CORRELATIONS BETWEEN VIDEO CAPSULE ENDOSCOPIC FINDINGS AND CLINICAL ACTIVITY IN CROHN’S DISEASE

Background and Aims: Video capsule endoscopy (VCE) has become increasingly important as a simple method for observing the entire small intestine. The indications for VCE are obscure gastrointestinal bleeding and investigation of Crohn’s disease (CD). However, the correlation between endoscopic findings obtained by VCE and clinical findings in known cases of CD is not clear, and we therefore investigated this in the present study. Patients and methods: In 30 patients with known CD (Crohn’s disease activity index [CDAI] 0–420; median = 158.3), double contrast enteroclysis (ENT) was performed 1–3 weeks prior to VCE. The relationship between the VCE findings and hematological analysis/CDAI was examined. Results: In 17 of 30 patients, the entire small intestine could be investigated by VCE, whereas in the remaining 13 patients the terminal ileum could not be investigated. The following exhibited positive correlations: total lesions and CDAI (correlation coefficient values: r_s = 0.661, adjusted P < 0.0061), ulcers and C‐reactive protein (CRP) (r_s = 0.607, adjusted P < 0.0061), total lesions and CRP (r_s = 0.604, adjusted P < 0.0061). Conclusions: Analysis with VCE suggests that CDAI and CRP indicate the activity of intestinal lesions in patients with known CD, and that CRP, in particular, is associated with the activity of ulcerative lesions of the intestine. This may contribute to revised guidelines for VCE in the future.     

A trip through the signaling pathways of melanoma

Many cellular signaling pathways are involved in the development of cancer. Depending on the tumor entity, the nature as well as the mode of activation can differ. Some signaling pathways frequently show changes as all tumor cells have to fulfill some basic requirements such as independence from growth factors or insensitivity against apoptosis. In this review, the possibilities of a tumor to manipulate signaling pathways to reach these goals are exemplified based on an archetypical melanoma cell. In addition, new therapeutic options based on the knowledge of signaling pathways will be discussed.     

HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR‐SSP, and measurement of anti‐TPO, free thyroxine and thyroidstimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti‐TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*. The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS. The presence of anti‐TPO antibodies strongly suggests autoimmune thyroiditis. There is intra‐familial association between the haplotype HLA‐B*15 ‐DRB1*04 ‐DRB4* and anti‐TPO,emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.     

LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study.

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.     

Prospect of Endoscopic Mucosal Resection for Early Gastric Cancer: Our Devices in Insulated‐Tip Electrosurgical Knife Method

In Kobe University Hospital, a new method for endoscopic mucosal resection (EMR) using insulated‐tip electrosurgical knife (IT‐EMR) for early gastric cancer (EGC) was introduced from November 2001. To achieve an effective and safe IT‐EMR procedure, we use a high‐frequency surgical unit for cutting and coagulation (ERBOTOM ICC 200) with automatically controlled cutting mode (ENDOCUT). In this study, we show not only our results of IT‐EMR for EGC in comparison with those of the conventional strip biopsy method, but also the optimal conditions for the apparatus of a high‐frequency surgical unit to prevent complications such as bleeding and perforation.     

IMPROVED BALLOON‐TIPPED TRANS‐ANAL ILEUS TUBE

Background: For management of bowel obstruction due to colorectal cancer, endoscopic trans‐anal decompression technique has been first reported by Lelcuk et al. in 1986 using balloon dilatation technique. Since then, various types of trans‐anal decompression tubes have been clinically used for patients suffering from left side obstructing colorectal cancer as an emergent decompressing device. At present, two types of trans‐anal ileus tube (trans‐anal decompression tube) have been available for clinical use, but they have two main problems that are late colon perforations caused by the tip of the tube and tube obstruction by stool. Methods: Analysis on three late colon perforations experienced with the use of conventional devices drew possible improvements to make a trans‐anal ileus tube less harmful. To overcome the pitfalls inherent to conventional tubes, the author has developed an improved trans‐anal ileus tube with a balloon installed at the very end of the tube (‘balloon‐tipped type’) made of silicone, measuring 1200 or 1700 mm in total length and 22 Fr in outer diameter. It has been used for 12 cases with obstructing colorectal cancer etc. and its outcomes were compared with those obtained by the use of conventional trans‐anal ileus tube. Results: No late perforations have been encountered, but tube obstruction did occur in one of 12 cases. Conclusion: The new trans‐anal ileus tube with a balloon installed at the tip of ileus tube is considered to be safer and especially effective in preventing late colon perforation and tube obstruction.     

NEW DEVICE TO PERFORM COAGULATION AND IRRIGATION SIMULTANEOUSLY DURING ENDOSCOPIC SUBMUCOSAL DISSECTION USING AN INSULATION‐TIPPED ELECTROSURGICAL KNIFE

Background: Although bleeding is an unavoidable complication of endoscopic submucosal dissection (ESD), endoscopic hemostasis using an insulation‐tipped electrosurgical knife (IT) knife is impossible because an insulator is mounted at the tip of the knife. We have developed a new type of hood which could perform both coagulation and irrigation simultaneously. Methods: Our new device was fabricated by drilling a side hole in the cap portion of a conventional transparent hood followed by attaching a machined papillotomy knife to the exterior surface of the hole. Results: Our new hood was useful for hemorrhage during ESD using IT knife. Conclusions: With this method, endoscopic hemostasis using IT knife is easy, as hemostatic procedure can be performed under irrigation and coagulation using conventional endoscopy.     

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.     

Effect of UVB 311 nm irradiation on normal human skin

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1⁺ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a⁺ cells and a moderate increase of HLA-DR⁺ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1⁺ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.