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| 2. |
- Lepsenyi, Mattias, et al.
(författare)
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Self-expanding metal stents in malignant colonic obstruction: experiences from Sweden.
- 2011
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute surgery in the management of malignant colonic obstruction is associated with high morbidity and mortality. The use of self-expanding metal stents (SEMS) is an alternative method of decompressing colonic obstruction. SEMS may allow time to optimize the patient and to perform preoperative staging, converting acute surgery into elective. SEMS is also proposed as palliative treatment in patients with contraindications to open surgery. Aim: To review our experience of SEMS focusing on clinical outcome and complications. The method used was a review of 75 consecutive trials at SEMS on 71 patients based on stent-protocols and patient charts. FINDINGS: SEMS was used for palliation in 64 (85%) cases and as a bridge to surgery in 11 (15%) cases. The majority of obstructions, 53 (71%) cases, were located in the recto-sigmoid. Technical success was achieved in 65 (87%) cases and clinical decompression was achieved in 60 (80%) cases. Reasons for technical failure were inability to cannulate the stricture in 5 (7%) cases and suboptimal SEMS placement in 3 (4%) cases. Complications included 4 (5%) procedure-related bowel perforations of which 2 (3%) patients died in junction to post operative complications. Three cases of bleeding after SEMS occurred, none of which needed invasive treatment. Five of the SEMS occluded. Two cases of stent erosion were diagnosed at the time of surgery. Average survival after palliative SEMS treatment was 6 months. CONCLUSION: Our results correspond well to previously published data and we conclude that SEMS is a relatively safe and effective method of treating malignant colonic obstruction although the risk of SEMS-related perforations has to be taken into account.
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- Zhang, Su, et al.
(författare)
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NFAT regulates neutrophil recruitment, systemic inflammation and T-cell dysfunction in abdominal sepsis.
- 2014
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Ingår i: Infection and Immunity. - 1098-5522. ; 82:8, s. 3275-3288
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Tidskriftsartikel (refereegranskat)abstract
- The signaling mechanisms regulating neutrophil recruitment, systemic inflammation and T-cell dysfunction in polymicrobial sepsis are not clear. This study explored the potential involvement of the calcium/calcineurin-dependent transcription factor, nuclear factor of activated T-cells (NFAT) in abdominal sepsis. Cecal ligation and puncture (CLP) triggered NFAT-dependent transcriptional activity in the lung, spleen, liver and aorta in NFAT-luciferase reporter mice. Treatment with the NFAT inhibitor A-285222 prior to CLP completely prevented sepsis-induced NFAT activation in all these organs. Inhibition of NFAT activity reduced sepsis-induced formation of CXCL1, CXCL2 and CXCL5 chemokines and edema as well as neutrophil infiltration in the lung. Notably, NFAT inhibition efficiently reduced the CLP-evoked increases in HMBG1, IL-6 and CXCL5 levels in plasma. Moreover, administration of A-285222 restored sepsis-induced T-cell dysfunction, as evidenced by markedly decreased apoptosis and restored proliferative capacity of CD4 T-cells. Along these lines, treatment with A-285222 restored IFN-γ and IL-4 levels in the spleen, which were markedly reduced in septic mice. CLP-induced formation of regulatory T-cells (CD4(+)CD25(+)Foxp3(+)) in the spleen was also abolished in A-285222-treated animals. Altogether, these novel findings suggest that NFAT is a powerful regulator of pathological inflammation and T-cell immune dysfunction in abdominal sepsis. Thus, our data suggest that NFAT signaling might be a useful target to protect against respiratory failure and immunosuppression in patients with sepsis.
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| 4. |
- Hartman Magnusson, Hannes, et al.
(författare)
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P-selectin mediates neutrophil rolling and recruitment in acute pancreatitis
- 2012
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 99, s. 246-255
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Tidskriftsartikel (refereegranskat)abstract
- Background: The adhesive mechanisms regulating leucocyte-endothelium interactions in the pancreas remain elusive, but selectins may play a role. This study examined the molecular mechanisms mediating leucocyte rolling along the endothelium in the pancreas and the therapeutic potential of targeting the rolling adhesive interaction in acute pancreatitis (AP). Methods: Pancreatitis was induced by retrograde infusion of 5 per cent sodium taurocholate into the pancreatic duct, repeated intraperitoneal administration of caerulein (50 μg/kg) or intraperitoneal administration of L-arginine (4 g/kg) in C57BL/6 mice. A control and a monoclonal antibody against P-selectin were administered before and after induction of AP. Serum and tissue were sampled to assess the severity of pancreatitis, and intravital microscopy was used to study leucocyte rolling. Results: Taurocholate infusion into the pancreatic duct increased the serum level of trypsinogen, trypsinogen activation, pancreatic neutrophil infiltration, macrophage inflammatory protein (MIP) 2 formation and tissue damage. Immunoneutralization of P-selectin decreased the taurocholate-induced increase in serum trypsinogen (median (range) 17·35 (12·20- 30·00) versus 1·55 (0·60-15·70) μg/l; P = 0·017), neutrophil accumulation (4·00 (0·75-4·00) versus 0·63 (0-3·25); P = 0·002) and tissue damage, but had no effect on MIP-2 production (14·08 (1·68-33·38) versus 3·70 (0·55-51·80) pg/mg; P = 0·195) or serum trypsinogen activating peptide level (1·10 (0·60-1·60) versus 0·45 (0-1·80) μg/l; P = 0·069). Intravital fluorescence microscopy revealed that anti-P-selectin antibody inhibited leucocyte rolling completely in postcapillary venules of the inflamed pancreas. Conclusion: Inhibition of P-selectin protected against pancreatic tissue injury in experimental pancreatitis. Targeting P-selectin may be an effective strategy to ameliorate inflammation in AP. © 2011 British Journal of Surgery Society Ltd.
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| 5. |
- Klintman, Daniel, et al.
(författare)
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Important role of p-selectin for leukocyte recruitment, hepatocellular injury, and apoptosis in endotoxemic mice.
- 2004
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Ingår i: Clinical and Diagnostic Laboratory Immunology. - 1071-412X. ; 11:1, s. 56-62
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte recruitment in the liver includes a two-step procedure in which selectin-dependent leukocyte rolling is a prerequisite for subsequent CD18-dependent leukocyte firm adhesion in postsinusoidal venules. However, the roles of the individual selectins in leukocyte rolling and adhesion, hepatocellular injury, and apoptosis remain elusive. Therefore, we examined the pathophysiological role of P-, E-, and L-selectin in male C57BL/6 mice challenged with lipopolysaccharide (LPS) and D-galactosamine (Gal) by use of intravital microscopy of the liver microcirculation. In control animals, administration of LPS-Gal provoked reproducible hepatic damage, including marked increases of leukocyte recruitment, liver enzymes, and hepatocyte apoptosis and reduced sinusoidal perfusion. Interestingly, pretreatment with an anti-P-selectin antibody (RB40.34) markedly reduced leukocyte rolling and firm adhesion by 65 and 71%, respectively. Moreover, interference with P-selectin function significantly improved sinusoidal perfusion and reduced the increase in liver enzymes by 49 to 84% in endotoxemic mice. Moreover, the activity of caspase-3 and the number of apoptotic hepatocytes were significantly reduced by 55 and 54%, respectively, in RB40.34-treated animals. In contrast, administration of an anti-E-selectin antibody (10E9.6) and an anti-L-selectin antibody (Mel-14) did not protect against endotoxin-induced leukocyte responses or hepatic injury. In conclusion, our novel findings document a principal role of P-selectin in mediating leukocyte rolling, a precondition to the subsequent firm adhesion of leukocytes in liver injury. Furthermore, our novel data demonstrate that inhibition of P-selectin function reduces hepatocellular injury and apoptosis, suggesting a causal relationship between leukocyte recruitment on one hand and hepatocellular injury and apoptosis on the other hand. Based on these findings, it is suggested that P-selectin may be an important therapeutic target in endotoxin-induced liver injury.
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| 7. |
- Zawadzki, Antoni, et al.
(författare)
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Verapamil Inhibits L-type Calcium Channel Mediated Apoptosis in Human Colon Cancer Cells.
- 2008
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Ingår i: Diseases of the Colon & Rectum. - : Ovid Technologies (Wolters Kluwer Health). - 0012-3706. ; 51, s. 1696-1702
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Treatment with calcium channel blockers have been associated with increased colon cancer mortality in epidemiologic studies. We examined the potential expression and function of calcium channels in two human colon cancer cell lines. METHODS: Both primary (collected at operation) and commercially-available human colon cancer cell lines were used. The colon cancer cells were incubated with a calcium channel blocker (verapamil) and a calcium channel agonist (BayK 8644) at clinically relevant concentrations. L-type calcium channel mRNA was determined by reverse-transcription polymerase chain reaction. Intracellular calcium ion levels were measured with fluorometry and apoptosis with flow cytometry. RESULTS: Both types of cells expressed L-type calcium channel mRNA, comprising an alpha-1D and a beta-3 subunit, whereas the cells were negative for N-type and P-type channels. The selective calcium channel agonist (BayK 8644), dose-dependently increased intracellular calcium ion levels and the level of apoptosis in primary human colon cancer cells. Pretreatment with verapamil completely abolished both calcium channel agonist-induced influx of calcium and apoptosis in these cells. CONCLUSIONS: These data demonstrate that human colon cancer cells express L-type calcium channels that mediate calcium influx and apoptosis, which warrants further studies to determine whether calcium channel blockers may promote colon cancer growth.
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| 8. |
- Muhammad, Asad, et al.
(författare)
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Platelets support pulmonary recruitment of neutrophils in abdominal sepsis
- 2009
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Ingår i: Critical Care Medicine. - 1530-0293. ; 37:4, s. 1389-1396
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction. Measurements and Main Results. CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1. Conclusions: These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis. (Crit Care Med 2009; 37:1389-1396)
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| 9. |
- Rönnow, Carl-Fredrik, et al.
(författare)
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Endoscopic submucosal dissection of 301 large colorectal neoplasias : outcome and learning curve from a specialized center in Europe
- 2018
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Ingår i: Endoscopy International Open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 6:11, s. 1340-1348
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Tidskriftsartikel (refereegranskat)abstract
- Background and study aims Endoscopic submucosal dissection (ESD) allows en bloc resection of large colorectal lesions but ESD experience is limited outside Asia. This study evaluated implementation of ESD in the treatment of colorectal neoplasia in a Western center. Patients and methods Three hundred and one cases of colorectal ESD (173 rectal and 128 colonic lesions) were retrospectively evaluated in terms of outcome, learning curve and complications. Results Median size was 4 cm (range 1 - 12.5). En bloc resection was achieved in 241 cases amounting to an en bloc resection rate of 80 %. R0 resection was accomplished in 207 cases (69 %), RX and R1 were attained in 83 (27 %) and 11 (4 %) cases, respectively. Median time was 98 min (range 10 - 588) and median proficiency was 7.2 cm 2 /h. Complications occurred in 24 patients (8 %) divided into 12 immediate perforations, five delayed perforations, one immediate bleeding and six delayed bleedings. Six patients (2 %), all with proximal lesions, had emergency surgery. Two hundred and four patients were followed up endoscopically and median follow-up time was 13 months (range 3 - 53) revealing seven recurrences (3 %). En bloc rate improved gradually from 60 % during the first period to 98 % during the last period. ESD proficiency significantly improved between the first study period (3.6 cm 2 /h) and the last study period (10.8 cm 2 /h). Conclusions This study represents the largest material on colorectal ESD in the west and shows that colorectal ESD can be implemented in clinical routine in western countries after appropriate training and achieve a high rate of en bloc and R0 resection with a concomitant low incidence of complications. ESD of proximal colonic lesions should be attempted with caution during the learning curve because of higher risk of complications.
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| 10. |
- Rönnow, Carl Fredrik, et al.
(författare)
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Forceps Biopsies Are Not Reliable in the Workup of Large Colorectal Lesions Referred for Endoscopic Resection : Should They Be Abandoned?
- 2019
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Ingår i: Diseases of the Colon and Rectum. - 0012-3706. ; 62:9, s. 1063-1070
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Biopsies are routinely obtained in the workup of large colorectal polyps before endoscopic resection. OBJECTIVE: This study aimed to examine how reliable biopsies are in terms of reflecting the true histopathology of large colorectal polyps, in the clinical routine. DESIGN: This is a retrospective study. SETTINGS: Data from patients undergoing polypectomy of large colorectal polyps at the endoscopy unit, Skåne University Hospital Malmö, between January 2014 and December 2016 were scrutinized. PATIENTS: A total of 485 colorectal lesions were biopsied within 1 year before complete endoscopic removal. Biopsy-obtained specimens were compared with completely resected specimens in terms of concordance and discordance and if the final result was upgraded or downgraded. MAIN OUTCOME MEASURES: The primary outcome measured was the concordance between biopsy-obtained specimens and completely resected specimens. RESULTS: Median lesion size was 3 cm (range 1-11). In 189 cases (39%), biopsies did not provide a correct dysplastic grade compared with final pathology after complete resection. One hundred forty-three cases (29%) and 46 cases (9%) were upgraded and downgraded. The percentage of cases with discordant biopsy results was 40% in cases with 1 biopsy taken and 38% in cases where multiple biopsies had been sampled. Time from biopsy to complete resection did not influence the erroneous outcome of biopsies. Notably, the percentage of discordant biopsy results was 37% and 35% in lesions measuring 1 to 2 cm and 2 to 4 cm. However, this percentage increased to 48% in colorectal lesions larger than 4 cm. LIMITATIONS: This study was designed to reflect the clinical routine, the number of biopsies obtained and forceps technique were hence not standardized, which constitutes a limitation. CONCLUSIONS: This study demonstrates that cancer-negative forceps biopsies of large colorectal polyps, referred for endoscopic resection, are not reliable. Considering that endoscopic resection of lesions containing superficial cancer is plausible, the clinical value of forceps biopsies in lesions suitable for endoscopic resection is questionable. See Video Abstract at http://links.lww.com/DCR/A984. LAS BIOPSIAS CON FÓRCEPS NO SON CONFIABLES EN EL ESTUDIO DE LAS LESIONES COLORRECTALES GRANDES REFERIDAS PARA RESECCIÓN ENDOSCÓPICA: ¿DEBERÍAN ABANDONARSE?: Las biopsias se obtienen de forma rutinaria en el estudio de pólipos colorrectales grandes previo a resección endoscópica. OBJETIVO: Analizar que tan confiables son las biopsias en cuanto a reflejar la verdadera histopatología de los pólipos colorrectales grandes, en la rutina clínica. DISEÑO:: Este es un estudio retrospectivo. AJUSTES: Los datos de pacientes sometidos a polipectomía de pólipos colorrectales grandes en la unidad de endoscopia, en Skåne University Hospital Malmö, entre enero de 2014 y diciembre de 2016 fueron examinados. PACIENTES: Un total de 485 lesiones colorrectales se biopsiaron dentro de un año antes de la resección endoscópica completa. Las muestras obtenidas mediante biopsia se compararon con las muestras completas resecadas en términos de concordancia y discordancia, y si el resultado final ascendió o disminuyó de categoría. PRINCIPALES MEDIDAS DE RESULTADO: Concordancia entre muestras obtenidas mediante biopsia y muestras completamente resecadas. RESULTADOS: La mediana de tamaño de lesiones fue de 3 cm (rango 1-11). En 189 casos (39%) las biopsias no proporcionaron un grado de displasia correcto en comparación con la patología final después de la resección completa. 143 casos (29%) y 46 casos (9%) ascendieron y descendieron de categoría, respectivamente. El porcentaje de casos con resultados de biopsia discordantes fue del 40% en los casos con una sola biopsia tomada y del 38% en los casos en los que se tomaron múltiples biopsias. El tiempo desde la biopsia hasta la resección completa no influyó en el resultado erróneo de las biopsias. Notablemente, el porcentaje de resultados de biopsia discordantes fue de 37% y 35% en lesiones que midieron 1-2 cm y 2-4 cm, respectivamente. Sin embargo, este porcentaje aumentó a 48% en lesiones colorrectales mayores de 4 cm. LIMITACIONES: Este estudio se diseñó para reflejar la rutina clínica, el número de biopsias obtenidas y la técnica de fórceps no fueron estandarizadas, lo que constituye una limitación. CONCLUSIONES: Este estudio demuestra que las biopsias con fórceps negativas a cáncer, de pólipos colorrectales grandes referidas para resección endoscópica, no son confiables. Teniendo en cuenta que la resección endoscópica de lesiones que contienen cáncer superficial es posible, el valor clínico de las biopsias con fórceps en lesiones aptas para la resección endoscópica es cuestionable. Vea el Resumen en video en http://links.lww.com/DCR/A984.
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