Advanced diffusion MRI provides evidence for altered axonal microstructure and gradual peritumoral infiltration in GBM in comparison to brain metastases.

PURPOSE: In contrast to peritumoral edema in metastases, GBM is histopathologically characterized by infiltrating tumor cells within the T2 signal alterations. We hypothesized that depending on the distance from the outline of the contrast-enhancing tumor we might reveal imaging evidence of gradual peritumoral infiltration in GBM and predominantly vasogenic edema around metastases. We thus investigated the gradual change of advanced diffusion metrics with the peritumoral zone in metastases and GBM. METHODS: In 30 patients with GBM and 28 with brain metastases, peritumoral T2 hyperintensity was segmented in 33% partitions based on the total volume beginning at the enhancing tumor margin and divided into inner, middle and outer zones. Diffusion Tensor Imaging (DTI)-derived fractional anisotropy and mean diffusivity as well as Diffusion Microstructure Imaging (DMI)-based parameters Dax-intra, Dax-extra, V­CSF and V-intra were employed to assess group-wise differences between inner and outer zones as well as within-group gradients between the inner and outer zones. RESULTS: In metastases, fractional anisotropy and Dax-extra were significantly reduced in the inner zone compared to the outer zone (FA p = 0.01; Dax-extra p = 0.03). In GBM, we noted a reduced Dax-extra and significantly lower intraaxonal volume fraction (Dax-extra p = 0.008, V­intra p = 0.006) accompanied by elevated axial intraaxonal diffusivity in the inner zone (p = 0.035). Between-group comparison of the outer to the inner zones revealed significantly higher gradients in metastases over GBM for FA (p = 0.04) as well as the axial diffusivity in the intra- (p = 0.02) and extraaxonal compartment (p < 0.001). CONCLUSION: Our findings provide evidence of gradual alterations within the peritumoral zone of brain tumors. These are compatible with predominant (vasogenic) edema formation in metastases, whereas our findings in GBM are in line with an axonal destructive component in the immediate peritumoral area and evidence of tumor cell infiltration with accentuation in the tumor's vicinity.

[Cell depletion and myoablation for neuroimmunological diseases]. / Zelldepletion und Myeloablation bei neuroimmunologischen Erkrankungen.

BACKGROUND: The treatment of autoimmune disorders of the nervous system is based on interventions for the underlying immune phenomena. OBJECTIVE: To summarize concepts of cell depletion and myeloablation studied in the context of neuroimmunological disorders. METHOD: Evaluation of the available literature on multiple sclerosis as the most widely studied neuroimmunological entity. RESULTS: Three concepts have been introduced: classical immunosuppressants, such as azathioprine, mitoxantrone and cyclophosphamide exert general lymphopenic effects and thereby moderately decrease disease activity. Myeloablative regimens combined with autologous hematopoietic stem cell transplantation have a profound and in most cases long-lasting impact on autoimmunity at the cost of potentially life-threatening side effects. Alemtuzumab (anti-CD52), rituximab and ocrelizumab (both anti-CD20) are depleting antibodies directed against certain lymphocyte subsets and substantially ameliorate disease activity in relapsing-remitting multiple sclerosis. Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis. CONCLUSIONS: Most of the presented cell-depleting and myeloablative therapies are highly effective treatment options but are also accompanied by significant risks. In the context of the increasing number of alternative immunomodulatory options the indications for use should be cautiously considered.

A competitive enzyme-linked immunosorbent assay for quantification of tetrastatin in body fluids and tumor extracts.

Basement membrane collagens or derived fragments are measured in biological fluids such as blood and urine of patients and appear to be useful for diagnosis, prognostication, or treatment monitoring as proposed for endostatin, a fragment of collagen XVIII, or tumstatin, a fragment of collagen IV. Tetrastatin, the NC1 alpha 4 collagen IV domain, was previously reported to inhibit tumor growth and angiogenesis. The aim of this study was to develop and validate a method to measure tetrastatin concentrations in human fluids. We developed a competitive enzyme-linked immunosorbent assay (ELISA). It allowed measuring tetrastatin levels in human serum, bronchial aspiration and bronchoalveolar lavage fluids, and lung tissue extracts. The tetrastatin level was significantly higher in tumor tissues than in healthy lung tissues. Tetrastatin competitive ELISA could be useful to quantify tetrastatin in tissues and biological fluids for the diagnosis or prognostication of diseases in which basement membrane metabolism may be altered, especially tumor progression.

Identification of Raman spectroscopic markers for the characterization of normal and adenocarcinomatous colonic tissues.

Raman spectroscopy has been recognised as a valuable analytical tool in biological and medical research. This technique allows probing molecular vibrations of samples without external labels or extensive preparation. This non-destructive optical technique can provide rapid and objective and reproducible measurements of sample biochemistry and identify variations that occur between healthy and diseased tissues. In fact, biochemical changes within tissue may either initiate disease or occur as a result of the disease process. The qualitative analysis of such changes provides important clues in the search for a specific diagnosis and the quantitative analysis of biochemical abnormalities is important in measuring the extent of the disease process, designing therapy and evaluating the efficacy of treatment. In this paper, we discuss one medical application of near-infrared Raman microspectroscopic imaging as a diagnostic tool to investigate, ex vivo, the changes between normal and adenocarcinomatous human colonic tissues. Multivariate statistical analysis was applied on these measured data to identify the molecular composition and distribution of lipids, proteins, mucus and collagens in normal and malignant tissue. Unsupervised hierarchical cluster analysis shows two unsupervised distinct clusters that were assigned to normal and adenocarcinomatous in accordance with conventional histopathological examination. The spectral images allowed good correlation between pseudo-color Raman and histopathological features.

Increased risk of colonic neoplasia in patients with sporadic duodenal adenoma.

BACKGROUND: Recent studies have shown an increased risk of colorectal neoplasia in patients with duodenal neoplasia. The aim of this retrospective case-control study was to confirm this risk. PATIENTS AND METHODS: Rate of colorectal neoplasia in 29 patients with one or more duodenal adenomas were compared with controls matched for gender and age, but without duodenal adenomas (one case to two controls). Patients with neoplasia of the ampulla, familial adenomatous polyposis or other known hereditary conditions of the digestive tract were excluded. Indications for upper and lower gastrointestinal endoscopy in controls were abdominal pain or changes in bowel habits. Controls with anemia or digestive bleeding were not included. Neoplastic lesions found at colonoscopy were classified as adenomas, advanced adenomas (size > or =10 mm, villous component, high-grade dysplasia), cancers and advanced neoplasia (cancers and advanced adenomas). Comparison between groups was by Fisher's exact test or Student's t test. Odds-ratios (OR) and 95% confidence intervals were calculated, if the difference was significant. RESULTS: Mean age of the 29 cases (seven women, 22 men) was 63.2 years and that of the 58 controls (14 women, 44 men) was 62.5 years. First-degree family history of colorectal cancer was present in four cases (13.8%) and eight controls (13.8%) (NS). Colonoscopy showed at least one adenoma in 15 cases (51.7%) and 11 controls (19%) (P=0.0027; OR 1.87, 1.0-3.49), advanced adenomas in four cases (13.8%) and three controls (5.2%) (NS), and colonic adenocarcinoma in three cases (10.3%) and no controls (0%) (P=0.03). Advanced neoplasia was present in seven cases (24.1%) and three controls (5.2%) (P=0.014; OR 2.86, 0.96-8.52). Results were not significantly modified after the exclusion of patients with a family history of colorectal cancer. CONCLUSION: Although lacking in statistical power, these results confirm that patients with sporadic duodenal adenoma are at high risk of colonic adenoma and advanced neoplasia, warranting systematic colonoscopy.

Lumican inhibits B16F1 melanoma cell lung metastasis.

BACKGROUND: Lumican is a small leucine-rich proteoglycan (SLRP) of the extracellular matrix (ECM) involved in the control of melanoma growth and invasion. The aim of the present study was to analyse the role of lumican in the regulation of the development of lung metastasis. METHODS: B16F1 melanoma cells stably transfected with lumican expressing plasmid (Lum-B16F1) were injected to syngenic mice. The lung metastasis was compared to mice injected with mock-transfected B16F1 cells (Mock-B16F1). The expression of lumican, cyclin D1, apoptotic markers, vascular endothelium growth factor (VEGF) and Von Willebrand Factor (vWF) within lung metastasis nodules was investigated by immunohistochemistry. In parallel, cells cultured in presence of lumican were assayed for apoptosis and motility. RESULTS: We observed that the number and the size of lung metastasis nodules were significantly decreased in mice injected with Lum-B16F1 cells in comparison to Mock-B16F1 cells. This was associated with an increase of tumour cell apoptosis within metastasis nodules but the cell proliferation rate remained constant in the two mice groups. In contrast, the VEGF immunostaining and the number of blood vessels within the lung metastasis nodules were decreased in the lumican-expressing tumours. In vitro, a significant decrease of apoptotic markers in wild type B16F1 cells incubated with increasing amounts of lumican core protein was observed. In addition, pseudotubes formation on Matrigel(R) and the migratory capacity of endothelial cells was inhibited by lumican. Altogether, our results indicate that lumican decreases lung metastasis development not only by inducing tumour cell apoptosis but also by inhibiting angiogenesis.

[Endometriomas of the abdominal wall: Imaging findings]. / Endométriomes de la paroi abdominale: apport de l'imagerie.

Endometrioma of the abdominal wall is a not well-recognized disease and usually develops after pelvic surgery. The most common presentation is a mass of the abdominal wall associated with pain during menstruation. We report six cases of parietal endometriomas studied with ultrasonography, CT, and in one case with MRI. Our results are compared with recent findings in the literature. The purpose of this study was to describe the clinical and imaging findings in abdominal wall endometriomas that can help reach a presurgical diagnosis.

A prospective, randomized clinical study of adjunctive peripheral parenteral nutrition in adult subacute care patients.

BACKGROUND: A number of frail, older, undernourished patients cannot maintain adequate oral intake to meet protein-calorie needs after an illness, even when high-density nutritional supplements are added. Tolerance to enteral nutrition by gastric tube is poor in this group of patients. Peripheral parenteral nutrition is an effective method of administering nutritional support to patients with mild to moderate nutritional deficiencies who are unable to receive enteral nutrition or for whom enteral nutrition alone cannot meet energy needs. However, no data exists for the use of peripheral parenteral nutrition longer than two weeks and overall there are remarkably few studies on the efficacy of peripheral parenteral nutrition. METHODS: A Phase 4, single center, prospective, randomized, parallel group design clinical trial was conducted to evaluate long-term safety of peripheral parenteral nutrition in post-acute patients receiving inadequate enteral nutrition. Nutritional status was measured by the Mini-Nutritional Assessment and functional status by the Functional Inventory Measure. Subjects received a mean duration for peripheral parenteral nutrition of 15.8 +/- 6.7 days (range 8-23). RESULTS: The peripheral parenteral nutrition group demonstrated several trends towards improvement in prealbumin, CD4 cell count, and functional status compared to the untreated control group. Two patients in the peripheral parenteral nutrition group developed low-grade phlebitis; however, this did not result in discontinuing intravenous therapy. No other adverse events occurred. This study demonstrates that peripheral parenteral nutrition is feasible and safe in postacute care. CONCLUSIONS: We conclude that peripheral parenteral nutrition can be safely administered in post-acute settings with a low rate of complications.

[Microscopic vascular study of the colon with the corrosion casting technique]. / Etude vasculaire microscopique du colon par la technique d'injection-corrosion.

The aim of this study is, firstly, to assess the accuracy of vascular casts obtained at various times after death and secondly to describe the mucosal microvascular architecture of the cat colon. Two injections were realized, the first one on a non-embalmed human corpse, 12 days after the death, and the other one on a cat, immediately following euthanasia. Results show that this second cast seems finer and more detailed than the cast stemming from the human corpse; indeed, the finest vessels obtained are about 6 microns while they are about 15 microns on the human corpse. This could be explained by a post-mortem obstruction of microvessels, that prevented the passage of the injected product or by an insufficient amount of product injected. Finally, the vascular cast of the cat colic mucosa presents a regular honeycomb-like network that bounds the colonic mucosal glands, a finding consistent with the results reported previously.

[Laparoscopic diagnosis of stenosing eosinophilic jejuno-ileitis]. / Diagnostic coelioscopique d'une jéjuno-iléite sténosante à éosinophiles.

INTRODUCTION: Eosinophilic gastroenteritis of unknown origin could be isolated or integrated in idiopathic hypereosinophilic syndrome. Clinical expression is variable since the lesion may affect any area of the gastrointestinal tract and any layer of the wall. EXEGESIS: A 25-year-old male patient had digestive symptoms such as peritoneal, obstructive and diarrheal signs, associated with blood eosinophilia, giving evidence for eosinophilic jejuno-ileitis. Computer tomography revealed an extensive obstruction of the jejuno-ileum and thickening of the intestinal wall. The diagnosis was obtained using laparoscopy and controlled wedge biopsy, which showed a predominantly external infiltration of the intestinal wall by eosinophils. The disease evolution was favorable with corticosteroid therapy. CONCLUSION: Worrying and persistent digestive symptomatology, associated with blood eosinophilia, particularly when intestinal wall infiltration is revealed by computer tomography, should lead one to perform a laparoscopy to guide a surgical biopsy of the intestinal wall.

[Diclofenac-induced colitis complicated by Klebsiella oxytoca infection]. / Colite induite par le diclofénac et compliquée d'une infection à Klebsiella oxytoca.

A 25-year-old man presented with abdominal pain and bloody diarrhea. Colonoscopy showed hemorrhagic proctocolitis with superficial erosions. Histology was consistent with the diagnosis of ulcerative colitis and biopsy cultures were negative. Despite treatment with prednisolone (40 mg/day), his clinical condition deteriorated and he was referred to our institution. On repeated questioning, the patient reported self-medication with diclofenac (200 mg/day) for 6 weeks to treat tendinitis prior to the beginning of digestive symptoms. Rectosigmoidoscopy confirmed bleeding colitis and repeated biopsy cultures showed Klebsiella oxytoca. Corticosteroids were stopped and ofloxacin (400 mg/day) was prescribed for 14 days. Diarrhea quickly resolved. Colonoscopy 8 weeks later showed only patchy erythematous mucosa without bleeding or erosions. Two years later, the patient remains asymptomatic with normal total colonoscopy. The definitive diagnosis was de novo NSAID-induced colitis subsequently complicated by Klebsiella oxytoca infection.

[Protective effect of appendectomy on the development of ulcerative colitis. A case-control study]. / Effet protecteur de l'appendicectomie contre la rectocolite hémorragique.

AIMS: To examine by a case-control study the relationship between appendectomy and subsequent ulcerative colitis development in a French population. METHODS: A total of 150 patients with ulcerative colitis were matched for age (+/- 5 years) and sex, with 150 controls recruited in a preventive medicine center. The following data were collected from medical records and by standardised questionnaire in consultation or by phone: appendectomy and tonsillectomy before the onset of ulcerative colitis, smoking habits and area of residence. RESULTS: The rate of previous appendectomy in patients with ulcerative colitis was 8% (12/150) compared with 30.6% (46/150) in the control group (P=0.001). There was no significant association between ulcerative colitis and tonsillectomy (25.3 and 27.3% in the control and the ulcerative colitis groups, respectively). Smoking was more frequent in the control group (36%) than in the ulcerative colitis group (25.3%) but the difference was not significant (P=0.07). In multivariate analysis, the risk of developing ulcerative colitis was significantly lower after previous appendectomy (odds ratio=0.26; 95% confidence interval: 0.13-0.55; P=7 x 10(-4)). CONCLUSION: Our study confirms the inverse association between appendectomy and subsequent ulcerative colitis, in a French population, after adjusting on smoking.

Virological and histological responses to one year alpha-interferon-2a in hemodialyzed patients with chronic hepatitis C.

BACKGROUND: alpha-Interferon-2a (IFNalpha) alone is a therapy of limited proven benefit for non-uremic patients with chronic hepatitis C virus (HCV) infection. In dialyzed patients, such an effect is suggested on small short-term studies without sufficient clinical and virologic follow-up to document any sustained effect. PROTOCOL: Twelve chronically hemodialyzed patients with chronic hepatitis C and waiting for renal transplantation were included in a prospective open study of treatment with IFNalpha. We used, as did others, doses of 3 million units (MU), three times a week, but for a longer period of treatment of 12 months. Follow-up was continued for 6 months after the end of IFNalpha in order to document any sustained biochemical, virological and histological responses. RESULTS: Aminotransferase levels returned to the normal range within 1-2 months of treatment in all patients in whom they had been elevated at baseline. At 1 month of treatment, serum HCV-RNA was not detected in 5 (41%) patients and in 9 (75%) at 12 months. A sustained virological response was documented in 4 (33%) patients 6 months after the end of treatment. Relapse occurred in 5 patients within 2 months after IFNalpha withdrawal. HCV genotype was not predictive of any sustained response. At inclusion, using the histologic Metavir scoring system, half of the patients had low-grade cytolytic activity and none had cirrhosis. After IFNalpha, liver biopsy specimens were available from 9 patients and showed histologic improvement in 3. IFNalpha tolerance was poor, inducing a 5% mean weight loss and the acute rejection of two nonfunctioning kidney grafts. CONCLUSION: This study documents that administration of IFNalpha at 3 MU three times a week, for 12 months, in hemodialysis patients with chronic hepatitis C was efficient for clearing the serum of HCV-RNA in 75% of the patients. A sustained response was maintained in one third of these patients after cessation of IFNalpha, and was predicted by the early serum clearance of the virus within the first 2 months of treatment. We confirm that a 12-month treatment period carries a higher sustained response rate than shorter treatment periods. These encouraging results call for larger studies in uremic patients, using IFNalpha alone or in association with new antiviral drugs.