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4.
Br J Surg ; 107(1): 121-130, 2020 01.
Article in English | MEDLINE | ID: mdl-31802481

ABSTRACT

BACKGROUND: Transanal total mesorectal excision (TaTME) for rectal cancer has emerged as an alternative to the traditional abdominal approach. However, concerns have been raised about local recurrence. The aim of this study was to evaluate local recurrence after TaTME. Secondary aims included postoperative mortality, anastomotic leak and stoma rates. METHODS: Data on all patients who underwent TaTME were recorded and compared with those from national cohorts in the Norwegian Colorectal Cancer Registry (NCCR) and the Norwegian Registry for Gastrointestinal Surgery (NoRGast). Kaplan-Meier estimates were used to compare local recurrence. RESULTS: In Norway, 157 patients underwent TaTME for rectal cancer between October 2014 and October 2018. Three of seven hospitals abandoned TaTME after a total of five procedures. The local recurrence rate was 12 of 157 (7·6 per cent); eight local recurrences were multifocal or extensive. The estimated local recurrence rate at 2·4 years was 11·6 (95 per cent c.i. 6·6 to 19·9) per cent after TaTME compared with 2·4 (1·4 to 4·3) per cent in the NCCR (P < 0·001). The adjusted hazard ratio was 6·71 (95 per cent c.i. 2·94 to 15·32). Anastomotic leaks resulting in reoperation occurred in 8·4 per cent of patients in the TaTME cohort compared with 4·5 per cent in NoRGast (P = 0·047). Fifty-six patients (35·7 per cent) had a stoma at latest follow-up; 39 (24·8 per cent) were permanent. CONCLUSION: Anastomotic leak rates after TaTME were higher than national rates; local recurrence rates and growth patterns were unfavourable.


ANTECEDENTES: La resección total del mesorrecto transanal (transanal total mesorectal excision, TaTME) para el cáncer de recto se ha propuesto como una alternativa al abordaje abdominal tradicional. Sin embargo, la recidiva local (local recurrence, LR) después de este procedimiento es motivo de preocupación. El objetivo de este estudio fue evaluar la LR en pacientes operados mediante TaTME. Los objetivos secundarios incluyeron la mortalidad postoperatoria, las fugas anastomóticas y el porcentaje de estomas. MÉTODOS: Se registraron los datos de todos los pacientes operados mediante TaTME y se compararon con las cohortes nacionales del Registro Noruego de Cáncer Colorrectal (Norwegian Colorectal Cancer Registry, NCCR) y del Registro Noruego de Cirugía Gastrointestinal (Norwegian Registry for Gastrointestinal Surgery, NoRGast) utilizando estimaciones de Kaplan-Meier y la prueba de log-rank para comparar curvas de LR. RESULTADOS: En Noruega, 157 pacientes se sometieron a TaTME por cáncer de recto entre octubre de 2014 y octubre de 2018. Tres de siete hospitales abandonaron el TaTME después de un total de cinco procedimientos. La LR observada fue 12/157 (7,6%), siendo ocho de ellas multifocales o extensas. La tasa estimada de LR a 2,4 años fue de 11,6 % (i.c. del 95% 6,6 a 19,9) versus 2,4 % (1,4 a 4,3) en el NCCR (log rank P < 0,001). El cociente de riesgos instantáneos (hazard ratio, HR) ajustado fue 6,7 (i.c. del 95% 2,9 a 15,3). Las fugas anastomóticas que precisaron una reintervención después de TaTME ocurrieron en un 8,4% versus 4,5% en el registro NoRGast (P = 0,047). Cincuenta y seis pacientes (35,7%) tenían un estoma en el último seguimiento; 39 (24,8%) eran permanentes. CONCLUSIÓN: Las tasas de fuga anastomótica tras una TaTME fueron más altas que los datos nacionales con tasas de LR y patrones de crecimiento desfavorables.


Subject(s)
Neoplasm Recurrence, Local/mortality , Rectal Neoplasms/surgery , Transanal Endoscopic Surgery/adverse effects , Aged , Anastomotic Leak/etiology , Anastomotic Leak/mortality , Enterostomy/mortality , Enterostomy/statistics & numerical data , Female , Humans , Intraoperative Complications/etiology , Intraoperative Complications/mortality , Male , Middle Aged , Norway/epidemiology , Patient Safety , Proctectomy/mortality , Proctectomy/statistics & numerical data , Rectal Neoplasms/mortality , Registries , Transanal Endoscopic Surgery/mortality
5.
Surg Endosc ; 33(9): 2821-2833, 2019 09.
Article in English | MEDLINE | ID: mdl-30413929

ABSTRACT

BACKGROUND: To describe the real burden of major complications after elective surgery for colon cancer in Norway, and to assess which predictors that are significantly associated with the short-term outcome. METHODS: An observational, multi-centre analysis of prospectively registered colon resections registered into the Norwegian Registry for Gastrointestinal Surgery, NoRGast, between January 2014 and December 2016. A propensity score-adjusted subgroup analysis for surgical access groups was attempted, with laparoscopic resections grouped as intention-to-treat. RESULTS: Out of 1812 resections, 14.0% of patients experienced a major complication within 30 days following surgery. The over-all reoperation rate was 8.7%, and rate of reoperation for anastomotic leak was 3.8%. Twenty patients (1.1%) died within 30 days after surgery. Higher age was not a significant predictor of major complications, including 30-day mortality. After correction for all co-variables, open access surgery was associated with higher rates of major complications (OR 1.67 (CI 1.22-2.29), p = 0.002), higher 30-day mortality (OR 4.39 (CI 1.19-16.13) p = 0.026) and longer length-of-stay (HR 0.58 (CI 0.52-0.65) p < 0.001). CONCLUSIONS: Our results indicate a low complication burden and high rate of uneventful patient journeys after elective surgery for colon cancer in Norway. Age was not associated with higher morbidity or mortality rates. Open access surgery was associated with an inferior short-term outcome.


Subject(s)
Colectomy , Colonic Neoplasms/surgery , Elective Surgical Procedures , Laparoscopy , Postoperative Complications , Aged , Colectomy/adverse effects , Colectomy/methods , Colonic Neoplasms/epidemiology , Elective Surgical Procedures/adverse effects , Elective Surgical Procedures/methods , Female , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Male , Middle Aged , Norway/epidemiology , Outcome and Process Assessment, Health Care , Postoperative Complications/etiology , Postoperative Complications/mortality , Registries/statistics & numerical data , Reoperation/statistics & numerical data
6.
Scand J Surg ; 107(3): 201-207, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29628007

ABSTRACT

BACKGROUND AND AIMS: There is an increasing demand for high-quality data for the outcome of health care. Diseases of the gastro-intestinal tract involve large patient groups often presenting with serious or life-threatening conditions. Complications may affect treatment outcomes and lead to increased mortality or reduced quality of life. A continuous, risk-adjusted monitoring of major complications is important to improve the quality of health care to patients undergoing gastrointestinal resections. We present the development of the Norwegian Registry for Gastrointestinal Surgery, a national registry for colorectal, upper gastrointestinal, and hepato-pancreato-biliary resections in Norway. MATERIALS AND METHODS: A narrative and qualitative presentation of the development and current state of the registry. RESULTS: We present the variables and the analysis tools and provide examples for the potential in quality improvement and research. Core characteristics include a strictly limited set of variables to reflect important risk factors, the procedure performed, and the clinical outcomes. CONCLUSION: A registry with the potential to present complete national cohort data is a powerful tool for quality improvement and research.


Subject(s)
Digestive System Diseases/epidemiology , Digestive System Diseases/surgery , Digestive System Surgical Procedures/statistics & numerical data , Quality Improvement/statistics & numerical data , Registries/statistics & numerical data , Humans , Norway/epidemiology
7.
Colorectal Dis ; 18(1): 67-72, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26201935

ABSTRACT

AIM: Pathological complete response (ypCR) after neoadjuvant treatment for rectal cancer is associated with favourable survival and a low rate of local recurrence. The aim of the study was to assess the incidence of ypCR among patients with advanced rectal cancer treated with neoadjuvant chemoradiotherapy and curative resection and to explore factors associated with survival. METHOD: From 2000 to 2009, 1384 patients enrolled in the national population- based colorectal cancer registry of Norway with advanced T3 and T4 rectal cancer with N0-2, M0 received neoadjuvant long-course (chemo)radiation. The duration of follow-up was a median of 5 years. RESULTS: ypCR was achieved in 147 (10.6%) patients. The estimated 5-year overall survival rate was 87% (confidence interval ± 5.4) among ypCR and 67% among non-ypCR (confidence interval ± 2.7) (P < 0.0001). Distant metastasis developed in 12 (8%) of 147 and 328 (26.5%) of 1237 patients respectively (P < 0.001). In a Cox proportional hazards ratio model the effect of ypCR on survival was adjusted for age [hazard ratio (HR) 1.056, P = 0.0001], metachronous metastasis (HR 4.7, P = 0.0001), local recurrence (HR 4.3, P = 0.0001) and surgical procedure (HR 1.48, P = 0.0001). The independent effect of ypCR (HR 0.65, P = 0.041) on survival almost disappeared compared with the univariate analysis. CONCLUSION: The rate of ypCR in advanced rectal cancer was about 10%. This phenomenon seems to occur in tumours with a low risk of metastasizing. The contribution of neoadjuvant therapy to ypCR on survival was small or absent.


Subject(s)
Neoadjuvant Therapy , Radiotherapy , Rectal Neoplasms/radiotherapy , Rectum/surgery , Registries , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Chemoradiotherapy , Cohort Studies , Digestive System Surgical Procedures , Female , Fluorouracil/therapeutic use , Humans , Male , Middle Aged , Neoplasm Staging , Norway , Proportional Hazards Models , Rectal Neoplasms/pathology , Rectum/pathology , Treatment Outcome , Young Adult
8.
Br J Surg ; 101(13): 1712-20, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25312592

ABSTRACT

BACKGROUND: Perioperative chemotherapy has become standard care for resectable gastric cancer. However, available evidence is based on a limited number of trials, and the outcomes in routine clinical practice and in unselected patients are scarcely reported. METHODS: The study included a consecutive series of patients with resectable gastric cancer treated between 2001 and 2011 in Central Norway. Before 2007, patients with resectable gastric cancer did not receive perioperative chemotherapy. Since 2007, medically fit patients with resectable gastric cancer and aged 75 years or less have been offered this. Response rates were evaluated by CT, and tolerability was assessed by the frequency of hospital admission, need for dose reduction or treatment discontinuation. The two time intervals were compared on an intention-to-treat basis for patients aged no more than 75 years for any impact on resection rates, surgical morbidity, postoperative mortality and long-term survival. RESULTS: About two-thirds (259) of the 419 patients registered were aged 75 years or less at diagnosis. Ninety-five of 136 patients in the later interval were eligible for chemotherapy, of whom 90 actually received the specified regimen, and 78 (87 per cent) were able to complete the preoperative course. Only 40 (44 per cent) completed all scheduled preoperative and postoperative cycles. Thirty-eight (43 per cent) of 89 evaluable patients showed a definite response on CT. Chemotherapy had no impact on postoperative morbidity or mortality. The 5-year survival rate on an intention-to-treat basis was 40·7 (95 per cent c.i. 30·7 to 50·7) per cent in the first interval, compared with 41·7 (31·5 to 51·9) per cent after the introduction of perioperative chemotherapy (P = 0·765). After adjustment for other risk factors, based on comparisons of the two time intervals, there were no differences in oncological outcomes with the use of perioperative chemotherapy. CONCLUSION: Perioperative chemotherapy was completed in less than half of the patients with resectable gastric cancer. An observed tumour response to chemotherapy did not translate into any long-term survival benefit compared with surgery alone.


Subject(s)
Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/surgery , Adenocarcinoma/drug therapy , Adult , Aged , Chemotherapy, Adjuvant , Female , Humans , Intraoperative Care/methods , Male , Middle Aged , Prospective Studies , Stomach Neoplasms/drug therapy , Treatment Outcome
9.
Thromb Haemost ; 112(6): 1277-87, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25183015

ABSTRACT

Activated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute coronary syndrome (ACS), its medical treatment, concomitant clinical or laboratory parameters, and predictive for the progression of coronary artery disease (CAD). In an observational study, the association of various factors with plasma concentrations of platelet chemokines and neutrophil mediators in 204 patients, either upon admission with ACS and 6 hours later or without ACS or CAD, was determined by multiple linear regression. Mediator release was further analysed after activation of blood with ACS-associated triggers such as plaque material. CXCL4, CXCL4L1, CCL5, MPO and azurocidin levels were elevated in ACS. CXCL4 and CCL5 but not CXCL4L1 or MPO were associated with platelet counts and CRP. CXCL4 (in association with heparin treatment) and MPO declined over 6 hours during ACS. Elevated CCL5 was associated with a progression of CAD. Incubating blood with plaque material, PAR1 and PAR4 activation induced a marked release of CXCL4 and CCL5, whereas CXCL4L1 and MPO were hardly or not altered. Platelet chemokines and neutrophil products are concomitantly elevated in ACS and differentially modulated by heparin treatment. CCL5 levels during ACS predict a progression of preexisting CAD. Platelet-derived products appear to dominate the inflammatory response during ACS, adding to the emerging evidence that ACS per se may promote vascular inflammation.


Subject(s)
Acute Coronary Syndrome/diagnosis , Blood Platelets/metabolism , Chemokines/blood , Inflammation Mediators/blood , Inflammation/diagnosis , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/genetics , Acute Coronary Syndrome/immunology , Aged , Anticoagulants/therapeutic use , Antimicrobial Cationic Peptides/blood , Biomarkers/blood , Blood Platelets/drug effects , Blood Platelets/immunology , Blood Proteins , Carrier Proteins/blood , Case-Control Studies , Chemokine CCL5/blood , Chemokine CCL5/genetics , Chemokines/genetics , Disease Progression , Dose-Response Relationship, Drug , Female , Heparin/therapeutic use , Humans , Inflammation/blood , Inflammation/immunology , Linear Models , Male , Middle Aged , Neutrophils/drug effects , Neutrophils/immunology , Neutrophils/metabolism , Peroxidase/blood , Platelet Count , Polymorphism, Single Nucleotide , Predictive Value of Tests , Prognosis , Prospective Studies , Time Factors
10.
Br J Cancer ; 108(8): 1712-9, 2013 Apr 30.
Article in English | MEDLINE | ID: mdl-23558896

ABSTRACT

BACKGROUND: microRNAs (miRNAs) exist in blood in an apparently stable form. We have explored whether serum miRNAs can be used as non-invasive early biomarkers of colon cancer. METHODS: Serum samples from 30 patients with colon cancer stage IV and 10 healthy controls were examined for the expression of 375 cancer-relevant miRNAs. Based on the miRNA profile in this study, 34 selected miRNAs were measured in serum from 40 patients with stage I-II colon cancer and from 10 additional controls. RESULTS: Twenty miRNAs were differentially expressed in serum from stage IV patients compared with controls (P<0.01). Unsupervised clustering revealed four subgroups; one corresponding mostly to the control group and the three others to the patient groups. Of the 34 miRNAs measured in the follow-up study of stage I-II patients, 21 showed concordant expression between stage IV and stage I-II patient. Based on the profiles of these 21 miRNAs, a supervised linear regression analysis (Partial Least Squares Regression) was performed. Using this model we correctly assigned stage I-II colon cancer patients based on miRNA profiles of stage IV patients. CONCLUSION: Serum miRNA expression profiling may be utilised in early detection of colon cancer.


Subject(s)
Colonic Neoplasms/blood , Colonic Neoplasms/genetics , MicroRNAs/blood , Case-Control Studies , Colonic Neoplasms/pathology , Female , Humans , Linear Models , Male , Middle Aged , Neoplasm Staging
11.
J Surg Oncol ; 107(7): 752-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23335125

ABSTRACT

OBJECTIVES: To evaluate the outcomes among patients treated for gastric adenocarcinoma in a referral hospital, and to identify possible trends during the last decade. METHODS: All patients evaluated for gastric adenocarcinoma during the period 1999-2009 were included. RESULTS: Of 397 patients, 52% were curatively resected. Crude 5-year survival for the first 6 years period was 38.7% (CI 29.5-47.9), for the last 5 years, 49.2% (CI 38.8-59.6). Time period (P = 0.013), age (P < 0.001) and disease stage (P < 0.001), were significant predictors of long-term survival rates. Among curatively resected, in-hospital mortality was reduced from 8.5% in the first period to 2.0% in the last one (P = 0.037). There was a significant increase in the use of primary stents from the first to the last period (P = 0.006), paralleled by a significant reduction in the number of explorative laparotomies or bypass procedures (P < 0.001). CONCLUSIONS: During the last decade, long-term survival rates improved among patients curatively resected for gastric adenocarcinoma, and in-hospital mortality was substantially reduced. For patients in a non-curative situation, there was a significant shift from explorative laparotomies or bypass procedures to primary use of stents.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gastrectomy , Stomach Neoplasms/therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Treatment Outcome
12.
Endoscopy ; 44(10): 934-9, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22752890

ABSTRACT

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease, which typically affects middle-aged men and is frequently associated with inflammatory bowel disease. Early recognition and accurate diagnosis remains a clinical challenge. Invasive diagnostic procedures, such as endoscopic retrograde cholangiography or liver biopsy are needed when magnetic resonance cholangiopancreatography remains inconclusive. As these procedures are associated with significant risks, the current study sought to determine whether endoscopic ultrasound (EUS) of the biliary tract is a useful diagnostic tool in cases of suspected PSC. PATIENTS AND METHODS: In a prospective pilot study, 138 patients presenting with chronic cholestatic hepatopathy were screened and 32 patients with possible PSC were evaluated further. In addition to all routine measures, EUS was included in the diagnostic work-up.  The following parameters were evaluated and compared with the definitive diagnosis: wall thickening ( ≥ 1.5  mm), irregular wall structure, significant changes of caliber of the common bile duct, and perihilar lymphadenopathy. RESULTS: In the 138 patients screened, a PSC prevalence of 13 % was found. Of the 32 patients included in the study, 17 had large-duct PSC diagnosed. When two of the aforementioned four parameters showed PSC-like features, sensitivity and specificity of predicting PSC were 76.4 % and 100 %, with positive and negative predictive values of 100 % and 79 %, respectively. In four patients presenting with strictly intrahepatic disease, EUS was not diagnostic. CONCLUSIONS: EUS proved to be a valuable tool in suspected PSC and accurately predicted extrahepatic disease. EUS should be evaluated further as an early procedure in routine diagnostic measurements. This approach promises a significant improvement in disease detection as well as a reduction in high risk invasive procedures.


Subject(s)
Cholangitis, Sclerosing/diagnostic imaging , Endosonography/methods , Adult , Biopsy , Cholangiopancreatography, Endoscopic Retrograde , Cholangiopancreatography, Magnetic Resonance , Comorbidity , Female , Humans , Likelihood Functions , Male , Middle Aged , Pilot Projects , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Statistics, Nonparametric
13.
Colorectal Dis ; 12(10 Online): e283-90, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20345969

ABSTRACT

AIM: There are conflicting reports regarding long term function after ileal pouch-anal anastomosis (IPAA). The aim of the present prospective study was to investigate the influence of duration as an independent factor on long-term function results. METHOD: Between 1984 and 2007, 315 patients underwent IPAA and were followed by a standardised interview and endoscopy protocol. There were 1802 interviews. Two hundred and thirty-five patients had three or more visits and these data were analysed by Time-Series-Cross-Section multivariate regression analysis. The mean time follow up was 12 years and the mean interval between visits was 34.5 months. RESULTS: Mean frequency of defecation was 5.2 in the day and 0.55 at night. This did not change with time. Daytime and night incontinence occurred in 13% and 21%. There was no change in incontinence, urgency, soiling or perineal excoriation with time. After 24 years the cumulative incidence of pouchitis was 43.5%. Twenty patients had chronic pouchitis (6.3%). CONCLUSION: The interval from IPAA did not influence the long-term functional outcome.


Subject(s)
Colonic Pouches/physiology , Proctocolectomy, Restorative , Adolescent , Adult , Aged , Anal Canal/physiopathology , Anal Canal/surgery , Chronic Disease , Defecation/physiology , Fecal Incontinence/physiopathology , Female , Follow-Up Studies , Humans , Ileum/physiopathology , Ileum/surgery , Incidence , Intestinal Diseases/surgery , Male , Middle Aged , Pouchitis/epidemiology , Pouchitis/etiology , Proctocolectomy, Restorative/adverse effects , Prospective Studies , Regression Analysis , Time Factors , Young Adult
14.
Br J Cancer ; 102(3): 482-8, 2010 Feb 02.
Article in English | MEDLINE | ID: mdl-20051945

ABSTRACT

BACKGROUND: The aim of this study was to assess the performance of the Revised Bethesda Guidelines (RBG) and the accuracy of the Amsterdam II criteria (AM II) in identifying possible Lynch syndrome (LS) compared with the results of molecular tumour testing. METHODS: Tumours from 336 unselected colorectal cancer patients were analysed by three molecular tests (namely microsatellite instability (MSI), BRAF mutation and methylation of mismatch-repair genes), and patients were classified according to the RBG and AM II criteria. RESULTS: A total of 87 (25.9%) patients fulfilled the RBG for molecular tumour analyses (MSI and/or immunohistochemistry), and the AM II identified 8 (2.4%) patients as having possible LS. Molecular tests identified 12 tumours (3.6%) as probable LS. The RBG identified 6 of the 12 patients (sensitivity 50%), whereas 5 of the 8 patients who fulfilled the AM II criteria were not likely to be LS, based on molecular tests (predictive value of positive test, 38%). INTERPRETATION: Assuming a fairly high accuracy of molecular testing, the performance of the RBG in identifying patients with possible LS was poor, and the AM II criteria falsely identified a large proportion as having possible LS. This favours the use of molecular testing in the diagnosis of possible LS.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms/genetics , Aged , Aged, 80 and over , DNA Methylation , DNA-Binding Proteins/genetics , Female , Humans , Male , Microsatellite Instability , Middle Aged , Mutation , Practice Guidelines as Topic , Promoter Regions, Genetic , Prospective Studies , Proto-Oncogene Proteins B-raf/genetics
15.
Z Gastroenterol ; 48(1): 38-45, 2010 Jan.
Article in German | MEDLINE | ID: mdl-20072995

ABSTRACT

Liver fibrosis is the common sequel of chronic liver diseases and is associated with high morbidity and mortality in affected patients. In recent years, the contribution of chemokines and their receptors to liver fibrosis has been delineated. Chemokines are a family of chemotactic and immunomodulatory molecules that act through different G-protein coupled receptors on target cells. Apart from their classical function of regulating immune cell recruitment during chronic liver injury, chemokines can directly affect the function of hepatic stellate cells within the liver. Up to now, nine of the 19 known chemokine receptors have been characterised on stellate cells. Stimulation of most of these receptors with specific ligands leads to increased migration and proliferation of stellate cells, suggesting predominantly profibrotic effects of chemokines. The only chemokine receptor with potential antifibrotic effects identified so far is CXCR3. Notably, hepatic stellate cells are not only a target but also a source of chemokines which contributes to the direct interaction between stellate cells and other cells during fibrogenesis. The further characterisation of this interaction will yield new therapeutic options for the treatment of chronic liver diseases. In this respect chemokines are a valuable target as oral chemokine receptor antagonists have already been licensed for human use.


Subject(s)
Chemokines/physiology , Hepatic Stellate Cells/immunology , Liver Cirrhosis/immunology , Animals , Cell Movement/immunology , Cell Proliferation , Hepatitis C, Chronic/immunology , Humans , Mice , Receptors, CXCR3/physiology , Receptors, Chemokine/physiology , Signal Transduction/immunology
16.
Internist (Berl) ; 51(1): 14-20, 2010 Jan.
Article in German | MEDLINE | ID: mdl-19921111

ABSTRACT

Liver fibrosis results from chronic liver damage and is characterized by scarring of the liver parenchyma. Liver fibrosis can occur in all chronic liver diseases and shows progression towards liver cirrhosis in 20-40% of cases. The clinical presentation of liver fibrosis is usually unspecific. Therefore, most patients with liver fibrosis are identified by elevated liver enzymes during other medical examinations. The gold standard for quantification of liver fibrosis is percutaneous liver biopsy, but non-invasive markers (e. g. serum markers, transient elastography) have recently been evaluated to identify individuals with significant fibrosis. In case of fibrosis detection, medical therapies aim at stabilizing liver scarring or even at inducing the regression of fibrosis. Primarily this is achieved by etiology specific therapies of chronic liver diseases (e. g. antiviral therapy, immunosuppressive therapy etc.). However, in cases of failure of these specific therapies, non-specific interventions for fibrosis regression are actively being investigated. These treatment options are based on the growing molecular knowledge of fibrogenesis but are not yet available for routine clinical use.


Subject(s)
Immunosuppressive Agents/therapeutic use , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Humans
17.
Colorectal Dis ; 12(7 Online): e109-13, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19341399

ABSTRACT

OBJECTIVE: The long-term failure rate of ileal pouch-anal anastomosis (IPAA) is 10-15%. When salvage surgery is unsuccessful, most surgeons prefer pouch excision with conventional ileostomy, thus sacrificing 40-50 cm of ileum. Conversion of a pelvic pouch to a continent ileostomy (CI, Kock pouch) is an alternative that preserves both the ileal surface and pouch properties. The aim of the study was to evaluate clinical outcome after the construction of a CI following a failed IPAA. METHOD: During 1984-2007, 317 patients were operated with IPAA at St Olavs Hospital and evaluated for failure, treatment and outcome. Seven patients with IPAA failure had CI. Four patients with IPAA failure referred from other hospitals underwent conversion to CI and are included in the final analysis. RESULTS: Seven patients had a CI constructed from the transposing pelvic pouch and four had the pelvic pouch removed and a new continent pouch constructed from the distal ileum. Median follow up after conversion to CI was 7 years (0-17 years). Two CI had to be removed due to fistulae. One patient needed a revision of the nipple valve due to pouch loosening. At the end of follow-up, 8 of the 11 patients were fully continent. One patient with Crohn's disease had minor leakage. CONCLUSION: In patients with pelvic pouch failure, the possibility of conversion to CI should be presented to the patient as an alternative to pouch excision and permanent ileostomy. The advantage is the continence and possibly a better body image. Construction of a CI on a new ileal segment may be considered, but the consequences of additional small bowel loss and risk of malnutrition if the Kock pouch fails should be appraised.


Subject(s)
Colonic Diseases/surgery , Colonic Pouches/adverse effects , Ileostomy/methods , Proctocolectomy, Restorative/methods , Reoperation/methods , Adult , Female , Follow-Up Studies , Humans , Male , Proctocolectomy, Restorative/adverse effects , Retrospective Studies , Time Factors , Treatment Failure , Treatment Outcome
18.
Endoscopy ; 42(1): 22-7, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19899031

ABSTRACT

BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) has been developed as a new technique to differentiate tissue patterns in vivo. The aim of this study was to evaluate the diagnostic accuracy of NBI endoscopy with and without high magnification for the differentiation of neoplastic from non-neoplastic colorectal polyps. PATIENTS AND METHODS: Among 200 colorectal polyps from 131 patients, 100 lesions were classified according to vascular patterns by NBI endoscopy with high optical magnification and 100 lesions by high-definition endoscopy without high magnification. Additionally, the clarity of the vessel network was assessed. Histologic analysis was performed on all lesions. RESULTS: NBI endoscopy with high magnification resulted in a sensitivity of 92.1 % and a specificity of 89.2 % for the differentiation of neoplastic versus non-neoplastic lesions. This performance was statistically comparable to high-definition NBI endoscopy without high magnification, which showed a sensitivity of 87.9 % and specificity of 90.5 %. However, vessel network was significantly better visualized by NBI endoscopy with optical magnification compared with high-definition NBI endoscopy without high magnification. In comparison with NBI endoscopy, white-light endoscopy, with or without magnification, resulted in inferior discrimination between neoplastic and non-neoplastic polyps. CONCLUSION: The results demonstrate that the superior visibility of capillary vessels by the NBI technique allows the evaluation of colorectal lesions - based on the vascular patterns - with high diagnostic accuracy. In clinical routine, high-definition NBI endoscopy without high magnification may be used to sufficiently predict colorectal polyp histology, and high magnification can additionally facilitate visualization of vascular networks.


Subject(s)
Colonic Neoplasms/pathology , Colonic Polyps/classification , Colonic Polyps/pathology , Colonoscopy/methods , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Sensitivity and Specificity
19.
Colorectal Dis ; 11(7): 711-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19708089

ABSTRACT

AIM: To evaluate surgical workload and complications in patients who had undergone restorative proctocolectomy, through long-term follow-up in one single institution. METHOD: From 1984 to 2006, 304 consecutive patients underwent Ileal Pouch-Anal Anastomosis (IPAA). There were 182 stapled and 122 hand-sewn anastomoses. A protective loop ileostomy was established in 256 patients (84%), whereas 48 patients (16%) were without a covering stoma. RESULTS: Twenty-nine patients (10%) suffered from early anastomotic leakage. A protective stoma did not prevent early anastomotic dehiscence (P = 0.11) or the number of pelvic abscesses (P = 0.09). Early complications required 20 laparotomies with creation of a diverting stoma in nine patients. There were 16 (6%) complications related to closure of the loop ileostomy. Sixty-six patients needed an additional re-operation related to the IPAA procedure. There were 20 removals of pouches and three permanent diverting stomas. The estimated removal rate at 20 years of a functioning pouch was 11% (CI +/- 6). Altogether 100 (33%) patients had one or more surgical procedures, excluding dilations of anastomotic strictures and closing of a loop ileostomy. These 100 patients underwent 187 surgical procedures. The estimated rate of a first re-operation due to complications was 52% (CI +/- 16) in 20 years. Hand-sewn anastomoses had similar complications and failure rates as stapled anastomoses. CONCLUSIONS: More than half of patients operated with restorative proctocolectomy will need surgical intervention within 20 years and the failure rate is more than 10%. The high risk of complications and failure inherent in the procedure should not be ignored.


Subject(s)
Colonic Pouches/adverse effects , Proctocolectomy, Restorative/adverse effects , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Reoperation , Survival Analysis , Suture Techniques , Sutures , Young Adult
20.
Colorectal Dis ; 11(5): 456-61, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19508550

ABSTRACT

OBJECTIVE: The assessment of family history and medical data is crucial in identifying families with Lynch syndrome (LS). Among consecutive colorectal cancer (CRC) patients, we aimed at identifying all patients with a hereditary predisposition, and to study a possible discrepancy with assessments made by the responsible clinicians. METHOD: All consecutively diagnosed patients with CRC from two Norwegian hospitals were included, and information on family history was collected in a detailed interview. We assessed information in medical records, and tumours were examined for LS-associated histopathological features. RESULTS: Among 562 patients, there was no documentation of family history in 388 (69.0%) medical records, and in 174 (31.0%) patients, there was no clinical assessment of the information that was collected on family history. Based on detailed interviews and extended pathological examination, we found that 137 (24.4%) of the 562 patients could be classified as possible LS according to the Revised Bethesda Guidelines (RBG); and that 46 (33.6%) of these patients could be identified by family history alone. CONCLUSION: Family history and relevant information in patient records can identify patients with possible LS. However, clinicians often fail to include information on hereditary factors and to assess relevant data in medical records. Familial CRC is therefore not acknowledged, and genetic counselling is not offered.


Subject(s)
Colorectal Neoplasms/genetics , Documentation/statistics & numerical data , Family Health , Genetic Predisposition to Disease/genetics , Adult , Aged , Aged, 80 and over , Cohort Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Female , Genetic Predisposition to Disease/epidemiology , Humans , Male , Middle Aged , Norway , Practice Guidelines as Topic
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