Day: 12/18/2010

Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

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Aims

No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker.

Methods

We monitored a 15-year-old boy diagnosed to have FLHCC by measuring the common markers alanine aminotransaminase, alkaline phosphatase, lactate dehydrogenase, and bilirubin, as well as vitamin B12 (B12), and the forms of the B12 binding proteins. Tumour biopsies were examined immunohistologically. DNA and RNA were extracted from tumour and normal tissue and examined for content of HC DNA and mRNA.

Results

The only markers indicative of disease progression were HC and (B12), levels of which were markedly elevated to 84 (11) nmol/L at the time of diagnosis and returned to values within the reference interval (0.43 (0.33) nmol/L) after an apparently radical removal of the tumour. The disappearance rate of HC followed a biphasic curve, the unsaturated protein displaying a half-life of 2.8 days and B12 and saturated HC one of 13 days. Before each diagnosed relapse, an increased concentration of HC was observed. We found a strong immunoreaction against HC in tumour tissue and a high mRNA expression of HC supporting the notion that HC was tumour derived.

Conclusions

Plasma HC proved to be a useful tumour marker in a patient with FLHCC, and we suggest the use of this protein as a marker of disease progression in these patients.


Associations between pain and current smoking status among cancer patients

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There is growing empirical and clinical interest in purported associations between smoking and the aggravation of cancer symptoms and treatment side effects, such as pain. Both pain and smoking are highly prevalent among persons with cancer, and there is recent evidence to suggest that cancer patients who continue to smoke despite their diagnosis experience greater pain than nonsmokers. Accordingly, the main goal of this cross-sectional study was to examine associations between multiple levels of smoking status and several pain-related outcomes among a sample of 224 cancer patients about to begin chemotherapy. Patients completed self-report measures of pain severity, pain-related distress, and pain-related interference, as well as a demographics questionnaire. Results indicated that persons who continued to smoke despite being diagnosed with cancer reported more severe pain than never smokers, F (2, 215) = 3.47, p < .05. Current smokers also reported greater interference from pain than either former or never smokers, F (2, 215) = 5.61, p < .01. Among former smokers, an inverse relation between pain severity and the number of years since quitting smoking was observed, r (104) = −.26, p < .01. These data suggest that continued smoking despite a cancer diagnosis is associated with greater pain severity and interference from pain; however, future research is warranted to determine the directionality of this relationship.

Budesonide for Autoimmune Hepatitis

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Budesonide was superior to prednisone at inducing remission with fewer steroid-specific adverse effects.

Autoimmune hepatitis (AIH) is a chronic liver disease associated with excess morbidity and mortality. The mainstay of AIH therapy is prednisone plus azathioprine. However, both short-term and long-term use of prednisone can cause adverse effects. A potential alternate AIH treatment is budesonide, a steroid with high liver exposure but low systemic exposure that proved in a pilot study to be effective in previously untreated AIH patients.

Now, researchers have conducted an industry-supported, double-blind, randomized, controlled, multicenter, phase IIb trial of budesonide involving 203 noncirrhotic patients with AIH. In part one of the study, patients received azathioprine (1–2 mg/kg/day) plus either prednisone (40 mg daily, tapering to 10 mg) or budesonide (3 mg, 2–3 times daily) for 6 months. Patients who achieved complete biochemical response by 3 months — and, at the investigator’s discretion, those not in remission by 6 months — could proceed to part two of the study, a 6-month, open-label segment in which all patients received azathioprine and budesonide.

At 6 months, more patients in the budesonide group than in the prednisone group achieved the primary endpoint: complete biochemical response (normalization of liver enzymes) and the absence of steroid-specific adverse effects, such as moon face, acne, buffalo hump, diabetes, and striae (47.0% vs. 18.4%; P<0.001); more patients in the budesonide group achieved complete biochemical response (60.0% vs. 38.8%; P=0.001), and fewer experienced steroid-specific adverse effects (28.0% vs. 53.4%; P<0.001). At 12 months, 95 (54.8%) of 173 patients who completed part two of the study achieved complete response; rates of complete response were similar between patients originally randomized to budesonide or prednisone.

Comment: This study of well-characterized AIH showed that budesonide plus azathioprine was superior to prednisone plus azathioprine at inducing and maintaining remission with fewer steroid-specific adverse effects. Because the primary efficacy endpoint was determined at 6 months, the study did not address whether remission was maintained long term with budesonide. In addition, budesonide is considerably more expensive than prednisone and thus might not be cost-effective if needed long term. These issues aside, clinicians should consider budesonide plus azathioprine as another treatment option for AIH.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology December 17, 2010