| 1. |
- Ahrenstedt, O, et al.
(författare)
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Increased luminal release of hyaluronan in uninvolved jejunum in active Crohn's disease but not in inactive disease or in relatives.
- 1992
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Ingår i: Digestion. - 0012-2823 .- 1421-9867. ; 52:1, s. 6-12
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Tidskriftsartikel (refereegranskat)abstract
- Recently obtained data suggest that there is a subclinic inflammatory activity in the apparently uninvolved intestinal mucosa in Crohn's disease (CD). As CD is characterized by an activation of connective tissue and fibrosis, we investigated the extent to which hyaluronan (HA), an essential component of the connective tissue, was released into the lumen of an isolated jejunal segment in CD patients and in relatives. Patients with active CD of the terminal ileum (CD activity index, CDAI, > 150; n = 14), patients with CD in remission (CDAI < 150 n = 10), first-degree relatives of the CD patients (n = 21) and healthy controls (n = 43) were orally intubated with a catheter allowing occlusion and perfusion of a segment of the proximal jejunum. The jejunal fluid concentration of HA was 65 +/- 45 micrograms/l in patients with active CD in the terminal ileum, significantly higher than the value for 43 healthy controls (42 +/- 23 micrograms/l; p < 0.05), and the corresponding values for patients in remission (42 +/- 23 micrograms/l) and for first-degree relatives of the CD patients (53 +/- 52 micrograms/l), were not increased compared to the control group. To localize HA in the tissue, small bowel biopsies were taken during surgery from patients with CD and from controls and affinity stained for HA. There was an intense staining for HA in the lamina propria of the villi, both in biopsies from patients with CD and from controls, but no staining in the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 2. |
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| 3. |
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| 4. |
- Brannstrom, J, et al.
(författare)
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Helicobacter pylori stimulates DNA synthesis in a small intestinal cell line in vitro
- 1998
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 59:1, s. 33-39
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Tidskriftsartikel (refereegranskat)abstract
- <b>Background:</b> <i>Helicobacter pylori</i>, which causes gastritis and peptic ulcer, seems to be an important factor in the pathogenesis of gastric cancer and MALT lymphoma. Thus our aim was to examine whether <i>H. pylori</i> influences DNA synthesis in epithelial cells in vitro. <b>Methods:</b> Sonicated and water extracts of <i>H. pylori</i> (cytotoxic strains NCTC 11637, 88-23 and A5, and a noncytotoxic isogenic mutant of A5, A5 vac A) were diluted to a final concentration of 1/1,000, 1/100, 1/50 and 1/10. Water extracts of <i>Escherichia coli</i> were used as reference. IEC-6 cells were incubated during 24 h with fragments of <i>H. pylori</i> or extracts of the concentrations described above. The cells were labeled with <sup>3</sup>H-methylthymidine for 4 h and processed for autoradiography. DNA synthesis was evaluated by the labeling index (LI). <b>Results:</b> The LI% of controls was 15.6 ± 5.1%. All the water extracts and sonicated strains of <i>H. pylori</i> increased the LI% in a dose-dependent manner (p < 0.001). The highest concentrations of the sonicated strains tended to reduce the LI%, although these values were still higher than those of the control group. The water extracts of <i>E. coli</i> increased the LI% in a dose-dependent manner (p < 0.0001). <b>Conclusion:</b> <i>H. pylori</i> stimulates DNA synthesis in epithelial cells in vitro, but no association was found with the presence of cytotoxin production. Our results suggest that hitherto unknown components of <i>H. pylori</i> may contribute to the increase in cell proliferation observed in gastritis and to the development of MALT lymphoma and gastric cancer.
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| 5. |
- de Boer, NKH, et al.
(författare)
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6-thioguanine treatment in inflammatory bowel disease : A critical appraisal by a European 6-TG working party
- 2006
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 73:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel.
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| 6. |
- Farzad, A, et al.
(författare)
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Luminal release of hyaluronan (hyaluronic acid) in intestinal ischemia in the rat.
- 1993
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Ingår i: Digestion. - 0012-2823 .- 1421-9867. ; 54:3, s. 168-72
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Tidskriftsartikel (refereegranskat)abstract
- Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be pivotal for an optimal hydration of tissues. The lamina propria of the intestinal villi is characterized by a high concentration of HA. Increased amounts of HA are observed in the intestinal lumen in patients with Crohn's disease. We have evaluated whether epithelial denudation as such is sufficient to increase the concentration of HA in the lumen of the small intestine. Epithelial damage was accomplished by reversible ischemia-reperfusion injury to the rat ileum and the concentration of HA was determined in luminal perfusate. The perfusate concentration of HA was increased from 26 +/- 8 micrograms/l before ischemia, to 68 +/- 13 and 41 +/- 12 micrograms/l 0-30 and 30-60 min after a 60-min period of subtotal ischemia without venous stasis (p < 0.05). In sham-operated animals, in contrast, the perfusate concentration of HA was virtually unchanged (31 +/- 18, 13 +/- 3 and 10 +/- 1 microgram/l, respectively). Specific staining for HA on sections revealed loss of HA from the villus tips after ischemia. The results show that epithelial denudation results in loss of HA from the villus interstitium to the intestinal lumen.
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| 7. |
- Freedman, J, et al.
(författare)
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Presence of bile in the oesophagus is associated with less effective oesophageal motility
- 2002
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 66:1, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Reflux of bile to the oesophagus has been shown to be of importance in the development of gastro-oesophageal reflux disease. This study aims to assess oesophageal motility patterns in relation to acid and bile reflux to the oesophagus. <i>Methods:</i> Forty-nine subjects with and without reflux disease underwent 24-hour ambulatory recordings of oesophageal pH, bile and 3-channel manometry. Gastroscopy was performed to assess severity of oesophagitis. The percentage of effective peristaltic contractions (oesophageal contractions with a peristaltic pattern and a pressure >30 mm Hg) were correlated to the degree of acid and bile reflux. Ten subjects were re-evaluated within 2 years post-fundoplication. <i>Results:</i> Acid and bile reflux were associated with fewer effective contractions (R<sup>2</sup> = 0.07, p = 0.06 and R<sup>2</sup> = 0.21, p = 0.008, respectively). However, in a multivariate model including acid, bile, age and gender dependency, only bile could show a systematic effect on the variation in percentage of effective peristaltic contractions (R<sup>2</sup> = 0.22, p = 0.001). One year after laparoscopic fundoplication, 24-hour oesophageal motility was unchanged. <i>Conclusion:</i> Reflux of duodenal juice to the oesophagus is associated with less effective oesophageal motility, which in turn can perpetuate the disease by less effective oesophageal clearance of bile and acid. The reduced oesophageal motility is not reversed by fundoplication.
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| 8. |
- Granberg, Dan, et al.
(författare)
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Regression of a large malignant gastrinoma on treatment with Sandostatin LAR : a case report
- 2008
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 77:2, s. 92-5
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Tidskriftsartikel (refereegranskat)abstract
- Gastrinomas may occur in the pancreas, duodenum or peri-pancreatic lymph nodes. The gastrin overproduction leads to the Zollinger-Ellison syndrome with multiple gastric and duoudenal ulcers and diarrhea. About two thirds of gastrinomas are malignant. Diagnosis is made by clinical history, gastroscopy, and measurement of serum gastrin, gastric juice pH, CT scan, endoscopic ultrasonography and somatostatin receptor scintigraphy. Surgery should always be considered if the liver is not involved. Proton pump inhibitors offer symptomatic relief. Medical therapy for tumor control includes biotherapy with alpha-interferon and somatostatin analogs yielding a response rate of about 10-15%, chemotherapy or targeted radiotherapy. We describe a patient with almost complete response on treatment with Sandostatin LAR (R), a long-acting somatostatin analog. In patients with metastatic gastrinomas not suitable for chemotherapy, interferon or targeted radiotherapy, single therapy with somatostatin analogs may be an alternative.
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| 9. |
- Hart, Andrew R, et al.
(författare)
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Diet in the aetiology of ulcerative colitis: A European prospective cohort study
- 2008
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Ingår i: Digestion. - : S. Karger AG. - 1421-9867 .- 0012-2823. ; 77:1, s. 57-64
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study. Methods: The study population was 260,686 men and women aged 20-80 years, participating in a large European prospective cohort study (EPIC). Participants were residents in the UK, Sweden, Denmark, Germany or Italy. Information on diet was supplied and the subjects were followed up for the development of ulcerative colitis. Each incident case was matched with four controls and dietary variables were divided into quartiles. Results: A total of 139 subjects with incident ulcerative colitis were identified. No dietary associations were detected, apart from a marginally significant positive association with an increasing percentage intake of energy from total polyunsaturated fatty acids (trend across quartiles OR = 1.19 (95% CI = 0.99-1.43) p = 0.07). Conclusions: No associations between ulcerative colitis and diet were detected, apart from a possible increased risk with a higher total polyunsaturated fatty acid intake. A biological mechanism exists in that polyunsaturated fatty acids are metabolised to pro-inflammatory mediators.
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| 10. |
- Jahnson, S, et al.
(författare)
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Anastomotic blood-flow reduction in rat small intestine with chronic radiation damage.
- 1998
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Ingår i: Digestion. - 0012-2823 .- 1421-9867. ; 59:2, s. 134-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Anastomoses in previously irradiated intestine are prone to leakage, possibly due to an impeded blood supply. Whether or not chronic radiation damage actually predisposes to a disturbed blood flow in the vicinity of anastomoses was investigated in the rat small bowel.METHOD: A 2-cm segment of rat ileum was irradiated with a single dose (21 Gy). After 20 weeks an anastomosis was created in the irradiated segment and in the corresponding segment of controls. Another 4 days later local blood flow was studied with the 14C-iodoantipyrine autoradiography technique in 16 sectors around the circumference both in the anastomotic segment and in a segment 4 mm apart.RESULTS: In the anastomotic segment, the average blood flow was reduced in irradiated compared with non-irradiated animals in the mucosal layer (p = 0.034), but not in the muscular layer (p = 0.08). In the mesenteric quadrant blood flow was reduced in irradiated compared with non-irradiated animals, both in the mucosal layer (p = 0.012) and in the muscular layer (p = 0.05). More irradiated than non-irradiated animals showed a blood-flow reduction to 15% or more in 13-16 sectors both in the mucosal (p = 0.015) and the muscular layer (p = 0.04).CONCLUSIONS: The results favor the hypothesis that anastomoses in previously irradiated intestine are vascularly compromized and thereby have an increased risk of leakage.
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| 11. |
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| 12. |
- Le, Nha, et al.
(författare)
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Real-world clinical practice of intensified chemotherapies for metastatic pancreatic cancer : results from a Pan-European questionnaire study
- 2016
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 94:4, s. 222-229
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe.Methods: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club. The questionnaire consisted of 20 questions, 14 regarding the use of intensified chemotherapy, 4 regarding demographics of the participants, and 1 to verify the active involvement in the management of metastatic pancreatic cancer.Results: Two hundred and thirteen responses were received and 153 entries were valid for analysis. Of those, 63.4% came from an academic institution, 51% were oncologists, and 52% treated more than 25 cases per year. A majority of responses (71%) were from Italy (40%), Germany (23%), and Spain (8%). As first-line therapy, 11% used gemcitabine +/- erlotinib, 42% used FOLFIRINOX, and 47% used gemcitabine + nab-paclitaxel. Of the intensified regimens, both were applied to equal parts, but the likelihood of protocol deviation was higher when using FOLFIRINOX (p < 0.01). FOLFIRINOX was considered more toxic than gemcitabine + nab-paclitaxel (neutropenia 88 vs. 68%; polyneuropathy 42 vs. 41%; rapid deterioration 42 vs. 31%). FOLFIRINOX was rated to achieve longer survival with an acceptable quality of life (52 vs. 44%). Moreover, 57% of participants thought that gemcitabine + nab-paclitaxel should be the backbone for further clinical trials in pancreatic cancer.Conclusion: Intensified chemotherapy is widely used in pancreatic cancer patients in Europe following its recent clinical approval. Interestingly, nab-paclitaxel and FOLFIRINOX were used at comparable frequency although the latter had to be de-escalated more often.
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| 13. |
- Lilja, Ingela, et al.
(författare)
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Tumor necrosis factor-alpha in ileal mast cells in patients with Crohn's disease
- 2000
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 61:1, s. 68-76
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reports that both intestinal and extraintestinal Crohn's disease (CD) had healed successfully after treatment with anti-tumor necrosis factor-alpha (TNF-a) antibody have strengthened the hypothesis that it has a role in the treatment of CD. The macrophage is one source of TNF-a. Intestinal mast cells are also thought to have a role in CD, but it is not known if human ileal mast cells express TNF-a. Aim: To find out whether TNF-a is expressed by mast cells in the ileal wall in CD patients and controls. Methods: TNF-a was sought immunohistochemically in full thickness specimens of ileal wall from patients with CD (histologically normal, n = 9, inflamed, n = 6) and controls (patients with colonic cancer, n = 8). Mast cells were identified by metachromasia and anti-mast cell tryptase immunoreactivity. Results: In all layers of the ileal wall, and in every specimen investigated, mast cells were the main cell type that expressed TNF-a immunoreactivity out of the TNF-a-labelled cells. The number of TNF-a-labelled mast cells was greater in the muscularis propria in patients compared with controls, both in uninflamed (1.7-fold, p < 0.05) and in inflamed bowel (4.6-fold, p < 0.002), greater in the submucosa in inflamed compared with uninflamed CD (1.6-fold, p < 0.01), and less in the lamina propria in inflamed compared with uninflamed CD (0.4-fold, p < 0.05). Conclusion: Mast cells are an important source of TNF-a in all layers of the ileal wall, and the increased density of TNF-a-positive mast cells in the submucosa and muscularis propria may contribute to the tissue changes and symptoms in CD.
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| 14. |
- Lundell, L
(författare)
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Commentary regarding nighttime reflux
- 2005
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 72:4, s. 228-228
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 15. |
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| 16. |
- Neopikhanov, V, et al.
(författare)
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40- to 100-kD protein(s) of Helicobacter pylori stimulate DNA synthesis in epithelial cell lines without affecting apoptosis
- 2000
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 61:1, s. 22-29
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Previous in vitro studies have demonstrated that water extracts and sonicates of <i>Helicobacter pylori </i>increase DNA synthesis in a small intestinal epithelial cell line. The aim of this study was to identify mitogenic factor(s) in a water extract of a <i>H. pylori</i> strain and to examine their effects on DNA synthesis and apoptosis in vitro. <i>Methods: </i>IEC-6 and FHs 74 cells were incubated for 24 h with different dilutions of a water extract of <i>H. pylori</i> (cytotoxic strain 88–23) or with 6 protein fractions obtained by gel filtration. Cells were labeled with tritiated thymidine and processed for autoradiography. DNA synthesis was evaluated by the labeling index (LI%). The proportion of IEC-6 cells undergoing apoptosis and/or necrosis was evaluated by flow cytometry using fluorescein isothiocyanate (FITC)-labeled annexin-V and propidium iodide. In vitro caspase activity was also determined as an alternative method for detection of apoptosis. <i>Results:</i> The water extract of <i>H. pylori</i> 88-23 markedly increased DNA synthesis in both epithelial cell lines (p < 0.01). A marked stimulation of DNA synthesis was also observed in IEC-6 cells incubated with fraction II- containing proteins of a molecular weight ranging between 40 and 100 kD (p < 0.01). A lesser stimulation of DNA synthesis was observed in cells incubated with higher concentrations of the other protein fractions (p < 0.01). Neither the water extract of <i>H. pylori</i> 88-23 nor the protein fraction II (40–100 kD) induced apoptosis in IEC-6 cells. <i>Conclusion:</i> A water extract of <i>H. pylori</i> 88-23 and a protein fraction containing proteins with molecular weights of 40–100 kD stimulate DNA synthesis in a rat and human small intestinal cell line. Apoptosis was unaffected by the water extract and by protein fraction II, which indicate that the <i>H. pylori</i>-derived mitogen(s) have the capacity to directly enhance epithelial cell proliferation in vitro.
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| 17. |
- Raab, Y, et al.
(författare)
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Enhanced intestinal synthesis of interleukin-6 is related to the disease severity and activity in ulcerative colitis.
- 1994
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Ingår i: Digestion. - 0012-2823 .- 1421-9867. ; 55:1, s. 44-9
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Tidskriftsartikel (refereegranskat)abstract
- The concentration of interleukin-6 (IL-6) was measured in the perfusion fluid from investigated rectal and sigmoid segments in patients with ulcerative colitis (UC). The colorectal release of this substance from segments with active inflammation was greatly increased compared with that found in healthy controls and correlated to the mucosal damage defined by plasma protein leakage and endoscopic findings. The perfusate/serum ratio of IL-6 was significantly higher than the corresponding ratio of albumin, indicating that the increased amount of IL-6 detected in the perfusion fluid was synthesized in the inflamed colorectal mucosa. A strong correlation between the concentrations of IL-6 and of tumor necrosis factor-alpha in perfusion fluid suggests that macrophages/monocytes are cells of importance in the stimulated local synthesis of IL-6. The calculated total colorectal release of IL-6 was significantly correlated to the serum concentrations of C-reactive protein and alpha 1-antitrypsin, demonstrating that the acute phase response in patients with UC reflects the amount of locally produced IL-6.
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| 18. |
- Schneider, A, et al.
(författare)
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Prevalence and Incidence of Autoimmune Pancreatitis in the Population Living in the Southwest of Germany
- 2017
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Ingår i: Digestion. - : S. Karger AG. - 1421-9867 .- 0012-2823. ; 96:4, s. 187-198
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> The prevalence and incidence of autoimmune pancreatitis (AiP) in those living in western countries are largely unknown. We aimed to determine the prevalence of AiP among patients with pancreatitis presenting to our tertiary referral center in Mannheim, Germany; and to estimate the incidence of AiP in the Southwest of Germany. <b><i>Methods:</i></b> We performed a retrospective cross-sectional analysis and determined the prevalence of AiP in patients with acute pancreatitis (AP) or chronic pancreatitis (CP). Patients (<i>n</i> = 704; alcoholic pancreatitis <i>n</i> = 373, nonalcoholic pancreatitis <i>n</i> = 331) were stratified into the Retrospective-Pancreas-Cohort (RPC, period 1998-2008, <i>n</i> = 534) and the Pancreas-Clinic-Cohort (PCC, periods 2008-2010 and 2013-2014, <i>n</i> = 170, with detailed investigation for features of AiP). Diagnosis of AiP was established by International-Consensus-Diagnostic-Criteria and Unifying-Autoimmune-Pancreatitis-Criteria. <b><i>Results:</i></b> In the RPC, the prevalence of AiP was 5.9% (<i>n</i> = 13/221) among individuals with nonalcoholic pancreatitis (<i>n</i> = 1/61 with AP, 1.6%; <i>n</i> = 12/160 with CP, 7.5%). In the PCC, the prevalence of AiP was 9.1% (<i>n</i> = 10/110) among patients with nonalcoholic pancreatitis (<i>n</i> = 2/24 with AP, 8.3%; <i>n</i> = 8/86 with CP, 9.3%), and 1.7% (<i>n</i> = 1/60) among subjects with alcoholic pancreatitis. We estimated the incidence of AiP with 0.29 per 100,000 population each year. <b><i>Conclusion:</i></b> The prevalence rate of AiP may account for 9% of patients with nonalcoholic pancreatitis but is almost never observed in patients with alcoholic pancreatitis. The incidence of AiP in Germany appears lower than 1 per 100,000 population.
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| 19. |
- Schneider, A, et al.
(författare)
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Risk of Cancer in Patients with Autoimmune Pancreatitis: A Single-Center Experience from Germany
- 2017
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Ingår i: Digestion. - : S. Karger AG. - 1421-9867 .- 0012-2823. ; 95:2, s. 172-180
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> Autoimmune pancreatitis (AIP) has been associated with an increased risk of malignant diseases. We aimed to describe the incidence of malignant diseases in patients with AIP compared to the general population and to characterize the clinical presentation of these patients. <b><i>Methods:</i></b> We retrospectively analyzed data from 28 patients with AIP presenting to the clinic (periods 1998 until 2010, 2012 until September 2015). We retrieved the expected cancer incidence of the general population from the German cancer registry. We determined the ratio of patients with malignant disease, characterized the clinical presentation of these patients, and calculated standardized incidence ratios (SIR). <b><i>Results:</i></b> We observed 6 malignant diseases in 5 patients with AIP (non-Hodgkin lymphoma, colon cancer, breast cancer and ovarian carcinoma, breast cancer, bladder cancer, <i>n</i> = 5/28, 17.9%) during an overall observation period of 223 person-years (2,675 months). The overall SIR of cancer in patients with AIP was 17.3 (95% CI 5.9-35.8), and the overall incidence rate of malignant diseases in these patients was significantly increased compared to the expected incidence in the German population (Fisher's exact test, <i>p</i> < 0.001). <b><i>Conclusion:</i></b> The incidence of malignant diseases in patients with AIP is significantly increased compared to the general population. Careful clinical monitoring is required in individuals with AIP to exclude the occurrence of malignancy.
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| 20. |
- Schober, Marvin, et al.
(författare)
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New Advances in the Treatment of Metastatic Pancreatic Cancer
- 2015
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Ingår i: Digestion. - : S. Karger. - 0012-2823 .- 1421-9867. ; 92:3, s. 175-184
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Forskningsöversikt (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an extremely poor overall survival (OS) compared to other solid tumours. As the incidence of the disease is rising and the treatment options are limited, PDAC is projected to be the 2nd leading cause of cancer-related deaths in the United States by 2030. A majority of patients are not eligible for curative resection at the time of diagnosis, and those that are resected will often relapse within the first few years after surgery. Summary: Until recently, the nucleoside analogue gemcitabine has been the standard of care for patients with non-resectable PDAC with only marginal effects on OS. In 2011, the gemcitabine-free FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan and oxaliplatin) showed a significant survival advantage for patients with metastatic PDAC in a phase III trial. In 2013, the Metastatic Pancreatic Adenocarcinoma Trial phase III trial with nano-formulated albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine also resulted in a significant survival extension compared to gemcitabine monotherapy. However, both intensified therapy regimens show a broad spectrum of side effects and patients need to be carefully selected for the most appropriate protocol. Key Message: In this study, recent advances in the chemotherapeutic options available to treat metastatic PDAC and their implications for today's treatment choices are reviewed.
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| 21. |
- Sekiguchi, M, et al.
(författare)
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Epidemiological Trends and Future Perspectives of Gastric Cancer in Eastern Asia
- 2022
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Ingår i: Digestion. - : S. Karger AG. - 1421-9867 .- 0012-2823. ; 103:1, s. 22-28
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> The global epidemiological situation of gastric cancer has changed considerably over time, and it is essential to understand the epidemiological trends and future perspectives of gastric cancer. <b><i>Summary:</i></b> Although gastric cancer was common in the United States less than a century previously, it is no longer common in this country. Currently, over 60% of gastric cancers are found in Eastern Asia. In some Eastern Asian countries such as Japan and Korea, population-based gastric cancer screening has been conducted using upper gastrointestinal endoscopy or radiography to lower gastric cancer mortality. Due to earlier detection of gastric cancer, the survival of patients with gastric cancer is more favorable in these countries than in other Western countries. Even in Eastern Asia, a remarkable decrease in the age-standardized incidence and mortality of gastric cancer has been observed. This downward trend is mainly due to the reduced <i>Helicobacter pylori</i> infection, and this trend is considered to continue. Nevertheless, both the absolute number of incident cases and deaths of gastric cancer are still increasing at present due to the aging population. For the time being, the management of gastric cancer in elderly population is a critical issue in Eastern Asia. The absolute numbers of gastric cancer cases and deaths are believed to peak in the near future, following the decreasing age-standardized incidence and mortality. <b><i>Key Messages:</i></b> After a long period, gastric cancer may become a rare cancer even in Eastern Asia, and new efficient approaches for its prevention, screening, and treatment are warranted.
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| 22. |
- Simrén, Magnus, 1966, et al.
(författare)
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Quality of life and illness costs in irritable bowel syndrome.
- 2004
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 69:4, s. 254-61
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Tidskriftsartikel (refereegranskat)abstract
- Quality of life is reduced in patients with irritable bowel syndrome, and the costs for this disease are substantial to society. During a meeting in London, UK, the IBiS club reviewed the literature on these subjects. Drawbacks and advantages with existing instruments to assess quality of life and costs were discussed and the clinical and scientific relevance of the current knowledge was assessed. A summary from the meeting is presented in this paper.
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| 23. |
- Sjöstedt, Camilla, 1970-, et al.
(författare)
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Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation
- 2005
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 72:4, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Background: Different theories have been presented to explain how atrophic gastritis may lead to gastric cancer development. One contributing factor could be impaired function of the gastric mucosal barrier. The aim of this study was to investigate if there are changes in gastric mucosal permeability to sucrose in atrophic gastritis. Methods: The study comprised 22 patients with atrophic gastritis and 21 normal controls. Gastritis was classified according to the Sydney system from endoscopic biopsies of the gastric corpus and antrum. All subjects were exposed to oral sucrose load (100 g), and the fraction of sucrose excreted in urine was measured by gas chromatography-mass spectrometry. Results: The fraction of sucrose excreted in urine after oral load was significantly increased in atrophic gastritis compared with controls (median 0.08 vs. 0.04%, p = 0.003). Sucrose excretion was positively related to the degree of chronic inflammation (median fraction excreted: mild inflammation 0.06%, moderate inflammation 0.08%, severe inflammation 0.18%, p = 0.04) rather than to the degree of atrophy in the gastric mucosa. Occurrence of intestinal metaplasia was also associated with significantly higher sucrose excretion. However, in multivariate analysis, including intestinal metaplasia, only the degree of inflammation was positively related to sucrose excretion. Conclusion: Atrophic gastritis is associated with increased sucrose permeability, suggesting paracellular leakage of the gastric mucosa. This leakage seems to be related to the degree of inflammation rather than the degree of atrophy. The findings may have implications for the diseases and complications associated with atrophic gastritis. Copyright © 2005 S. Karger AG.
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| 24. |
- Valeur, J, et al.
(författare)
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Fecal Fermentation in Irritable Bowel Syndrome: Influence of Dietary Restriction of Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols
- 2016
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Ingår i: Digestion. - : S. Karger AG. - 1421-9867 .- 0012-2823. ; 94:1, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may relieve symptoms in patients with irritable bowel syndrome (IBS). We investigated whether this diet alters microbial fermentation, a process that may be involved in IBS symptom generation. <b><i>Methods:</i></b> Patients with IBS were included consecutively to participate in a 4-week FODMAP restricted diet. IBS symptoms were evaluated by using the IBS severity scoring system (IBS-SSS). Short-chain fatty acids (SCFAs) were analyzed in fecal samples before and after the dietary intervention, both at baseline and after in vitro fermentation for 24 h. <b><i>Results:</i></b> Sixty-three patients completed the study. Following the dietary intervention, IBS-SSS scores improved significantly (p < 0.0001). Total SCFA levels were reduced in fecal samples analyzed both at baseline (p = 0.005) and after in vitro fermentation for 24 h (p = 0.013). Following diet, baseline levels of acetic (p = 0.003) and n-butyric acids (p = 0.009) decreased, whereas 24 h levels of i-butyric (p = 0.003) and i-valeric acids (p = 0.003) increased. Fecal SCFA levels and IBS symptom scores were not correlated. <b><i>Conclusion:</i></b> Dietary FODMAP restriction markedly modulated fecal fermentation in patients with IBS. Saccharolytic fermentation decreased, while proteolytic fermentation increased, apparently independent of symptoms.
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| 25. |
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| 26. |
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| 27. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Clinical management of gastric carcinoid tumors.
- 1994
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Ingår i: Digestion. - 0012-2823. ; 55 Suppl 3, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.
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| 28. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Interventional treatment of gastrointestinal neuroendocrine tumours.
- 2000
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Ingår i: Digestion. - 0012-2823. ; 62 Suppl 1, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine (NE) tumours of the gastrointestinal tract (carcinoids and endocrine pancreatic tumours) are rare diseases. In the presence of liver metastases these patients may suffer from disabling symptoms due to hormone overproduction. Patients with localized disease can be resected for cure and also patients with liver metastases can undergo potentially curative tumour resection. However, long-term follow-up of the latter cases indicates frequent recurrence of tumour. Using close biochemical monitoring of tumour markers combined with newer techniques for tumour visualization, these recurrences can often be diagnosed at an early stage so that repeat surgical procedures can be performed. During the last years very active surgery has been recommended for NE tumours, many of which have a relatively slow growth. Even in patients not amenable to curative liver surgery, debulking can be considered if the main tumour burden can be safely excised. The primary aim of this type of treatment is palliation of hormonal symptoms. An important question is whether the aggressive treatment actually prolongs survival. No prospective studies have been performed. Such studies are hampered by the lack of strict surgical programs running over long periods and the relative rarity of NE tumours. Liver transplantation may be another treatment modality in selected cases.
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| 29. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Management of disseminated midgut carcinoid tumours.
- 1991
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Ingår i: Digestion. - 0012-2823. ; 49:2, s. 78-96
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Tidskriftsartikel (refereegranskat)abstract
- Forty-one patients with disseminated midgut carcinoid tumours were treated over a 6-year period according to a strict programme including primary surgical treatment. In 10 patients, a total remission of the disease was obtained. Patients with bilobar hepatic disease had ischaemic treatment of their liver metastases by hepatic arterial embolisation after primary surgical and medical treatment (low dose octreotide). Thus, by combining surgical, radiological and medical treatment modalities, we wanted to offer these patients optimal palliation. This treatment programme resulted in good symptomatic relief in all patients accompanied by a marked reduction in 5-hydroxyindoleacetic acid (5-HIAA) levels. At recurrence of symptoms in combination with rising 5-HIAA levels, embolisation was repeated. Ten of the treated patients have deceased during the observation period, but only 5 from their carcinoid disease.
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| 30. |
- Friman, Styrbjörn, 1948, et al.
(författare)
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Hepatic clearance of polyethylene glycol 900 and mannitol in the pig.
- 1988
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Ingår i: Digestion. - 0012-2823. ; 39:3, s. 172-80
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Tidskriftsartikel (refereegranskat)abstract
- Fluid phase markers like erythritol and mannitol have been used to study canalicular bile secretion in the liver. It has recently been suggested that these molecules cross the ductular epithelium and thereby their biliary clearance may underestimate the canalicular bile flow. In the present study, the hepatic clearance of polyethylene glycol 900 (PEG 900), a fluid phase marker that has been used in studies of the kidney, was compared to the clearance of mannitol in the pig. We found that the hepatic clearance of PEG 900 exceeded that of mannitol by a factor of 55. After intravenous bolus injections, both mannitol and PEG 900 appeared within 1 min in bile while significant proportions of inulin were seen only after 7 min. The hepatic clearances of both mannitol and PEG 900 positively correlated to the bile acid secretion rate and were not affected by secretin infusion. The high hepatic clearance of PEG 900 compared to mannitol may be explained by a higher fluid flux into the canaliculi than previously estimated and a continuous ductular reabsorption of fluid and mannitol. Another possibility is an active transcellular vesicular transport of this molecule--an explanation that is not supported by the immediate appearance of PEG 900 in bile following an intravenous bolus injection nor by the finding that hepatic clearance of labeled PEG was not affected by a load of unlabeled marker.
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| 31. |
- Kölby, Lars, 1963, et al.
(författare)
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Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors.
- 1998
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Ingår i: Digestion. - 0012-2823. ; 59:2, s. 160-6
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Tidskriftsartikel (refereegranskat)abstract
- A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MelmAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1-5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.
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