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Size matters ▸
Liver biopsy has remained the “gold standard” to assess the severity of liver injury despite studies showing significant intra and interobserver variability in the evaluation of inflammation (grade) and fibrosis (stage). Serial biopsies have been used extensively to monitor the progress of disease and response to therapy.
Colloredo et al have highlighted yet another variable that affects the estimation of disease severity using liver biopsies. From patients with chronic hepatitis B and C, authors selected 161 liver biopsies, each ⩾3 cm long and 1.4 mm wide, and used the “Ishak scale” to assess the severity of disease. The biopsies were then made shorter (by covering with opaque paper) and/or thinner (by viewing through a modified micrometer eyepiece) and blindly re-read by the same pathologist. As the biopsies shortened, more were graded as having mild disease (50% in ⩾3 cm, 60% in 1.5 cm, and 87% in 1 cm specimens; p<0.001). Cases staged as having mild fibrosis increased in the shorter specimens (59% in ⩾3 cm, 68% in 1.5 cm, and 80% in 1 cm specimens; p<0.001). Both grade and stage were underscored in thinner samples regardless of their length.
In a way, this study has demonstrated the obvious, in that the size of the biopsy strongly influences the reporting of the severity of disease. The authors discourage the use of fine needle biopsies for this purpose. But, the implications extend beyond the issues of needle size and staging chronic hepatitis. The search for serum markers or imaging modalities that could reliably assess the severity and progress of liver injury should intensify.
The cause of oesophageal adenocarcinoma: the burning issue ▸
suggested reflux symptoms were a major risk factor for oesophageal adenocarcinoma. This seminal observation has had an important impact on the understanding of the aetiology of oesophageal adenocarcinoma but further studies are needed to support these findings. Wu et al report the results of a US case control study of 222 oesophageal, 277 gastric cardia, and 443 distal gastric adenocarcinoma patients compared with 1356 age and sex matched population controls. Reflux symptoms were strongly associated with the risk of oesophageal adenocarcinoma with a weaker association with gastric cardia adenocarcinoma. The adjusted odds ratio for patients with oesophageal adenocarcinoma having weekly heartburn was 3.16 (95% confidence interval (CI) 2.00–5.01) and if reflux symptoms had been present for more than 15 years the adjusted odds ratio was 4.89 (95% CI 3.18–7.53). These findings are less dramatic than the previous case control study (Lagergren et al reported an adjusted odds ratio of 7.7 (95% CI 5.3–11.4) for weekly reflux symptoms in oesophageal adenocarcinoma patients, and if symptoms were present for >20 years the odds ratio was 16.4 (95% CI 8.3–28.4)). Nevertheless, these data are important as they add support to the hypothesis that reflux is a major cause of this fast increasing cancer.
Light at the end of the tunnel ▸
Management of patients with Barrett’s oesophagus (CLO) and high grade dysplasia (HGD) or early carcinoma is difficult. Photodynamic therapy (PDT) is appealing but many questions remain. The authors present their five year follow up data.
A total of 103 patients (aged 33–83 years), unfit for surgery, underwent 1–3 sessions of porfimer PDT, followed by Nd:YAG laser to residual areas of CLO, and long term proton pump inhibitor therapy: 14 had low grade dysplasia (LGD), 80 HGD, and nine had early stage carcinoma. The primary end point was elimination of dysplasia or cancer while treatment failure was defined as persistence of dysplasia or any grade of progression.
At a mean follow up of 51 months, treatment success rates were 92.9%, 77.5%, and 44.4% for LGD, HGD, and early cancer, respectively. All Barrett’s mucosa (albeit with additional laser therapy) was eliminated in 68%. Three patients developed subsquamous carcinoma and 30% overall had strictures as a result of PDT.
Impressive data indeed, but the study was unable to answer the key question of whether PDT can reduce the incidence of cancer in Barrett’s as this was not a randomised trial. From available literature, however, up to 25–50% of HGD patients might develop cancer over a five year period but accurate incidence rates for cancer in Barrett’s are lacking. These results are therefore welcome and promising but perhaps all we can say for now is that there may be light at the end of the tunnel.
Stemming the tide of refractory IBD ▸
Patients with acute or chronic myeloid leukaemia and inflammatory bowel disease (IBD) who undergo stem cell transplantation (SCT) appear to achieve extended remission of their IBD. The practical and ethical issues have been discussed (
. This report from four German centres describes the outcome in seven patients with Crohn’s and four with ulcerative colitis, all of whom had allogeneic SCT for chronic or acute myeloid leukaemia, or myelodysplastic syndrome. Myeloablative therapy with total body irradiation and cyclophosphamide or antithymocyte globulin was followed by transplantation of peripheral blood stems cells (n = 4), unmodified bone marrow (n = 4), or T cell depleted peripheral blood stem cells (n = 3). Eight had HLA identical sibling donors. Post-transplant immunosuppression with cyclosporin/methotrexate was augmented by methylprednisolone for acute graft versus host disease (8/11). IBD activity before transplant was rated quiescent (n = 5) or low (n = 6). Three of seven patients with Crohn’s had enterocutaneous fistulae. Ten of 11 survived transplant (one died of fungal pneumonia after 10 months). Median follow up was 34 (range 3–117) months after transplant. One with ulcerative colitis and one with Crohn’s developed mild symptoms after transplant, but colonoscopy and histology were not typical of colitis or Crohn’s. Two patients were able to stop immunosuppression.
It is a leap of faith to apply SCT to patients with Crohn’s or ulcerative colitis who do not have a haematological malignancy. Nevertheless, an early report of autologous SCT in six patients with severe refractory Crohn’s disease was guardedly optimistic (
). One hopes that one of the many new biological therapies for Crohn’s and ulcerative colitis will offer other ways of turning the tide.
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