACE trial evaluated the effects of trandolapril vs placebo in 8290 patients with stable coronary artery disease and normal left ventricular ejection fraction. In the current analysis, the urinary ACR was assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months). The majority of patients (73%) had a baseline ACR within the normal range (<17>

Results showed that independent of the estimated GFR and other baseline covariates, a higher ACR, even within the normal range, was associated with increased risks for all-cause mortality (p<0.001) p="0.01).">

While the effect of trandolapril therapy on outcomes was not modified significantly by the level of albuminuria, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 vs 14.6 µg/mg, p=0.0002). Solomon suggested that the power of this analysis may have been insufficient to show an effect of trandolapril on outcomes. "We did see an effect of the drug on albuminuria and a definite relationship between degree of albuminuria and outcomes, but we probably had too few patients to show an actual relationship between trandolapril and outcomes," he commented to heartwire.

Source

Solomon S D, Lin J, Solomon C G et al. Influence of albuminuria on cardiovascular risk in patients with stable coronary artery disease. Circulation. 2007. Published online before print. November 19. DOI: 10.1161/CIRCULATIONAHA.107.723270

The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

Clinical Context

Patients with chronic renal disease are at increased risk for cardiovascular morbidity and mortality. Albuminuria, a marker of renal and systemic vascular disease, is a significant predictor of cardiovascular risk in patients with and without diabetes. However, albumin excretion below the traditional microalbuminuria range, which is not detectable by albumin dipstick testing but is detectable by spot urine ACR, may also be predictive of cardiovascular risk independent of other measures of renal function, and this association is not well studied.

This is a study within the PEACE trial to examine the association between baseline ACR and subsequent cardiovascular and all-cause mortality in patients with stable CAD randomized to receive either trandolapril or placebo and followed up for a mean of 4.8 years.

Study Highlights

• Included were 8290 patients aged 50 years or older with documented CAD and a left ventricular ejection fraction of more than 40% who were randomized to receive trandolapril or placebo and who were followed up for a mean of 4.8 years.
• Excluded were those hospitalized for unstable angina within 2 months, had coronary revascularization within 3 months, had planned coronary revascularization, or had a serum creatinine level of more than 2.0 mg/dL.
• At baseline, patients completed a questionnaire on medical history, medications taken, and lifestyle risk factors and had anthropomorphic and blood pressure measurements.
• Serum and spot urine specimens were obtained at baseline from 2977 patients, and follow-up samples were repeated in 1339 patients after 34 months.
• Urine and serum specimens were tested by personnel blinded to clinical outcomes and treatment allocation.
• Primary outcomes were all-cause and cardiovascular mortality and the PEACE composite outcome of cardiovascular death, nonfatal myocardial infarction, and coronary revascularization.
• Albuminuria was categorized as low to medium microalbuminuria (25.0 - 177.0 µg/mg in women and 17.0 - 125.0 µg/mg in men) and high microalbuminuria to macroalbuminuria (> 177.0 µg/mg in women and 125.0 µg/mg in men).
• The majority of patients (73%) had ACR within the normal range (<>
• Higher baseline ACR was associated with older age, male sex, nonwhite race, history of angina, diabetes, hypertension, smoking, elevated blood pressure, previous revascularization, lower estimated GFR, and less use of calcium channel blockers and aspirin.
• Higher baseline ACR, even within the normal range, was associated with higher rate of all-cause mortality and cardiovascular death in both treatment groups, independent of estimated GFR (P < .001).
• Use of trandolapril was associated with significantly lower ACR with time.
• The effect of trandolapril therapy on outcomes was not modified significantly by the level of albuminuria.
• An increase in ACR with time was associated with increased risk for cardiovascular death (hazard ratio [HR] per log ACR, 1.74).
• The presence of diabetes mellitus (HR, 1.62; P = .002), current smoking (HR, 2.16; P < .001), and an estimated GFR of less than 60 mL/minute/1.73 m2 (HR, 1.64; P = .004) was independently associated with mortality, whereas body mass index (BMI) was not.
• There was a weak inverse relationship between ACR and estimated GFR.
• A higher ACR was associated with increased rates of mortality in patients with normal and reduced estimated GFR.
• For the 1339 patients who received repeat urine testing at 34 months, trandolapril therapy was associated with a significantly lower adjusted mean follow-up ACR (mean, 12.5 vs 14.6 µg/mg; P = .0002).

Pearls for Practice

Higher baseline ACR, even within normal values in patients with stable CAD, is associated with higher all-cause and cardiovascular mortality, and increase in ACR with time is associated with higher mortality.

Diabetes mellitus, current smoking, and an estimated GFR of less than 60 mL/minute/1.73 m2 but not BMI are associated with higher mortality in patients with stable CAD.

        

Gracias Dr. José Manuel Ferrer Guerra

Highlights in Liver Disease

Introduction

The 2007 meeting of the American College of Gastroenterology (ACG) provided a forum for the presentation of current research findings in clinical gastroenterology and hepatology for nearly 4000 attendees from around the world. This report highlights some of the key data in liver research, ranging from issues in transplantation and viral hepatitis to acute liver failure and applications of imaging technology.

Liver Transplantation

Smith and Gentile[1] reviewed the US Scientific Registry of Transplant Recipients for patients awaiting liver transplantation between the years 1998 and 2002 to determine the proportion of black transplant recipients who underwent transplantation for primary sclerosing cholangitis as compared with nonblack recipients. Although 5.45% of the total recipients had primary sclerosing cholangitis as an indication for transplantation, black patients were more likely to be transplanted for their liver disease than nonblack patients during the period of observation. Although it may be that black patients were sicker by the time of listing for transplantation, it is also possible that they had more aggressive disease than the nonblack patients.

The investigators did not identify whether there were more individuals with cholangiocarcinoma among the population of black patients with primary sclerosing cholangitis than among the nonblack group. We need to keep this potential for rapidly progressive disease in mind as we care for patients with primary sclerosing cholangitis and ensure that we consider early referral for transplantation with any sign of decompensation, such as ascites, encephalopathy, or variceal hemorrhage -- especially among the black population.

Chronic Hepatitis C

In a retrospective review of 512 patients with hepatitis C who underwent screening for hepatocellular carcinoma by ultrasound assessment, 15 were identified with asymptomatic dilatation of the common bile duct (CBD; mean diameter, 9.8 mm ± 2 mm).[2] Of these 15 patients, 12 were on methadone maintenance. Of the total population screened, 65 were on methadone, 12 (18.5%) of whom had asymptomatic CBD dilatation. In comparison, only 3 of 447 (0.67%) patients not on methadone had dilatation of the CBD. Ten of the 12 patients on methadone with CBD dilatation had normal alkaline phosphatase levels; the remaining 2 patients had either a normal endoscopic retrograde or magnetic resonance cholangiogram. Two patients had an elevated total bilirubin level, which was predominately due to indirect bilirubin, and 2 of the 12 patients had cholelithiasis with no associated choledocholithiasis. Cirrhosis may or may not have been present, as this parameter was not used as an indication for ultrasound surveillance in this population. These findings indicate that asymptomatic CBD dilatation may be present in patients on methadone and that extensive work-up for other etiologies for bile duct dilatation may not be needed.

There is often limited participation by black patients in hepatitis C clinical trials. In an attempt to determine the factors that may lead to such underrepresentation, 80 subjects (56 black and 24 white patients) with hepatitis C were recruited from a major university liver clinic and from a nearby internal medicine clinic and interviewed about their attitudes in regard to participation in research trials.[3] Black patients were more likely to lack insurance and to not have available transportation to attend clinical care. Both of these factors were significantly different from the white patients. No differences were observed in trust or religiosity between blacks and whites. These data suggest that both transportation and lack of available financial coverage may be factors that reduce participation by black patients in hepatitis C trials, and that we should consider transportation when seeking participation of patients in clinical trials.

Patients infected with hepatitis C virus (HCV) genotype 3 have an 80% or better response rate to treatment with pegylated interferon and ribavirin. However, the reason the remaining 20% of patients fail to respond is often not clear. In a study involving 34 treatment-naive patients with HCV genotype 3 infection -- 16 of whom were nonresponders to treatment -- sex; age; body weight; comorbidities, such as diabetes mellitus; and baseline HCV RNA and alanine aminotransferase (ALT) levels were evaluated.[4] When studied by univariate and multivariate analysis, only age remained as a factor associated with nonresponse to therapy (ie, therapy response is negatively affected by increasing age). This finding is similar to data reported for other HCV genotypes, in which age is an important reason for nonresponse. Regardless, age should not be a factor in refusing to treat an HCV-positive patient infected with any HCV genotype.

Chronic Hepatitis B

Reactivation of hepatitis B virus (HBV) disease can occur following chemotherapy for malignancies, such as lymphoma.[5] Patients at highest risk seem to be those with hepatitis B surface antigen (HBsAg) positivity, with the risk proportional to HBV load. In addition, some patients who are antihepatitis B core (HBc) antibody-positive are also at risk for HBV reactivation. Reactivation of HBV-related acute liver disease occurs due to the increase in viral load that develops during the immunosuppression induced by the chemotherapy. This results in increased infection of liver cells by HBV and leads to enhanced liver cell necrosis when immune function improves following the cessation of the chemotherapy. The current guidelines on prevention of reactivation suggest that patients at risk for HBV reactivation should receive preemptive antiviral therapy with lamivudine during chemotherapy, and for an additional 6 months after chemotherapy.[6]

To assess whether oncologists are knowledgeable about reactivation of HBV infection, investigators conducted a survey of oncologists in the Washington, DC area.[7] Although 78% of clinical oncologists were aware of the risk for reactivation of acute HBV disease, only 30% indicated that they had seen a patient with reactivation during or after chemotherapy. Furthermore, most did not screen patients with risk factors for HBV disease for HBsAg or anti-HBc positivity. These data suggest that we need to ensure that established guidelines for screening are applied by oncologists when chemotherapy is planned. It has been suggested that guidelines similar to those for screening pregnant patients for hepatitis B may be ideal, and should include first-generation immigrants from the Far East or sub-Saharan Africa; illicit drug users; those with multiple sexual partners; those with tattoos, especially if they are self-administered; those with abnormal liver tests; those with HIV or HCV infection; homosexual males; and individuals with a history of incarceration; etc. In these high-risk groups, identification of prior or current infection with HBV should lead to treatment with lamivudine, adefovir, telbivudine, or entecavir during and following chemotherapy.

Acute Liver Failure

Acute liver failure can occur following a number of events, including infection with the hepatitis viruses (A, B, E, and rarely C); infection with herpesvirus and parvovirus; the use of drugs, such as acetaminophen, antibiotics, and nonsteroidal inflammatory drugs; after administration of anesthetic agents; after ischemia, including left heart failure and hypoxemia; and in association with some chronic diseases, such as autoimmune hepatitis or Wilson's disease.[8,9] The outcome of acute liver diseases, such as those associated with acetaminophen overdose, ischemia, or hepatitis A, tends to be better, improving spontaneously, vs all other etiologies. Unfortunately, however, understanding when to intervene with liver transplantation remains difficult to ascertain as the patient develops increasing encephalopathy. The US Acute Liver Failure Study Group has collected data on more than 1100 patients with acute hepatic failure and has begun to model prognosis to identify those factors indicating that salvage with liver transplantation is required.[10] By controlling for both etiology and for a coma score equivalent to Childs-Pugh classification III (Childs-Pugh C), the investigators determined that death or liver transplantation need was associated with a higher serum creatinine and bilirubin level, a higher international normalized ratio, a lower blood pH, and an unfavorable etiology of acute liver injury (ie, not acetaminophen-, hepatitis A-, or ischemic liver injury-associated). These factors are essentially those of the Model for End-Stage Liver Disease (MELD) score, which is used for establishing the stratification of patients with chronic liver disease for liver transplantation. Although factors other than scoring models should also be considered, a model that is predictive of the requirement for liver transplantation will be important in the provision of care. Most important, as a rule of thumb, patients with suspected acute liver failure should be considered for immediate referral to a liver transplant center.

Magnetic Resonance Cholangiopancreatography

Three studies were presented from the same clinical site assessing the effectiveness of magnetic resonance cholangiopancreatography (MRCP) in the evaluation of patients with pancreaticobiliary disease. In the first, the diagnostic accuracy of MRCP was compared with endoscopic retrograde cholangiopancreatography (ERCP), defined as the "gold standard" for the diagnosis of suspected biliary strictures and choledocholithiasis.[11] Of 94 patients (including 27 with choledocholithiasis and 34 with benign or malignant strictures), MRCP reported 7 false positives and 3 false negatives for choledocholithiasis, for a sensitivity of 89%, a specificity of 90%, and an accuracy of 89% for the diagnosis of choledocholithiasis. For bile duct strictures, MRCP resulted in 1 false-positive and 3 false-negative studies, yielding a sensitivity of 91%, a specificity of 98%, and an accuracy of 96%. These findings suggest that MRCP is effective for the diagnosis of biliary tract disease; however, it is less effective for the diagnosis of CBD stone disease, and ERCP may still be needed for the accurate diagnosis of some patients.

In a second study,[12] this same group identified 184 patients who underwent both MRCP and ERCP during the 5-year study period for evaluation of pancreatic and biliary disease. ERCP was again used as the gold standard. The investigators found a concurrence of findings in 85.3% of cases. In comparison, however, MRCP and ERCP disagreed in diagnosis in 13 of 27 cases of choledocholithiasis, 6 of 27 biliary strictures, 4 of 27 biliary tree anomalies, and in 2 of 27 cases of biliary malignancy. In a subsequent study, MRCP demonstrated greater accuracy in the diagnosis of patients with pancreatic disease vs suspected biliary tract disease.[13]

Collectively, these studies suggest that although MRCP is generally a useful and effective diagnostic study in patients with pancreatic and biliary disease when compared with ERCP as the gold standard in the same population, this imaging modality is more likely to be inaccurate in patients with choledocholithiasis and demonstrates a similar accuracy to ERCP for the diagnosis of pancreatic disease. I continue to use MRCP as my first-line diagnostic study for biliary tract disease unless the signs and symptoms of the patient strongly indicate that choledocholithiasis is present. In these patients, an ultrasound exam may be adequate and more cost-effective in assessing for choledocholithiasis prior to consideration of ERCP and therapy.

Venous Thrombosis in Cirrhosis

It seems logical that patients with cirrhosis and attendant portal hypertension with thrombocytopenia and altered coagulation would be less likely to develop deep venous thrombosis and venous thromboembolism than the general population. In a case-controlled retrospective study, patients with cirrhosis were matched with patients lacking cirrhosis and assessed for diagnoses of pulmonary embolism.[14] Patients on warfarin or with a past history of pulmonary embolism were excluded. The presence of cirrhosis was established by liver biopsy or implied by imaging studies consistent with cirrhosis. International Classification of Diseases, Ninth Revision (ICD-9) codes for venous thromboembolism were used to identify affected patients and confirmed by chart review for findings on Doppler ultrasound, ventilation-perfusion scans, and/or computerized tomography of the chest. Among patients with cirrhosis, 1.8% experienced thromboembolism compared with 0.9% of controls. When controls with chronic diseases were separately identified, thromboembolic disease was seen in 7.1% of patients with chronic kidney disease, 7.8% of patients with congestive heart failure, and in 6.1% of patients with cancer. These data indicate that although patients with cirrhosis have a reduced risk for venous thromboembolism when compared with patients with other chronic diseases, they are at increased risk when compared with a general population of patients lacking chronic disease. Thus, patients with cirrhosis should be considered for anticoagulation prophylaxis when hospitalized or when they are at increased risk for venous thrombosis.

Potpourri

One of the continuing concerns among patients with end-stage liver disease, such as cirrhosis, is whether the use of acetaminophen will cause worsening of their cirrhosis and lead to decompensation. Ninety patients admitted with decompensated cirrhosis were compared with 125 nondecompensated, cirrhotic outpatients, and analgesic use, alcohol use, and dietary and medication compliance in the prior 30 days were assessed by history.[15] Alcohol use, dietary factors, and other medication effects were assessed to control for other factors that can add to decompensation risk of the patients. There was no difference in the frequency of analgesic use between the decompensated and compensated patients, suggesting that acetaminophen or other analgesics did not worsen their liver disease and lead to decompensation. The investigators did not determine the average daily dose of acetaminophen in either group, and the long-term use prior to the past 30 days was also not assessed. At this point, I believe that we should still instruct our patients with cirrhosis to limit their acetaminophen and nonsteroidal anti-inflammatory drug use. I generally permit my patients with end-stage liver disease to use no more than 2 g of acetaminophen daily in divided doses.

Many clinicians have had concerns about the use of statins in patients with abnormal liver tests. In an analysis of the HCV registry at a Veterans Affairs hospital, patients who completed at least 12 weeks of therapy with pegylated interferon and ribavirin were evaluated for concomitant statin use.[16] No worsening of liver enzyme levels was observed in this small group of patients who were using statins during HCV therapy. This issue often comes up in patients with HCV infection or nonalcoholic steatohepatitis who have a high cholesterol level. I would suggest that the patient with mild abnormality of liver enzyme levels is not at significantly increased risk for drug-induced hepatitis and can be started on statin therapy and followed with periodic liver studies. Current guidelines recommend monitoring of aminotransferase levels in those with abnormal liver tests when statins are initiated.[17] If there is an increase in aminotransferase level, the potential role of the statin should be determined, but it is not likely to result in overt severe liver injury.

Supported by independent educational grants from Abbott and Shire

        

Gracias Dr. José Manuel Ferrer Guerra

Applications of Acid-Suppression Therapy in GERD/Acid-Related Disorders

Introduction

The approach to the patient with gastroesophageal reflux disease (GERD) revolves around accurate diagnosis and optimal use of available therapies. The diagnosis is made by a combination of the history (symptom presentation), response to a therapeutic trial, and judicious use of diagnostic tests. These tests include endoscopy, reflux monitoring (pH, impedance) and, in some cases, esophageal function testing (manometry and or barium x-rays). Therapy, whether medical, surgical, or endoscopic, is aimed at relief of symptoms and prevention of complications. This year's meeting of the American College of Gastroenterology (ACG) featured a number of presentations addressing these topical clinical issues. This report summarizes some of the more key data.

Dysplasia in Fundic Gland Polyps

Recent reports have brought to the fore a number of issues regarding the long-term use of proton-pump inhibitors (PPI). Concerns about an increased risk for hip fractures, enteric infections, and pneumonia have rekindled old questions about the long-term safety of this incredibly effective class of drugs.[1-3]

One area that has received attention periodically is the finding of fundic gland polyps in the stomach of GERD patients who are on long-term PPI therapy. To date, most "experts" regard these polyps as universally benign and do not offer recommendations for a change in therapy. Some, however, raise concern about the potential risk for these polyps over time. Therefore, a study investigating the potential for and prevalence of dysplasia in fundic gland polyps among patients with familial adenomatous polyposis (FAP) may shed some light on this area.[4] Although these findings may not be translated to patients without FAP, the results are noteworthy because of the frequency of fundic gland polyps in patients taking PPIs. The authors found that dysplasia was more common in patients with more than 30 polyps (odds ratio [OR], 9.44; 95% confidence interval [CI], 0.96-92.55) and was negatively associated with PPI/histamine-2 receptor antagonist use (OR, 0.15; 95% CI, 0.02-0.95). Overall, no cancers were found in the cohort studied, and the majority of dysplasia was low-grade. The fact that taking PPIs was associated with a decrease in risk for dysplasia in fundic gland polyps should alleviate concerns about the risk for dysplasia in non-FAP patients with fundic gland polyps who are on long-term PPI therapy.

Endoscopic Full-Thickness Plication for GERD

The use of endoscopic therapy for GERD has met with limited success. Initially greeted with enthusiasm, early studies raised promise for several endoscopic approaches. However, as of this writing, only 2 such therapies remain active and FDA-approved: radiofrequency ablation and endoscopic plication. The former is rarely used. The newest procedure to be evaluated in this setting is endoscopic full-thickness plication. This endoscopic technique has been shown in short-term observational studies and in one sham trial to be effective in relieving heartburn, in improving GERD-related quality of life, and in decreasing PPI use 6-12 months after treatment.[5] If safe and effective, this procedure would offer an alternative to surgery not currently available for those patients who do not wish to take, cannot tolerate, or cannot afford PPIs. A study presented at ACG 2007 reported on the 5-year outcome of a cohort of patients from the original open-label trial on treatment durability post plication.[6] Twenty-eight (of 64) subjects completed long-term follow-up (50-65 months); at 5 years post procedure, 62% remained off daily PPI therapy. Perhaps the most important feature of these uncontrolled observations was that the treatment effect remained stable between years 3 and 5. Thus, patients off daily PPI therapy at 3 years post procedure were still off PI therapy at 5 years. Quality-of-life scores improved from baseline and remained stable after 3-5 years. Despite methodologic flaws, including a sizable number of dropouts and that the study was not designed for long-term follow-up, these findings suggest that some patients will improve over the long term and perhaps will maintain their improvement with this type of plication procedure. Such results suggest some light in a previously dark tunnel for endoscopic therapy and offer hope that soon we may have an effective and safe alternative to medical or surgical therapy for GERD. Patients wishing to consider this treatment should be referred to centers of excellence in these procedures, as they should for antireflux surgery.

Sensed Acid Reflux Events in Different GERD Groups

GERD patients are traditionally divided into 2 categories: those with erosive esophagitis and those with nonerosive esophagitis. While in many cases this division is trivial, there are sufficient differences in response to PPI therapy among these 2 groups to raise questions about the pathogenesis of symptoms: Are they different in erosive esophagitis compared with nonerosive esophagitis? In addition, we have become increasingly aware of a "third" group of patients with chronic heartburn -- a group of patients with minimal PPI response, normal endoscopy, and normal prolonged pH monitoring studies. This latter group, whose condition is referred to as functional heartburn for lack of a better term, is considered to not have GERD as the etiology of their symptoms. It has never been clear whether or how these GERD groups are different.

A study assessing 50 patients with heartburn symptoms occurring more than 3 times per week provided insight into the genesis of heartburn, the primary and most frequent of GERD symptoms across all of the above groups.[7] Twenty-two patients had erosive esophagitis, 15 had nonerosive reflux (abnormal pH, normal endoscopy), and 13 had functional heartburn (normal pH, normal endoscopy). All patients underwent 24-hour multichannel pH monitoring (1, 6, 11, and 16 cm above the lower esophageal sphincter [LES]) off PPI therapy to investigate whether there were any distinguishing features in the production of heartburn between these 3 groups. The authors reported that proximal reflux (≥ 11 cm above the LES) was most likely to produce symptoms. This finding was common among all groups, including those patients with so-called functional heartburn. This study reinforces the importance of proximal reflux in the genesis of symptoms. The authors provided important insight into understanding that some patients will have acid-related heartburn despite having poor response to therapy and have no evidence of abnormal reflux either on pH monitoring or endoscopy. Perhaps some patients are sensitive to esophageal distention, muscle contraction, or stretch, with proximal acid as the trigger in the absence of prolonged or excess reflux. Therapy aimed at reducing reflux height, the frequency of proximal acidic reflux episodes, and acid sensitivity needs to be explored.

Reflux-Related Persistent Cough

Evaluation of the patient with chronic cough often includes a search for GERD as the etiology of symptoms. An empiric trial of high-dose PPIs (usually twice a day) is the usual first-line approach in this setting. In patients with continued symptoms despite acid suppression, there is controversy regarding the best approach to diagnosis and treatment. Many suggest that no testing be performed because the tests are uncomfortable, continued acid reflux is quite rare, and because response to antireflux surgery is variable at best. Others advocate aggressive testing with prolonged reflux monitoring, including a search for nonacidic or weakly acidic reflux using combined multichannel intraluminal impedance and pH (MII-pH) monitoring. Those clinicians who favor the latter approach make the case that additional medical therapy aimed at reducing the number of reflux episodes or the use of antireflux surgery may afford improvement in individual patients. In a study presented at ACG 2007, the cost-effectiveness of 2 approaches was tested using a cost-utility model applied over a 3-year time frame.[8] The investigators compared 24-hour MII-pH testing vs no testing. Using the published literature on the frequency of abnormal MII-pH studies to define the care process, the authors found substantial cost savings if MII-pH testing was performed in patients with cough refractory to PPI therapy, especially if antireflux surgery was performed in appropriate candidates. These data provide additional support for testing to rule out nonacid reflux as a cause of refractory GERD symptoms. However, many of the assumptions in this cost-utility model are based on small studies with limited follow-up. The timeframe (3 years) is short in a patient with a chronic disease who is prone to relapse. As such, the results need to be viewed with caution. Although this author's current approach to managing these often difficult patients is to perform MII-pH testing, the clinical value of this approach can be questioned due to lack of prospective data. We need to be aware that many clinicians see patient populations in referral practices that may not be reflective of mainstream practice.

Wireless pH Monitoring

Ambulatory pH monitoring of patients with suspected GERD has been advanced by the availability of capsule-based technology. The majority of data addresses patients studied off PPI therapy. In modern gastroenterology practice, patients are most often seen already on PPI therapy with continued symptoms. The utility of prolonged pH monitoring in this group has been investigated infrequently. Two studies presented at this year's ACG meeting addressed the utility of 48-hour telemetry (wireless) capsule monitoring in patients with GERD-like symptoms who were on PPI therapy. In the first study,[9] the wireless pH capsule provided new information in 72% of patients, changed the diagnosis in 22%, and altered management in 58%. Management changes varied and included referral for antireflux surgery as well as stopping, changing, or increasing the dose of a medication. The second study[10] found a surprising number of patients who still had abnormal total acid exposure (7.7%-15.5% total time, normal <>

A Novel Catheter-Based pH Monitoring System

Reflux monitoring is often performed in patients with ear-nose-throat symptoms suspected to be due to GERD in order to evaluate for continued reflux. Many clinicians still suggest that it is important to assess reflux height, and some contend that hypopharyngeal monitoring is crucial to the adequate evaluation of these patients. Unfortunately, hypopharyngeal monitoring is difficult with traditional pH catheters; these devices are uncomfortable and are subject to technical difficulties that call into question the reliability of the data generated. A novel pH monitoring device has been developed that measures pH changes in the hypopharynx using a sensor to detect aerosolized acid. The device can be conveniently placed in the hypopharynx without the need for manometry or endoscopy. Early studies suggest that the probe is comfortable for patients and provides reliable recordings. Two studies presented at ACG 2007 sought to establish normal values for the application of this diagnostic device and compared its accuracy against that of a standard pH probe. Thirty-one normal subjects were studied with the device and 11 GERD patients underwent distal pH monitoring (5 cm above LES)[11,12] The normals were studied with dual-channel monitoring to ascertain accuracy and normal values for the hypopharynx. Normative values for this new pH catheter probe compared favorably vs those obtained with the standard pH catheter; this novel pH monitoring device was able to detect pH events in the distal esophagus (pH <>

Does Body Mass Index Affect Healing of Erosive Esophagitis?

It has become increasingly clear that there is an association between GERD and obesity. Patients with GERD who are overweight tend to have more erosive esophagitis and a higher rate of GERD complications. Symptoms tend to be more frequent in patients who gain weight. However, the effect of obesity on symptom resolution in patients treated for GERD with PPI therapy has not been well studied. Data presented from 2 studies encompassing 704 patients with nonerosive reflux disease were pooled and analyzed.[13,14] Patients were treated with esomeprazole (20 or 40 mg once daily) or placebo. Heartburn severity at baseline and heartburn resolution at the end of the study (last 7 days) were assessed as a function of BMI. Patients were divided into 3 groups: BMI <> 35 kg/m2. There was no association between heartburn severity, heartburn resolution, and baseline BMI. This is the first study to address this clinical subject, albeit in a post-hoc analysis. These findings prompt the need for prospective studies in which patients are stratified by BMI and carefully followed. However, despite this methodologic issue, these data suggest that PPI dose does not need to be altered in patients who are overweight. A post-hoc analysis of a multicenter, double-blind, parallel-group randomized trial assessed the effect of BMI on healing of erosive esophagitis in 560 patients randomized to rabeprazole 20 mg or omeprazole 20 mg once daily for 4-8 weeks. Subjects were stratified by BMI as normal (BMI ≤ to 25 kg/m2) or overweight (BMI ≥ 25 kg/m2). There was no difference in healing of erosive esophagitis between treatment groups within each BMI category (88.9%-98.6% healed overall) and no difference in time to first day of satisfactory heartburn relief or percent of complete relief. The range of BMI (other than ≥ 25) was not described. However, healing rates are in keeping with those reported in the body of GERD literature and thus further reinforce that a change in PPI dose is not likely needed in the overweight patient with GERD.

A Novel PPI

It is recommended that patients with GERD take PPIs prior to a meal (15-30 minutes) to optimize efficacy. This regimen is inconvenient for some patients and may affect adherence to therapy. A new PPI currently undergoing investigation in clinical trials, TAK-390MR,* uses a modified-release technology to provide prolonged plasma concentrations of drug. The authors studied the effect and timing of food on the pharmacokinetics and pharmacodynamics (pH control) of this new PPI.[15] They tested 4 dose timings: fasting, 30 minutes after breakfast, and 5 and 30 minutes prior to breakfast. No difference was seen in mean intragastric pH among the 4 groups. Change in baseline pH was slightly greater in the fasting and 30-minutes-before-breakfast groups compared with the after-breakfast group; however, the overall differences were small. These findings suggest that intragastric pH control may be similar with this modified-release product regardless of meal timing and, perhaps as important, they suggest that this agent may be administered in the absence of food. If this agent receives FDA approval, it may offer a versatility in dosing not presently available with other PPIs.

Nocturnal Gastric and Nocturnal Esophageal Acidity in GERD

Immediate-release omeprazole (OME-IR) has been shown to provide more rapid and sustained control of overnight intragastric pH when dosed at bedtime (10:00 PM) as compared with esomeprazole 40 mg or lansoprazole 30 mg given at a comparable time (10:00 PM).[16] In a report presented at ACG 2007, the authors analyzed gastric and esophageal pH studies from 49 patients with nighttime GERD symptoms and compared integrated acidity and time pH <>

Conclusión

Studies presented at this year's ACG meeting addressed multiple issues in the approach to, and management of, patients with symptoms suspected to be due to GERD. The relationship between GERD and obesity was reinforced with the presentation of new information addressing treatment of the overweight population. The importance of proximal propagation of the gastric refluxate in the genesis of symptoms was underscored by new data on the value of impedance/pH testing and early data on the potential utility of a novel pH probe. Long-term data on the latest endoscopic therapy provides hope that these techniques will find a place in the long-term management of GERD. Finally, data addressing a more versatile PPI formulation suggest that if this agent becomes available, it may aid in the management of a disease for which therapy must be individualized.

*The US Food and Drug Administration has not approved this medication for this use.

Supported by independent educational grants from Abbott and Shire

        

Dr. José Manuel Ferrer Guerra