bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological and Molecular Aspects of Gastroenteropancreatic Neuroendocrine Tumors
Authors: Rindi G. , Villanacci V. , Ubiali A.
Published: April 2003

Neuroendocrine tumors of the digestive tract are rare entities characterized by significant phenotype differences and traditionally considered to originate from cells of the diffuse endocrine system of the pancreas and gut. Two major categories with significant phenotype and clinical behavior differences are identified as well-differentiated and poorly differentiated tumors. Investigation on the molecular basis of tumor development points to an important role for the multiple endocrine neoplasia syndrome type-1 (MEN1) gene because of its frequent abnormality observed both in well-differentiated and poorly differentiated tumors. Other genes are possibly involved, though the available data need support from studies on larger series of tumors.
Endoscopic Ultrasonography of Neuroendocrine Tumours
Authors: Zimmer T. , Scherübl H. , Faiss S. , Stölzel U. , Riecken E.-O. , Wiedenmann B.
Published: April 2003

Neuroendocrine tumours (NETs) of the upper gastrointestinal tract are mainly located in the pancreas, stomach or duodenum. The aims of preoperative work-up are the localization of primary tumour(s), determination of local tumour invasion, of lymph node metastases and of the hormones secreted by the tumour. Endoscopic ultrasonography (EUS) offers ideal conditions to localize and stage NETs of the foregut. We report our results in localizing and staging NETs of the foregut in 40 patients examined between 1990 and 1997 by EUS, somatostatin receptor scintigraphy (SRS), computed tomography (CT), magnetic resonance imaging (MRI) and transabdominal ultrasound (US). EUS shows the highest sensitivity in localizing insulinomas compared with SRS, US, CT and MRI. US and EUS should be the first-line diagnostics if insulinoma has been proven by a fasting test. Further diagnostic procedures are unnecessary in most cases. Further diagnostics such as CT or MRI to search for distant metastases are necessary in large tumours or local invasive tumours. EUS shows the highest accuracy to detect or exclude pancreatic gastrinomas, but fails to detect extrapancreatic gastrinomas in about 50%. The combination of EUS and SRS gives additional information. First-line diagnostics in gastrinoma patients should be SRS and CT or MRI. If no metastases are detected, EUS should be the next preoperative imaging procedure. In nonfunctional NETs, EUS provides the best information on local tumor invasion and regional lymph node involvement.
Treatment of Neuroendocrine GEP Tumours with Somatostatin Analogues
Authors: Arnold R. , Simon B. , Wied M.
Published: April 2003

Background: Somatostatin and its long-acting analogues are effective in symptom control in patients with functionally active neuroendocrine GEP tumours. Several in vitro and in vivo reports suggest that they are also able to control tumour growth. Methods: Critical review of published data on the effect of long-acting somatostatin analogues on symptom and growth control in patients with metastatic neuroendocrine GEP tumours. Results: With the exception of insulinoma and gastrinoma, octreotide acetate and other long-acting somatostatin formulations are currently the therapeutic principle of first choice to control hormone-mediated symptoms. The consequences of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome are best controlled by proton pump inhibitors. Available data on growth control indicate that stabilization of tumour growth seems to be the most beneficial antiproliferative effect occurring in up to 50% of patients. This effect is limited. However, it is unknown which tumour entity responds best to long- acting somatostatin analogues. Conclusion: Additional studies in patients with known spontaneous tumour growth and avoiding a mix-up of different entities of neuroendocrine malignancies are necessary to identify subpopulations of neuroendocrine tumours which respond to long-acting somatostatin analogues in terms of longer lasting growth inhibition.
Healing of Lymphocytic Gastritis by Eradication of Helicobacter pylori
Authors: Müller H. , Volkholz H. , Stolte M.
Published: April 2003

Background: It is not yet clear whether lymphocytic gastritis might not be a sequela of Helicobacter pylori  (Hp) infection. The aim of the present pilot study was, therefore, to investigate whether lymphocytic gastritis can be cured by Hp eradication, which, if affirmed, would provide indirect evidence for an etiopathogenic relationship. Patients and Methods: 98 of 220 patients with lymphocytic gastritis diagnosed between 1988 and 1998 were investigated at least twice, with 61 of them undergoing Hp eradication treatment. In 29 of these patients, the pretreatment histological work-up using the Warthin-Starry silver stain revealed Hp colonisation, while in the remaining 32 patients the biopsies from the antrum and corpus were negative for Hp. The other 37 patients received no treatment, and served as a control group. Results: Both in the group with Hp-positive, and in the group with Hp-negative histology prior to treatment, eradication treatment led to healing of the gastritis, i.e. to regression of the gastritis parameters including normalisation of the intra-epithelial lymphocyte count, in 93.1% and 84.3% of the cases, respectively. In the control group the histological findings did not change. Conclusions: The results of our retrospective study support the notion that most cases of lymphocytic gastritis might be a consequence of Hp infection. This, however, needs to be clarified definitively by a prospective, randomized, double-blind study.
Gastric Electrical Activity and Gastrointestinal Hormones in Dyspeptic Patients
Authors: Riezzo Giuseppe , Chiloiro Marisa , Russo Francesco , Clemente Caterina , Di Matteo Giovanni , Guerra Vito , Di Leo Alfredo
Published: April 2003

Aims: To explore the patterns of gastric electrical activity, gastric emptying and gastrointestinal hormones in dyspeptic patients and relate them to Helicobacter pylori status. Methods: Twenty-two patients with functional dyspepsia and 29 healthy volunteers underwent cutaneous electrogastrography and dynamic ultrasound before and after a test meal. All dyspeptic patients underwent endoscopy and biopsy; all subjects were examined for the presence of antibodies to H. pylori, and the plasma levels of gastrin, neurotensin, cholecystokinin, and pancreatic polypeptide were measured. Results: The area under the curve (AUC) of the normal slow wave percentage was lower in dyspeptic patients than controls (Kruskal-Wallis p = 0.016; Dunn’s test: H. pylori-positive patients: 21,235.5 [19,101.0–22,688.8] vs. H. pylori-negative controls: 22,532.0 [20,133.0–23,755.0], p < 0.05). The AUC of the tachygastria percentage was higher in dyspeptic patients than controls (p = 0.0001; H. pylori-positive patients: 2,173.5 [325.8–3,055.3] vs. H. pylori-negative controls: 682.0 [118.5–1,902.4], p < 0.05; H. pylori-negative patients: 1,843.0 [1,107.0–4,277.0] vs. H. pylori-negative controls: 682.0 [118.5–1,902.4], p < 0.05). The AUC of gastrin was higher in H. pylori-positive than H. pylori-negative subjects (p = 0.0002; H. pylori-positive patients: 16,146.5 [11,368.8–33,141.7] vs. H. pylori-negative controls: 11,250.0 [5,674.0–17,448.0], p < 0.05; H. pylori-positive controls: 20,250.0 [12,070.0–64,430.0] vs. H. pylori-negative controls: 11,250.0 [5,674.0–17,448.0], p < 0.05). In the total group of dyspeptic patients and in the H. pylori-positive patients, a negative correlation was found between the AUC of neurotensin and the total score for postprandial fullness (dyspeptic patients r = –0.51, p = 0.01; H. pylori-positive patients r = –0.66, p = 0.02). Conclusions: In dyspeptic patients, alterations in gastric electrical activity were not related to H. pylori infection. Nevertheless, H. pylori infection induces higher gastrin levels in both patients and asymptomatic subjects.
Reversal of the Gastric Effects of Nicotine by Nitric Oxide Donor Treatment
Authors: Ma J.J. , Hou D.Q. , Zhang Q.B. , Korsten M.A.
Published: April 2003

Nicotine intensifies experimental gastric ulceration by reducing gastric mucosal blood flow (GMBF) and mucus. As both these parameters can be improved by nitric oxide (NO), we evaluated the impact of a NO donor in ethanol-induced gastric mucosal injury in rats administered nicotine. A nicotine solution or water was administered for 20 days to Sprague-Dawley rats. NO donor (isosorbide dinitrate) was given 60 and 10 min before preparation of ex vivo gastric chambers and exposure to ethanol. Chronic nicotine intake significantly reduced GMBF and gastric mucus content. Nicotine intensifies ethanol-induced gastric injury and short-term administration of NO donor failed to antagonize the ulcerogenic action from either nicotine or alcohol. In another study, rats drank nicotine solution for 20 days, after which the nicotine was withdrawn and replaced by water for 10 additional days. NO donor was provided during these last 10 days. The gastric effects of nicotine persisted for at least 10 days after nicotine was withdrawn but then these effects could be abolished by prolonged NO treatment. Nicotine reduces plasma nitrite level, but gastric mucosal MPO activity remained unchanged. Our data suggest that nicotine cessation plus a longer period of NO donor administration can completely abolish the gastric effects of nicotine.
Food-Related Gastrointestinal Symptoms in the Irritable Bowel Syndrome
Authors: Simrén Magnus , Månsson Agneta , Langkilde Anna Maria , Svedlund Jan , Abrahamsson Hasse , Bengtsson Ulf , Björnsson Einar S.
Published: April 2003

Background/Aims: Postprandial symptoms are common in patients with irritable bowel syndrome (IBS). However, existing studies have come to different conclusions about the role of food in the pathophysiology of IBS. We explored the prevalence of subjective food-related gastrointestinal (GI) symptoms and its relationship to clinical characteristics and psychological factors in IBS. Methods: 330 patients with IBS and 80 healthy volunteers completed a food questionnaire developed for this study. The subjects graded their subjective symptoms after 35 different foods and a food score was obtained by adding the item scores. The relationship between subjective food-related GI symptoms and referral status, IBS subgroup (predominant bowel pattern), sex, anxiety, depression and body mass index (BMI) was estimated. Results: In 209 (63%) of the patients the GI symptoms were related to meals. Gas problems and abdominal pain were the most frequently reported symptoms. Foods rich in carbohydrates, as well as fatty food, coffee, alcohol and hot spices were most frequently reported to cause symptoms. The food score was higher in patients than in controls (p < 0.0001). In the IBS group higher scores were observed in patients with anxiety (p = 0.005), and females (p < 0.001), but the results were unrelated to IBS subgroup, referral status or BMI. The BMI did not differ between groups. Conclusion: A majority of IBS patients consider their symptoms to be related to meals. Especially foods rich in carbohydrates and fat cause problems. Nevertheless, the majority of IBS patients are normal or overweight. Female sex and anxiety predict a high degree of food-related symptoms in IBS.
High Correlation between Results of the [1-13C]-Phenylalanine Breath Test and Phenylalanine Hydroxylase (EC 1.14.16.1) Activity of the Liver in Rats
Authors: Ito Asuka , Kohno Tadashi , Hosoi Isaburo , Ohshima Junko , Ishii Yukimoto , Asai Satoshi , Ishikawa Koichi , Shibata Kunihiko
Published: April 2003

Background:13CO2 is decreased in patients with end-stage liver disease by the [1-13C]-phenylalanine breath test. Decreased 13CO2 is supposed to be caused by the decreased ability of the liver to oxidize phenylalanine. However, no direct evidence has been reported. Methods: The [1-13C]-phenylalanine breath test was performed in galactosamine hepatitis rats (n = 14) and control rats (n = 8). Plasma phenylalanine concentration before intravenous administration of [1-13C]-phenylalanine, the elimination rate of phenylalanine and the phenylalanine hydroxylase (PAH; EC 1.14.16.1) activity of the whole liver were examined. Results: Increase of 13CO2 in the breath [Δ13CO2 (‰)] of galactosamine hepatitis rats 2 min after administration of [1-13C]-phenylalanine was only 1/5 of that in control rats. The concentration of plasma phenylalanine and the elimination rate of plasma phenylalanine in hepatitis rats did not show significant differences compared to control rats. On the other hand, a clear difference in the activity of PAH was observed between hepatitis rats and control rats. Δ13CO2 (‰) 2 min after administration of [1-13C]-phenylalanine was highly correlated to the PAH activity of the whole liver (r = 0.917). Conclusion: It was strongly indicated that decreased Δ13CO2  in hepatitis rats was the result of decreased activity of PAH.
Severe Life-Threatening Diarrhea Caused by Azathioprine but Not by 6-Mercaptopurine
Authors: Marbet U. , Schmid I.
Published: April 2003

Azathioprine and its active metabolite 6-mercaptopurine are of increasing importance in the treatment of chronic inflammatory bowel disease. Most of the toxicity and the side effects of the medications are well known. However, it is relatively unknown that azathioprine toxicity itself can produce devastating diarrhea in patients with inflammatory bowel disease. This leads to great difficulties in differential diagnosis. We describe 2 patients with severe intestinal toxicity. This was life-threatening in 1 patient after reintroducing the drug. We therefore believe that any rechallenge with azathioprine should be only undertaken in a controlled hospital environment when a reaction to azathioprine is suspected. In addition, we found that this devastating intestinal toxicity did not reoccur after rechallenge with its active metabolite 6-mercaptopurine. Azathioprine and 6-mercaptopurine therefore cannot be used interchangeably.
Effects of Intraduodenal Bile on Interdigestive Gastrointestinal and Gallbladder Motility in Healthy Subjects
Authors: Luiking Y.C. , Kloppers N.J.M. , Roelofs J.M.M. , Nieuwenhuijs V.B. , Peeters T.L. , Akkermans L.M.A. , van Berge Henegouwen G.P.
Published: April 2003

Background/Aims: The enterohepatic circulation of bile acids is related to normal inter-digestive gastrointestinal motility, with the gut peptide motilin also being involved. This study aimed to investigate the effect of intraduodenal artificial bile infusion on antroduodenal and gallbladder motility so as to further elucidate the controlling factors. Methods: Twelve fasting, healthy male volunteers received artificial bile (80 mol% bile acids; 15 mol% phospholipids; 5 mol% cholesterol) or placebo (saline) intraduodenally for 10 min starting 30 min after the end of phase III, according to a double-blind, randomised, cross-over design. Antroduodenal motility, gallbladder volumes, and plasma motilin levels were measured. All values are means ± SEM. Results: The interval between infusion and the subsequent phase III, as well as the origin of this phase III were not significantly different between bile and saline. Antral pressure waves were significantly more frequent during and immediately after bile infusion compared with saline infusion (p < 0.05). The duration of phase I following infusion was significantly longer after bile (24.8 ± 3.7 min) than after saline infusion (13.1 ± 1.7 min; p < 0.05). The mean gallbladder volume tended to increase in the hours following bile infusion, but to decrease after saline infusion (p = 0.06). Plasma motilin increased after bile and saline infusion in an almost identical way. Conclusion: This study provides no clear evidence for a role of intraduodenal artificial bile (i.e. its main constituents) in the regulation of migrating motor complex cycling or feedback inhibition of inter-digestive gallbladder emptying.
Factor XIII Improves Gastric Stress Lesions in Rats
Authors: D’Argenio Giuseppe , Iovino Paola , Cosenza Vittorio , Della Valle Nicola , De Ritis Francesca , Mazzacca Gabriele
Published: April 2003

Background/Aims: Tissue transglutaminase has been reported to be involved in the healing of experimental gastric ulcer; nevertheless, other type(s) of transglutaminase could be involved. The present experiments aimed at examining whether plasma transglutaminase (factor XIIIa) contributes to such healing and at evaluating whether factor XIII supplementation improves gastric mucosal lesions. Methods: The healing effect of 200 U/kg of factor XIII administered intravenously was examined using a water immersion restraint rat model of stress gastric damage. The rats were sacrified 0, 2, 4, and 12 h after stress. The gastric mucosa was examined macroscopically and microscopically, and the transglutaminase activities were assayed in serum and gastric mucosa. Factor XIIIa and tissue transglutaminase protein levels in the gastric mucosa were analyzed by immunoblot. Immunohistochemistry was used to identify the location of tissue transglutaminase, factor XIIIa, and fibronectin in the gastric mucosa. Results: The transglutaminase activity, reduced by stress in the gastric mucosa, increased up to 12 h after stress, peaking at 4 h, when the ulcer index significantly decreased. The serum transglutaminase level was low at all time points. Exogenous administration of factor XIII allowed a faster reduction of the ulcer index that was coincident with an increased transglutaminase activity in the mucosa. Both tissue transglutaminase and factor XIIIa protein levels were reduced by 6 h of stress and increased after factor XIII administration. Immunohistochemistry showed a colocalization of both factor XIIIa and tissue transglutaminase with fibronectin in the extracellular matrix of the damaged area. Conclusions: Two forms of transglutaminase are involved in the healing of stress-induced gastric erosions, and factor XIII administration allows faster gastric mucosa healing.
K-ras and p53 Mutations in Colonic Lavage Fluid of Patients with Colorectal Neoplasias
Authors: Heinzlmann M. , Neynaber S. , Heldwein W. , Folwaczny C.
Published: April 2003

Background: The adenoma-carcinoma sequence has its molecular basis in several gene mutations of which K-ras and p53 are of paramount importance. The aims of this study were to evaluate whether these genetic alterations can be detected in colonic lavage fluid from patients with colorectal adenomas and carcinomas. Methods: In 45 patients with adenomas, 20 patients with colorectal carcinomas and 38 patients with non-neoplastic and noninflammatory diseases of the colon p53 and K-ras mutations were evaluated in colonic lavage fluid employing single-strand confirmation polymorphism analysis and dot-blot hybridization, respectively. Results: Mutations of the K-ras and the p53 gene were found in 15.6% (p = 0.065) of patients with adenomas, in 25.0 % (p = 0.016) of patients with carcinomas and in 2.6% in the control group. Conclusion:  Genetic alterations in the colonic lavage fluid could be an additional diagnostic tool for the surveillance of patients with colorectal neoplasias.
Influence of Interleukin-10 on the Interleukin-1 Receptor Antagonist/Interleukin-1β Ratio in the Colonic Mucosa of Ulcerative Colitis
Authors: Ishizuka Kisei , Sugimura Kazuhito , Homma Terasu , Matsuzawa Jun , Mochizuki Tsutomu , Kobayashi Masaaki , Suzuki Kouji , Otsuka Kazuaki , Tashiro Kazunori , Yamaguchi Osamu , Asakura Hitoshi
Published: April 2003

A decrease in the ratio of IL-1ra/IL-1β produced regionally by the colonic mucosa of patients with ulcerative colitis (UC) is believed to play a role in the pathogenesis of UC. To investigate factors influencing intramucosal IL-1ra/IL-1β ratios, we evaluated polymorphism of the IL-1ra gene and the production of mucosal cytokines in Japanese patients with UC. Colonic biopsy specimens of mucosal tissue were placed in organ cultures for 24 h. Then, the supernatant concentrations of IL-1β, IL-1ra, IL-8, IL-4, IL-10, and TGF-β were assayed by ELISA. Genomic DNA was extracted from patient peripheral blood samples, then IL-1ra gene polymorphism was determined using PCR amplification. The mucosa from patients with active stage UC showed a tendency toward a decreased IL-1ra/IL-1β ratio. In the resolving stage, IL-1ra/IL-1β ratios increased with increasing IL-10 and TGF-β concentrations. The addition of human recombinant IL-10 to the culture supernatants produced concentration-dependent inhibition of IL-1β. In Japanese patients with UC, the IL-1ra allele gene 2 phenotype had no effect on the IL-1ra/IL-1β ratio. Our findings suggest that a relative deficiency of IL-10 in patients with UC may contribute to persistent inflammatory changes.
Mucins and Immune Reactions to Mucins in Ulcerative Colitis
Authors: Hayashi Toshiaki , Ishida Tadao , Motoya Satoshi , Itoh Fumio , Takahashi Tohru , Hinoda Yuji , Imai Kohzoh
Published: April 2003

Ulcerative colitis (UC) is an inflammatory bowel disease of undetermined etiology. Mucins, mainly produced by goblet cells, protect colon cells from various kinds of stress. Alteration in the quality or quantity of mucins may be the cause of the disease. Another possible cause is immune reactions to colonic cells. Anti-MUC1 antibodies were detected in the sera of patients with UC. Antibodies would destroy the colonic cells through antibody-dependent cell-mediated cytotoxicity. We reviewed the significance of mucins as well as humoral and cellular immunity in the pathogenesis of UC.
Interleukin-18 and Crohn’s Disease
Authors: Kanai Takanori , Watanabe Mamoru , Okazawa Akira , Sato Toshiro , Hibi Toshifumi
Published: April 2003

The etiology and pathogenesis of inflammatory bowel disease remains an area under intense investigation. Crohn’s disease (CD) is characterized by a marked accumulation of activated Th1 type CD4+ T cells and macrophages in inflamed intestinal mucosa. IL-18 is a recently described cytokine that mainly exists in activated macrophages and shares biological activities with IL-12 in driving the development of Th1 type CD4+ T cells by inducing interferon-γ. To clarify the role of IL-18 in intestinal inflammation in CD, we assessed the functional role of IL-18 in regulating intestinal mucosal lymphocytes in human CD and murine CD model.
Germinated Barley Foodstuff Feeding
Authors: Kanauchi Osamu , Iwanaga Toshihiko , Mitsuyama Keiichi
Published: April 2003

A germinated barley foodstuff (GBF) contained glutamine-rich protein and the hemicellulose-rich fiber was made from brewer’s spent grain by physical isolation (milling and sieving). Both in vivo and in vitro studies demonstrated that the fiber fraction of GBF supports maintenance of epithelial cell populations, facilitates epithelial repair, and suppresses epithelial nuclear factor ĸB-DNA binding activity through generating increased short-chain fatty acid (especially butyrate) production by luminal microflora which includes Bifidobacterium and Eubacterium, thereby preventing experimental colonic injury. The fiber fraction also modulates stool water content by its high water-holding capacity. The protein fraction which contains larger glutamine prevents experimental small bowel injury. Based on these observations, clinical studies were initiated in patients with mild to moderate active ulcerative colitis. The patients who had been unresponsive to or intolerant of standard treatment received 30 grams of GBF feeding daily in a nonrandomized, open-label fashion. At 4 weeks, this treatment resulted in a significant clinical and endoscopic improvement independent of disease extent. The improvement was associated with an increase in stool butyrate concentrations and in luminal Bifidobacterium and Eubacterium levels. After the end of GBF treatment the patients had an exacerbation of the disease. GBF was safe and well tolerated. These results indicate that GBF feeding is a potentially attractive treatment in patients with ulcerative colitis.
Transcription Factor-Targeted Therapies in Inflammatory Bowel Disease
Authors: Mitsuyama Keiichi , Suzuki Asuka , Tomiyasu Nobuo , Takaki Kosuke , Toyonaga Atsushi , Sata Michio
Published: April 2003

Although the causes of inflammatory bowel disease currently are not fully understood, increasing evidence implicates cytokines as key factors in the development of this disorder. The rationale for cytokine-targeted therapy for inflammatory bowel disease has been refined significantly, and clinical studies have been initiated. Recent investigations have focused on transcription factors that regulate production and activation of cytokines, including the nuclear factor-ĸB, the p38 mitogen-activated protein kinase, the peroxisome proliferator-activated receptor-γ, and the Janus kinases/signal transducers and activator of transcription pathways. Although their exact role in inflammatory bowel disease is still unknown, further studies may lead to identification of additional possible targets for therapeutic intervention that could improve management of the disease.
Estimation of Mucosal Inflammatory Mediators in Rat DSS-Induced Colitis
Authors: Hirata Ichiro , Murano Mitsuyuki , Nitta Masatoshi , Sasaki Shin-ichi , Toshina Ken , Maemura Kentaro , Katsu Ken-ichi
Published: April 2003

In order to investigate the mucosal injury mechanism in UC, we made dextran sulfate sodium (DSS)-induced colitis in rat and examined pathological findings, MPO activity, PGE2 level, and local mRNA expression and secretion of IL-1β, TNF-α, GRO/CINC-1 and IL-10 in DSS colitis mucosa. Moreover, we estimated the correlation between the severity of mucosal damage and changes of these local inflammatory mediators’ values. Neutrophil infiltration was marked and MPO activity was locally increased in proportion to the severity of mucosal damage. The mRNA expression and secretion of IL-1β, GRO/CINC-1 and IL-10 were increased. Especially, the secretions of IL-1β and GRO/CINC-1 were increased in proportion to the severity of mucosal damage. However, those of TNF-α were not increased in the colitis mucosa. An abnormal macrophage function and the presence of macrophage subtypes producing different cytokines would be predicted from our TNF-α data. The lesion was less severe in the colonic mucosa with higher levels of endogenous PGE2, while it was more severe in the colonic mucosa with lower levels of endogenous PGE2, implicating this compound as an inhibitory factor against the development of inflammation in the affected mucosa. Our results suggest that PGE2 might have therapeutic applicability to UC.
Effect of Cholecystokinin-B Gastrin Receptor Blockade on Chemically Induced Colon Carcinogenesis in Mice: Follow-Up at 52 Weeks
Authors: Fontana M.G. , Moneghini D. , Villanacci V. , Donato F. , Rindi G.
Published: April 2003

Background/Aims: The potential role of gastrin and the cholecystokinin-B (CCK-B)/gastrin receptor in the genesis of colon cancer is debated. Aberrant crypt foci (ACF) are considered to be preneoplastic lesions of colon cancer. We aimed to assess whether the CCK-B/gastrin receptor antagonist, CR2945, may prevent the development of ACF and adenocarcinoma in the experimental model of dimethylhydrazine (DMH)-induced colorectal cancer. Materials and Methods: 226 CD1 mice were randomized into 3 groups (sham, control and treated) and received intraperitoneal injections of NaCl 0.9%, DMH, and DMH + CR2945, respectively, for 5 weeks. 168 mice were sacrificed at 15, 38, 45 and 52 weeks after the first injection day. The colon and rectum were investigated for frequency, multiplicity and distribution of ACF as well as for adenocarcinoma at histology. The expression of gastrin was assessed in tumor samples at histology by immunohistochemistry. Results: ACF frequency and multiplicity significantly increased with time in both controls and treated mice with no difference between groups except that at week 45. 38.8% of controls and 14.3% of treated mice developed cancer (p = 0.004). No cancer was positive for gastrin at immunohistochemistry. The mean number of cancers per mouse and the proportion of mice with cancer increased with time with statistically significant difference between controls and treated mice at week 38 only but not afterwards. A significant correlation between cancer and ACF frequency (r = 0.35) and multiplicity (r = 0.25) was observed. Conclusions: Our findings support the preneoplastic significance of ACF and indicate that CR2945 treatment does not interfere with the DMH-induced cancerigenic process.
Prospective Comparison of Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography in the Preoperative Assessment of Masses in the Pancreatic Head
Authors: Glasbrenner B. , Schwarz M. , Pauls S. , Preclik G. , Beger H.G. , Adler G.
Published: April 2003

Aims: To compare the diagnostic value of endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in the differentiation of malignant from benign masses in the pancreatic head. Methods: Within 14 months 95 prospective patients with masses in the pancreatic head were assigned for preoperative EUS and ERCP. Both procedures were performed and recorded according to a standardized protocol. Based on intraoperative findings and histology, 50 patients (53%) suffered from malignant and 45 patients (47%) from benign (inflammatory) tumors. Results: Success rates were 96% for EUS and 95% for ERCP. The overall results for EUS and ERCP to predict malignant masses were, respectively: sensitivity 78 and 81%, specificity 93 and 88%, positive predictive value 93 and 89%, negative predictive value 78 and 80%, and diagnostic accuracy 85 and 84%. When EUS and ERCP were taken together, the sensitivity was 92% (specificity 85%), but the diagnostic accuracy (89%) was not significantly enhanced. The results for EUS to diagnose lymph node metastases preoperatively were: sensitivity 55%, specificity 91%, positive predictive value 69%, negative predictive value 84%, and accuracy 81%. Conclusions: EUS and ERCP have similar diagnostic accuracies to separate malignant from benign masses in the pancreatic head. Combination of both procedures is not superior to the use of one modality alone. Abnormal lymph nodes visualized on EUS in patients with inflammatory masses in the pancreatic head due to chronic pancreatitis should be interpreted cautiously.
Improved Healing of Extraperitoneal Intestinal Anastomoses in the Early Phase when Surrounded by Omentum
Authors: Pierie J.P.E.N. , de Graaf P.W. , van Dijk M. , Renooij W. , van Vroonhoven T.J.M.V. , Obertop H.
Published: April 2003

Background: The extra-anatomical position of a cervical oesophagogastrostomy is a reason for impaired anastomotic healing, but transposition of the omentum that is covered with mesothelial cells may be a way to improve that. Method: This hypothesis was tested in a rat model. An end-to-end jejuno-jejunostomy was placed subcutaneously in group I (n = 29), subcutaneously surrounded by omentum in group II (n = 29) and intra-abdominally surrounded by omentum in group III (n = 20). After 3, 7 or 14 days, the rats were sacrificed and bursting pressure (BP) of the anastomosis or jejunum was measured and the hydroxyproline (HP) level was determined. Results: In group I 5/29, in group II 2/29 and in group III 0/20 rats died following anastomotic leakage (nonsignificant) and were excluded from other measurements. BP was decreased after 3 days in group I (60 ± 9 mm Hg) compared with group II (101 ± 8 mm Hg) and group III (107 ± 11 mm Hg) (p = 0.002). After 7 days, BP in groups I (122 ± 10 mm Hg) and II (132 ± 10 mm Hg) were lower as compared with group III (230 ± 8 mm Hg) (p < 0.001). Differences in HP levels were not statistically significant between the groups after 3, 7 and 14 days. Conclusion: The healing of intestinal anastomoses in an extraperitoneal position is improved in the early phase only when surrounded by omentum.
Traumatic and Postoperative Ischemic Liver Necrosis: Causes, Risk Factors and Treatment
Authors: Røkke Ola , Nesvik Idunn , Søndenaa Karl
Published: April 2003

Background: To study the cause and outcome of ischemic liver necrosis and suggest treatment of these patients. Methods: Retrospective study of 13 patients with ischemic liver necrosis treated at our departments from 1990 until 1997. Results: Ischemic liver necrosis was caused by general hypoxia (n = 1) or acute arterial occlusion (n = 12) of the celiac and superior mesenteric artery (SMA, n = 3), proper hepatic artery (PHA, n = 1), right hepatic artery (RHA, n = 2), left hepatic artery (LHA, n = 2) and intrahepatic vessels (n = 4). Six of the cases were related to surgical procedures, 5 of these (38%) were unintended arterial injuries after biliary surgery. Ten patients (77%) had risk factors contributing to the development of liver necrosis: septicemia (n = 4), jaundice and septicemia (n = 2), shock and hypoxia (n = 3) and alcoholic cirrhosis (n = 1). Five patients (38%) needed resection of the liver necrosis due to infected necrosis. Three patients (23%) died; two of these had celiac/SMA occlusion. One died due to complete gastrointestinal ischemia and severe lactacidosis, two died of multiorgan failure after bile leakage and septicemia. Conclusion: Ischemic liver necrosis is mainly caused by arterial occlusion due to arteriosclerosis, arterial transection during biliary surgery or blunt liver trauma, and seldom occurs without additional risk factors. 50% of the patients develop infected necrosis and need liver resection. Patients with sterile necrosis may recover without surgical procedures of the liver. The mortality in patients with central (celiac/SMA) and peripheral (CHA, PHA, RHA, LHA, intrahepatic branches) occlusions was 67% (2/3) and 11% (1/9), respectively.
Serum Soluble Interleukin-2 Receptor as a Predictor of Lymph Node Metastasis in Early Gastric Cancer
Authors: Murakami Saburo , Sakata Hideto , Tsuji Yoshitaka , Okubo Kastuhiko , Hamada Setsuo , Hirayama Rennzo
Published: April 2003

Background: In the present study, we investigated the clinical significance of serum soluble IL-2R as a predictor of lymph node metastasis in patients with early gastric cancer. Patients and Methods: Seventy-four patients with early gastric cancer were enrolled in this study. Levels of serum soluble IL-2R were measured by an enzyme-linked immunosorbent assay. Result: Significant differences in serum soluble IL-2R between the control group and cases of T1 were not recognized. On the other hand, levels of serum soluble IL-2R in 74 patients with early gastric cancer (T1) were significantly lower than those of T2, T3, and T4 (p < 0.05). There were no significant differences in serum soluble IL-2R between cases of mucosal and submucosal invasion (379 ± 42 vs. 382 ± 35 U/ml). Six of 35 patients with submucosal invasion (17.1%) had lymph node metastasis, but none of the 39 patients with mucosal invasion. In the 6 cases showing lymph node metastasis, the macroscopic types were IIc + Ul(+) in 4, and IIc + IIa and IIc + IIb in 1, respectively. Histopathologically, there were 5 poorly and 1 moderately differentiated adenocarcinomas. In 6 cases with lymph node metastasis, serum soluble IL-2R levels were significantly higher than in those without lymph node metastasis (556.8 ± 73 vs. 329 ± 22 U/ml, respectively, mean ± SEM, p < 0.05). Five of these 6 cases demonstrated statistically significantly increased levels of serum soluble IL-2R (sensitivity 83%, specificity 63%), suggesting serum soluble IL-2R as a predictor of lymph node metastasis in early gastric cancer (p < 0.05). Conclusion: According to these data, in patients of early gastric cancer with increased levels of serum soluble IL-2R, endoscopic mucosal resection or minimal invasive gastrectomy without dissection of regional lymph nodes should be avoided, since there is a high risk of lymph node metastasis.
Acute Appendicitis during Pregnancy
Authors: Eryilmaz Ramazan , Şahin Mustafa , Baş Gürhan , Alimoglu Orhan , Kaya Bülent
Published: April 2003

Background: To analyze the diagnosis and surgical treatment of acute appendicitis during pregnancy. Methods: The records of 24 pregnant patients who underwent surgery with preliminary diagnosis of acute appendicitis between January 1990 and July 2000 were reviewed retrospectively. Results: Between January 1990 and July 2000, there were 31,480 deliveries and the incidence of acute appendicitis was 1/1,312. Twenty patients had pathologically proven acute appendicitis (83.3%). Of the remaining 4 patients, one had hemorrhagic ovarian cyst, one had ovarian cyst rupture and in two cases no surgical pathology was diagnosed. Gestational stage at the diagnosis was first trimester in 7 patients, second trimester in 12 patients and third trimester in 5 patients. Five patients had abortions and premature delivery occurred in 2 patients. Conclusion: Diagnosis of acute appendicitis is difficult in pregnancy. Delay in diagnosis and surgery results in increase in complications. Emergency surgical intervention should be performed when acute appendicitis is suspected during pregnancy.
Outcome of Temporary Stomas
Authors: Kairaluoma M. , Rissanen H. , Kultti V. , Mecklin J.-P. , Kellokumpu I.
Published: April 2003

Purpose: The purpose of this study was to examine the outcome of patients to whom a temporary stoma was constructed in our institution. Method: The outcome of patients operated on over an 8-year period was prospectively examined. Special attention was given to the influence of age on complications and closure of stomas. Results: Between 1989 and 1996, a total of 349 intestinal stomas were constructed in 342 patients. In 141 of these patients, the stoma could be considered as temporary. The 30-day mortality rate was 7%. The overall complication rate was 50%. Pure stoma-related complications were observed in 12% of the patients. The final closure rate of temporary stomas was 67%. The closure rate was significantly higher if the temporary stomas were of the double-barrel type. There was no significant difference in the closure rate between patients with benign and malignant diseases, but the rate decreased significantly in age groups over 70 years. Conclusions: Forty percent of stomas constructed are considered as temporary, but only two-thirds of temporary stomas are closed subsequently. Especially end stomas tend to become permanent in patients over 70 years of age, although the morbidity rates of stoma closure do not differ from those of younger patients.
Partial Fistulotomy and Modified Cutting Seton Procedure in the Treatment of High Extrasphincteric Perianal Fistulae
Authors: Durgun Vedat , Perek Asiye , Kapan Metin , Kapan Selin , Perek Sadı
Published: April 2003

Aim: In our prospective study the method of partial distal fistulotomy and modified cutting seton for high extrasphincteric perianal fistulae is discussed. Methods: 10 patients (9 males and 1 female) with high extrasphincteric perianal fistulae were treated with partial distal fistulotomy and modified cutting seton. Four or five threads were introduced through the tract; one was tied tightly at the end of the operation, others were tightened every 10th day. While the tied thread cut the tissue, the others drained the tract. The follow-up period ranged from 3 months to 9 years. Results: None of the patients developed major fecal incontinence. 2 of the 10 patients complained of incontinence due to flatus. Conclusion: Distal fistulotomy and modified cutting seton can be used in perianal fistulae with high anal or rectal opening, because it combines the effects of both cutting and loose setons and because the postoperative results regarding continence are satisfactory.
The French Experience – the Pharmacist, General Practitioner and Patient Perspective
Authors: Bouchez Jacques , Vignau Jean
Published: April 2003

High-dose buprenorphine (Subutex®) has been available in France as a maintenance treatment since February 1996. Results from a twice yearly survey of pharmacists, general practitioners (GPs) and patients themselves in the use of Subutex® appeared to be representative of the general substitution therapy situation in France. Results from May 1997 were encouraging, with improved relationships between pharmacists and patients, and GPs and patients being reported in all three surveys. The most commonly prescribed dosage of buprenorphine (6–8 mg) was within the recommended range, although there was evidence that this was usually taken as several daily intakes by the majority of addicts. Although intravenous injection may occur in some cases, illicit resale was suspected only in a few cases. Treatment efficacy was high and retention at six months was good since patients had a positive opinion of their treatment and reported few adverse effects. Further improvement in the relationships between GPs and pharmacists is desirable to increase the success of the treatment programme.
Compulsory Drug Treatment in Canada: Historical Origins and Recent Developments
Authors: Fischer Benedikt , Roberts Julian V. , Kirst Maritt
Published: April 2003

In Canada, illicit drug use and addiction have traditionally been considered as a criminal justice problem and have been addressed from a legal perspective. Over the past century, a medical approach to drug addiction has slowly crept into the criminal justice processing of drug offenders. This has happened through the combination of principles of punishment with principles of addiction treatment in the sentencing of drug offenders to create a distinct application of ‘compulsory drug treatment’ in Canada. However, this evolution has occurred sporadically over time, with punishment and coercion as predominantly the main approach to dealing with this population. This evolution has recently culminated in Canada with the development of two criminal justice approaches to dealing with the substance use problems of drug offenders that incorporate concepts of punishment and treatment more equally than ever before – conditional sentencing and drug courts. This paper outlines the historical evolution of concepts of ‘compulsory treatment’, discusses such examples of contemporary ‘compulsory treatment’ as conditional sentencing and drug courts, and analyses the implications, concerns and challenges associated with these tools currently used in the sentencing of drug offenders in the Canadian context.
Three-Year Follow-Up Study of Heroin Users in Bratislava
Authors: Okruhlica L. , Mihalkova A. , Klempova D. , Skovayova L.
Published: April 2003

The principal goal of the present study was to find out the prospects of patients who enter a treatment facility due to their opioid dependence in the specific socioeconomic conditions of a transforming Central European country. The prospective follow-up study of a cohort of 351 patients, 76% males and 24% females, with an average age of 21.5 years (SD 4.8 years) was evaluated 1 and 3 years after the patients were taken into treatment. The treatment intake was performed in a specialized comprehensive treatment facility in Bratislava, Slovak Republic. One and 3 years later, 79 and 70% of the patients, respectively, were contacted. The results show that after 3 years, 30% of patients (106) had been fully abstinent from all opioids for at least 6 months, 6% (19) had been abstinent less than 6 months, 10% (35) were on substitution treatment and 25% (86) were regular heroin users at that time. A significantly better outcome after 3 years was observed among those subjects who were at work or at school at the time of admission. Despite different socioeconomic conditions, the results demonstrate that findings concerning the outcome of opiate users undergoing treatment are consistent with those from other parts of the world.
Stroke and Functional Rehabilitation: The Chinese Experience
Authors: Li Shun-wei
Published: April 2003

According to an epidemiological study of cerebrovascular disease carried out in China in 1986, the prevalence, incidence, and mortality rates were 159.93/100,000, 115.61/100,000, and 31.33/100,000, respectively. These figures were high compared to available epidemiological data for the rest of the world. This highlights the fact that, as in other countries, functional rehabilitation after stroke is an important medical and social need in China. Clinical experience shows that within a few hours to a few months after a stroke, a large proportion of patients spontaneously experience partial, or on occasion, complete recovery from neurologic symptoms. However, functional rehabilitation in medical care units is required because it assists in and accelerates the recovery of impaired function. Almitrine-raubasine has been used to improve functional rehabilitation after stroke for some time in China. By enriching the oxygen content of arterial blood, it brings more oxygen to the cerebral tissues and therefore promotes cerebral aerobic metabolism during ischemia. In the acute phase of stroke, positron emission tomography showed, in man, that almitrine-raubasine helps normalize the ischemic penumbra area, as shown by an improvement in the coupling between oxygenation and perfusion. Long after stroke, single photon emission computed tomography showed that almitrine-raubasine restores normal cerebral vasodilator response to acetazolamide. With a view to further documenting the clinical efficacy of almitrine-raubasine on the convalescent period of patients with cerebrovascular disease, a double-blind, placebo-controlled study is planned. One hundred patients with ischemic cerebrovascular disease in the territory of the carotid artery will be included 4–6 weeks after the acute onset. Two tablets daily of almitrine-raubasine or placebo will be prescribed for 3–6 months. Before treatment, there will be a 2-week washout period for all other drugs, except for antihypertensive and antidiabetic drugs. In addition to complete clinical monthly examinations, neurological functional deficit scores, Barthel index, Hasagawa Dementia scales, and CT scan are scheduled. The study results should confirm those reported in the scientific literature: although untreated patients may show spontaneous improvement, almitrine-raubasine should accelerate patients’ functional rehabilitation.
NIS-LL: The Primary Measurement Scale for Clinical Trial Endpoints in Diabetic Peripheral Neuropathy
Authors: Bril Vera
Published: April 2003

Regulatory authorities favour the use of clinical endpoints, over surrogate endpoints, to demonstrate the efficacy of therapeutic agents for diabetic peripheral neuropathy (DPN). Progress in the quantification of the severity of DPN has been observed in recent years. The NIS-LL (Neuropathy Impairment Score in the Lower Limbs) is a new scale which quantifies the neurological function in DPN. This scale for determining the neuropathy impairment in DPN optimises the chances of demonstrating clinical change following pharmaceutical intervention in patients with early-stage neuropathy. The use of the NIS-LL in clinical trials, together with other tests measuring nerve function, pain and risk of foot ulcer, provides the best opportunity to evaluate the efficacy of new therapeutic agents for the treatment of DPN.
Advances in Neuroprotection Trials
Authors: Lees Kennedy R.
Published: April 2003

With technological assistance, approaches to acute stroke trials may be improved. Dose selection, eligibility criteria, control of confounding factors and endpoints can each be optimised. Adaptive randomisation techniques and Bayesian approaches can assist not only dose selection, but also balance of prognostic factors between treatment groups. Magnetic resonance imaging can facilitate enrichment of the trial population with potential responders. Utilisation of existing trial databases can enhance statistical approaches to outcome assessment. Confounding imbalance may also be limited by controlling or adjusting for concomitant conditions and their management. Recent trials have not yet identified a neuroprotectant, but have greatly assisted the prospects of success.