Karen Geboes

Erosive enterocolitis in mycophenolate mofetil-treated renal-transplant recipients with persistent afebrile diarrhea.

Background. Diarrhea is the most frequently reported adverse event in mycophenolate mofetil (MMF)-treated transplant patients. The aim of this study was to explore the gastrointestinal tract in MMF-treated renal transplant recipients with persistent afebrile diarrhea to characterize its nature and etiology. Methods. Renal transplant recipients with persistent afebrile diarrhea (daily fecal output >200 g) were prospectively investigated for infections, morphologic, and functional (gastrointestinal motility and intestinal absorptive capacity) integrity of the gastrointestinal tract; 26 patients met the inclusion criteria. Results. All but one patient had an erosive enterocolitis. Seventy percent of the patients had malabsorption of nutrients, contributing to the diarrhea. In ±60%, an infectious origin was demonstrated and successfully treated with antimicrobial agents without changes in immunosuppressive regimen. In ±40%, no infection occurred, but a Crohn’s disease-like pattern of inflammation was noted. These patients also had a less pronounced bile-acid malabsorption but a significant faster colonic transit time, correlating with the trough level of mycophenolic acid (MPA). Cessation of MMF, however, was associated with allograft rejection in one third of these patients. Conclusions. Persistent afebrile diarrhea in renal transplant recipients is characterized by erosive enterocolitis, which is of infectious origin in ±60%. In ±40%, a Crohn’s disease-like (entero-)colitis was present. Because reduction or cessation of MMF was the only effective therapy, MPA or one of its metabolites may be suggested as a possible cause. However, reduction or cessation of MMF was associated with an increased risk for rejection.

The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon

In the present study, the production and fate of bacterial metabolites in the colon were investigated in a direct way using two substrates labelled with stable isotopes: lactose [(15)N,(15)N]ureide as a source of labelled ammonia and egg proteins intrinsically labelled with [(2)H4]tyrosine as a precursor of [(2)H4]p-cresol. Both ammonia and phenolic compounds are believed to be carcinogenic. Stimulation of carbohydrate fermentation in order to prevent accumulation of these toxic metabolites was induced by inclusion of inulin in a test meal or by addition of inulin to the daily diet, allowing us to distinguish between changes induced by the actual presence of a fermentable carbohydrate and effects caused by a long-term dietary intervention. When a single dose of inulin was administered together with the labelled substrates, a significant increase in faecal (15)N excretion, accompanied by a proportional decrease in urinary (15)N excretion was observed, probably reflecting an enhanced uptake of ammonia for bacterial biosynthesis, since an increased concentration of labelled N in bacterial pellets was found. A statistically significant reduction of urinary [(2)H4]p-cresol excretion was also noted. Upon supplementation of inulin to the daily diet during 4 weeks, however, only a tendency towards decreased urinary excretion of both labelled and unlabelled p-cresol was noted. Further studies are warranted to confirm these results in a larger cohort.

Inulin is an ideal substrate for a hydrogen breath test to measure the orocaecal transit time.

Background : A better substrate is needed for a hydrogen breath test to measure the orocaecal transit time. The currently used substrate, lactulose, accelerates the orocaecal transit time by increasing the osmolality of the gut contents. The recently developed lactose 13C‐ureide breath test is reliable, but a hydrogen breath test is preferred, as it allows the simultaneous investigation of the digestion and absorption of nutrients by means of 13C‐labelled compounds.

Practical and Molecular Evaluation of Colorectal Cancer: New Roles for the Pathologist in the Era of Targeted Therapy

CONTEXT Colorectal cancer is the third most common cancer and the fourth most common cause of cancer death worldwide. Patient cases are discussed in multidisciplinary meetings to decide on the best management on an individual basis. Until recently, the main task of the pathologist in such teams was to provide clinically useful reports comprising staging of colorectal cancer in surgical specimens. The advent of total mesorectal excision and the application of anti-epidermal growth factor receptor (EGFR)-targeted therapies for selected patients with metastasized colorectal cancer have changed the role of the pathologist. OBJECTIVES To present the traditional role of the pathologist in the multidisciplinary team treating patients with colorectal cancer, to address the technique of total mesorectal excision and its implications for the evaluation of surgical specimens, to offer background information on the various EGFR-targeted therapies, and to review the currently investigated tissue biomarkers assumed to be predictive for efficacy of such therapies, with a focus on the role of the pathologist in determining the status of such biomarkers in individual tumors. DATA SOURCES This article is based on selected articles pertaining to biopsy evaluation of colorectal carcinoma and reviews of EGFR-targeted therapies for this cancer. All references are accessible via the PubMed database (US National Library of Medicine and the National Institutes of Health). CONCLUSIONS Pathologists play an increasingly important role in the diagnosis and management of colorectal cancer because of the advent of new surgical techniques and of targeted therapies. It is expected that this role will increase further in the near future.

Endoscopy and Histopathology

Endoscopy and histopathology are two morphological diagnostic procedures which allow direct examination of organs with optical methods. They can detect abnormalities of the normal anatomy and histology and provide a precise diagnosis. Based on the information derived from these investigations an adequate treatment, either medical or surgical can be proposed. The optical resolution of both methods is different. Classical endoscopy is using essentially the naked eye observation of the tissue which allows a diagnosis of an ulcer or a raised lesion for instance, while histopathology is reaching the cellular and sub-cellular level. The new endoscopic techniques however do increase the optical resolution. The major contributions of histopathology to endoscopy are situated in inflammatory and neoplastic diseases. Histopathology allows a more precise diagnosis of the type of inflammation and a better classification of tumours. This has again an impact upon treatment. For the diagnosis, histopathology can be an essential element, as illustrated by gluten sensitive enteropathy (although serology is also an essential element) or by identification of specific pathogens such as Giardia lamblia, Mycobacterium avium, cryptosporidia.... Histopathology can further be important for the confirmation of a diagnosis but very often it will provide a more precise diagnosis by determining the aetiology of inflammation as illustrated by autoimmune gastritis, or by typing a tumour (adenocarcinoma or lymphoma). In addition, histopathology can provide essential elements for further therapy strategy by demonstrating the presence or absence of risk factors for residual tumour in polypectomy or endoscopic mucosal resection. Indirectly, it offers the possibility of using additional techniques such as biomarkers for dysplasia and cancer or the demonstration of mutations such as KRAS in colorectal cancer or HER2 amplification in oesophageal and gastric cancer.[1, 2].These applications can have important therapeutic consequences. It has been shown for instance that activating mutations of the KRAS gene are associated with poor response to anti-EGFR therapies and that patients