RESUMEN
The authors examined the potential of the cyclooxygenase 2 (COX-2) inhibitor carprofen to reproducibly induce anastomotic leakage. In experiment 1, an anastomosis was constructed in both ileum and colon of 20 rats, and they were given carprofen (5 mg/kg subcutaneously every 24 hours) or buprenorphine (0.02 mg/kg subcutaneously every 12 hours). In another 20 rats an anastomosis was constructed in either ileum or colon, and all received carprofen (experiment 2). Animals were sacrificed after 3 days. In experiment 1, the ileal dehiscence rate was 60% in the carprofen group and 0% in the buprenorphine group (P = .0108). Colonic anastomoses in both groups remained patent. In experiment 2, the anastomotic leakage rate was 80% in ileum and 0% in colon. Thus, COX-2 inhibitors can severely interfere with intestinal healing, particularly in the ileum. Perioperative administration of carprofen yields a unique model for anastomotic leakage, which allows translational research on the effectiveness of perisuture line reinforcement.
Asunto(s)
Fuga Anastomótica/inducido químicamente , Carbazoles/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Íleon/cirugía , Dolor/tratamiento farmacológico , Dehiscencia de la Herida Operatoria/inducido químicamente , Analgésicos Opioides/farmacología , Fuga Anastomótica/patología , Fuga Anastomótica/fisiopatología , Animales , Buprenorfina/farmacología , Carbazoles/efectos adversos , Colágeno/metabolismo , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Modelos Animales de Enfermedad , Íleon/efectos de los fármacos , Íleon/metabolismo , Íleon/fisiopatología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Periodo Perioperatorio , Presión , Ratas , Ratas Wistar , Pérdida de Peso/efectos de los fármacosRESUMEN
INTRODUCTION: During bowel surgery, perioperative blood loss and hypotension can lead to transient intestinal ischemia. Recent preclinical studies reveal that the strength of intestinal anastomoses can be compromised after reperfusion. So far, this phenomenon has not been investigated in the very first days of healing when wound strength is lowest. MATERIAL AND METHOD: Ischemia was induced in rats by clamping both the superior mesenteric artery and ileal branches for 30 min. Immediately after declamping, anastomoses were constructed in both terminal ileum and descending colon. The same was done in control groups after sham-ischemia. Anastomotic bursting pressure and breaking strength were measured immediately after operation (day 0) and after 1, 2, or 3 days. Anastomotic hydroxyproline content, gelatinase activity, and histology were analyzed. RESULTS AND DISCUSSION: In ileal anastomoses, at day 1, both the breaking strength and bursting pressure were significantly (p < 0.05) lower in the ischemic group, while at day 2, this was the case for the bursting pressure only. In the colon, the bursting pressure in the ischemic group was lower at day 1. Anastomotic hydroxyproline content remained unchanged. Increased presence of the various gelatinase activities was found in ileum only at day 0 and in colon at days 1 and 2. Histological mucosal damage was found in ischemia-reperfusion groups. CONCLUSION: Transient mesenteric ischemia can negatively affect anastomotic strength during the very first days of healing, even if the tissue used for anastomotic construction looks vital.
Asunto(s)
Anastomosis Quirúrgica , Colon/cirugía , Íleon/cirugía , Isquemia/fisiopatología , Mesenterio/irrigación sanguínea , Cicatrización de Heridas/fisiología , Análisis de Varianza , Animales , Colon/irrigación sanguínea , Gelatinasas/metabolismo , Hidroxiprolina/metabolismo , Íleon/irrigación sanguínea , Masculino , Ratas , Ratas Wistar , Estrés MecánicoRESUMEN
BACKGROUND: Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) results in limited survival benefit and high morbidity and mortality rates in patients with peritoneal carcinomatosis (PC). Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound healing after CS need to be determined. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to CS and anastomotic construction only or followed by RIT or HIPEC. RIT consisted of 74 MBq (177)lutetium-labeled anti-CC531 antibody MG1. HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C during 60 minutes. Anastomotic and abdominal wall strength measurements were performed 3 and 5 days after surgery. RESULTS: At day 5, bursting pressure in ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT group, was lower (P < .01) than in the CS group. In the CS group, the colonic bursting site was more often outside the true anastomotic area (8 of 12 animals) than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall strength in the CS + HIPEC group was significantly (P < .01) lower, at both measuring points, than that in both the CS group and the CS + RIT group. There was no difference between the latter. CONCLUSION: As adjuvant to CS, HIPEC showed a decrease in anastomotic and abdominal wall wound strength in a model of PC of CRC, whereas RIT did not.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias del Colon/terapia , Hipertermia Inducida , Mitomicina/uso terapéutico , Neoplasias Peritoneales/terapia , Radioinmunoterapia , Cicatrización de Heridas , Pared Abdominal/fisiología , Pared Abdominal/cirugía , Anastomosis Quirúrgica , Animales , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Terapia Combinada , Modelos Animales de Enfermedad , Gelatinasas/metabolismo , Hidroxiprolina/metabolismo , Inyecciones Intraperitoneales , Intestinos/efectos de los fármacos , Intestinos/cirugía , Lutecio/uso terapéutico , Masculino , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/cirugía , Ratas , Ratas Endogámicas , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Selective cyclo-oxygenase 2 (COX-2) inhibitors are increasingly prescribed in the perioperative period. Recent recognition of a possible role for COX-2 in wound healing has raised concerns about the safety of their use in surgical practice. Therefore, the influence of celecoxib, a selective COX-2 inhibitor, on early anastomotic healing was investigated. METHODS: Celecoxib, in doses of 15, 50 or 200 mg per kg per day, was given daily from the day before operation onwards to male Wistar rats that received both ileal and colonic anastomoses. Anastomotic strength was assessed by measuring the breaking strength and bursting pressure on the third day after operation. A second group received a dose of 50 mg per kg per day and a colonic anastomosis only, and healing was assessed on the third and fifth day after surgery. RESULTS: Expression of COX-2 protein was upregulated in the anastomotic area. Administration of celecoxib, at all doses tested, resulted in a significantly higher ileal dehiscence rate than in control rats (P = 0.002). In contrast, colonic anastomoses healed normally within the same animals. The latter was confirmed in rats with colonic anastomoses only. CONCLUSION: In this model, administration of the COX-2 inhibitor celecoxib affected ileal but not colonic anastomotic healing in the early postoperative period.
Asunto(s)
Colon/cirugía , Inhibidores de la Ciclooxigenasa/uso terapéutico , Íleon/cirugía , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Celecoxib , Colon/metabolismo , Hidroxiprolina/metabolismo , Íleon/metabolismo , Masculino , Metaloproteinasas de la Matriz/metabolismo , Periodo Posoperatorio , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
BACKGROUND: Little is known about the impact of repeated laparotomies on intestinal anastomotic healing. While experimental data are completely lacking, the sparse data available from clinical studies report high anastomotic failure rates, suggesting a negative effect in this respect. Since the unequivocal determination of such an effect may have important consequences for choosing the optimal treatment strategy for patients suffering from intra-abdominal infection, an experimental study has been performed in an established rodent model. METHODS: Intestinal anastomoses were constructed in healthy Wistar rats (ileal and colonic anastomoses) or 24 h after peritonitis was induced by caecal ligation and puncture (colonic anastomosis only). Rats were then scheduled to undergo no, one (after 24 h) or two relaparotomies (after 24 and 48 h). Anastomotic strength was assessed 3 and 5 days after anastomotic construction. On the third post-operative day anastomotic hydroxyproline levels, matrix metalloproteinase activity and myeloperoxidase activity were measured. RESULTS: No negative impact of repeated laparotomies was measured on any of the parameters measured. Under non-infectious conditions even an improvement in breaking strength (+48%, p=0.017) but not bursting pressure was found after two relaparotomies, but only in the ileum on the third post-operative day. CONCLUSIONS: In this experimental setting, early anastomotic healing is not adversely affected by repeated laparotomies.
Asunto(s)
Colon/cirugía , Íleon/cirugía , Laparotomía , Cicatrización de Heridas/fisiología , Anastomosis Quirúrgica/métodos , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Hidroxiprolina/metabolismo , Masculino , Metaloproteinasas de la Matriz/metabolismo , Peroxidasa/metabolismo , Ratas , Ratas Wistar , ReoperaciónRESUMEN
The aim of this study was to assess the interventions by general practitioners on cardiovascular risk factors among persons without a history of cardiovascular disease attending for a cardiovascular check-up. All inhabitants of three Belgian towns aged between 45 and 64 years were invited for a cardiovascular check-up and blood test. Of all the attending persons without a history of cardiovascular disease (n = 898), 51% received at least one prescription, diet or health advice: 28% for hyperlipidaemia, 23% for physical activity, 22% for caloric intake, 9% for blood sugar, 5% for blood pressure and 4% for smoking. Interventions on lipoproteins, blood sugar and smoking habits were significantly more often proposed to persons with a medium or high cardiovascular risk compared to those at low cardiovascular risk. For persons at low cardiovascular risk, therapeutic lifestyle changes are often not advised, and isolated risk factors often remain untreated.
Asunto(s)
Enfermedad Coronaria/prevención & control , Glucemia/metabolismo , Índice de Masa Corporal , Peso Corporal , Enfermedad Coronaria/sangre , Estudios Transversales , Medicina Familiar y Comunitaria , Femenino , Humanos , Hipertensión/prevención & control , Lípidos/sangre , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Factores de Riesgo , Prevención del Hábito de FumarRESUMEN
BACKGROUND: A relationship between post-surgical adhesion formation and peritoneal tumour implantation has been proposed. Hyaluronan (HA)-based agents reduce adhesion formation, but the effect on peritoneal tumour is not established. This study investigated the influence of a HA-containing agent on intraperitoneal tumour in an experimental model. METHODS: 66 Balb/c mice underwent laparotomy and damage was inflicted to the parietal peritoneum. The animals were randomized into five groups. Groups 1 and 2 received HA-carboxymethylcellulose bioresorbable membrane and no treatment, respectively. Mice in groups 3-5 were injected intraperitoneally with 10(5) colon 26-B cells after the laparotomy. Treatment consisted of HA membrane, no HA agent and placement of HA membrane on the non-traumatized peritoneal wall, respectively. Animals were killed after 14 days; adhesions were scored in groups 1 and 2, and the tumour mass in groups 3-5. 45 Wag/Rij rats underwent the same procedures and treatment as mice in groups 3-5. In rats, 10(6) CC-531 cells were injected. Rats were killed after 3 weeks and the tumour mass was scored. RESULTS: HA membrane resulted in a significant reduction of adhesions, but had no major effect on the intraperitoneal tumour mass in mice and rats. CONCLUSION: HA-carboxymethylcellulose bioresorbable membrane has no major effect on intraperitoneal tumour implantation and growth in an experimental model.
Asunto(s)
Carboximetilcelulosa de Sodio/farmacología , División Celular/efectos de los fármacos , Neoplasias del Colon/fisiopatología , Ácido Hialurónico/farmacología , Adherencias Tisulares/prevención & control , Animales , Línea Celular Tumoral , Laparotomía/efectos adversos , Membranas Artificiales , Ratones , Modelos Animales , Cavidad Peritoneal , Peritoneo/lesiones , Peritoneo/fisiopatología , Adherencias Tisulares/etiologíaRESUMEN
BACKGROUND: Clinical studies report conflicting results on the safety of primary intestinal anastomoses in the presence of peritonitis, and comprehensive experimental data are lacking. The present study investigated whether the strength of experimental colonic anastomoses is affected if surgery is performed in the presence of pre-existing bacterial peritonitis. METHODS: Colonic anastomoses were constructed in Wistar rats 24 h after caecal ligation and puncture or a sham procedure. Anastomotic strength was assessed by measuring breaking strength and bursting pressure during the first 5 days after operation. Anastomotic hydroxyproline levels were measured and matrix metalloproteinase (MMP) activity was analysed by quantitative gelatin zymography. RESULTS: Anastomotic strength was lowered in the presence of bacterial peritonitis but in a minor and transient way. The breaking strength was lower only immediately after construction of the anastomosis (- 15 per cent, P = 0.011) and the bursting pressure only on the third postoperative day (- 33 per cent, P = 0.038); no anastomotic dehiscence was observed. At 3 days after operation increased levels of MMP activity were observed but anastomotic hydroxyproline content was not affected by bacterial peritonitis. CONCLUSION: The influence of bacterial peritonitis on the development of anastomotic strength is limited. This experimental finding lends support to recent clinical studies that have demonstrated the feasibility of constructing a primary anastomosis under these conditions.
Asunto(s)
Infecciones Bacterianas/enzimología , Metaloproteinasas de la Matriz/metabolismo , Peritonitis/enzimología , Anastomosis Quirúrgica/normas , Animales , Peso Corporal , Masculino , Periodo Posoperatorio , Ratas , Ratas WistarRESUMEN
BACKGROUND AND AIMS: The strength of intestinal anastomoses is relatively low in the first days after operation, possibly as a result of localized degradation of the supporting matrix by enzymes from the matrix metalloproteinase (MMP) family. This study examined whether BB-94, a broad spectrum inhibitor of MMP activity, could enhance anastomotic strength. MATERIALS AND METHODS: Male Wistar rats received anastomoses in both ileum and colon. From the day before operation onwards, animals were treated daily with BB-94 intraperitoneally at a dose of 30 mg/kg or with saline only. Rats were killed 1, 3, or 7 days after operation, and anastomotic bursting pressure and breaking strength were measured. On day 3 anastomotic hydroxyproline levels were measured, and MMP (gelatinase) activity was analyzed by gelatin zymography. RESULTS: BB-94 strongly enhanced wound strength, but only on day 3, when it was at its lowest. Daily administration increased median colonic and ileal breaking strength by 27% and 108%, respectively; colonic and ileal bursting pressure were increased by 54% and 58%, respectively. MMP activities were significantly lowered in anastomotic extracts from the rats treated with BB-94. CONCLUSION: Administration of BB-94 enhances anastomotic strength. Specific inhibition of MMP activity should be investigated further as a means to preserve anastomotic integrity.
Asunto(s)
Colon/fisiología , Colon/cirugía , Íleon/fisiología , Íleon/cirugía , Inhibidores de la Metaloproteinasa de la Matriz , Metaloproteinasas de la Matriz/efectos de los fármacos , Fenilalanina/análogos & derivados , Fenilalanina/farmacología , Inhibidores de Proteasas/farmacología , Tiofenos/farmacología , Anastomosis Quirúrgica , Animales , Colon/efectos de los fármacos , Hidroxiprolina/efectos de los fármacos , Íleon/efectos de los fármacos , Masculino , Modelos Animales , Periodo Posoperatorio , Ratas , Ratas Wistar , Factores de Tiempo , Resultado del TratamientoRESUMEN
A new iterative maximum-likelihood reconstruction algorithm for X-ray computed tomography is presented. The algorithm prevents beam hardening artifacts by incorporating a polychromatic acquisition model. The continuous spectrum of the X-ray tube is modeled as a number of discrete energies. The energy dependence of the attenuation is taken into account by decomposing the linear attenuation coefficient into a photoelectric component and a Compton scatter component. The relative weight of these components is constrained based on prior material assumptions. Excellent results are obtained for simulations and for phantom measurements. Beam-hardening artifacts are effectively eliminated. The relation with existing algorithms is discussed. The results confirm that improving the acquisition model assumed by the reconstruction algorithm results in reduced artifacts. Preliminary results indicate that metal artifact reduction is a very promising application for this new algorithm.
Asunto(s)
Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Modelos Teóricos , Fantasmas de Imagen , Tomografía Computarizada por Rayos X/instrumentaciónRESUMEN
BACKGROUND: Hyaluronic acid (HA) agents reduce postsurgical adhesion formation. The effect of their perioperative administration on early anastomotic healing is unknown. This study investigated the influence of two HA-containing agents on the development of strength in colonic anastomosis during the first postoperative week, both in normal rats and in rats with bacterial peritonitis. METHODS: In 90 male Wistar rats a 1-cm segment was resected from the descending colon and an end-to-end anastomosis was constructed. In 108 rats a bacterial peritonitis was induced using caecal ligation and puncture (CLP). Some 24 h after CLP the abdomen was reopened, the caecum was taken out and, after resection of a 1-cm segment, an anastomosis was made. Animals in both groups were randomized to receive either an HA-carboxymethylcellulose (CMC) bioresorbable membrane, 0.4 per cent HA solution or no treatment. One-third of each group was killed at day 1, 3 and 7 after operation. Cultures were taken from the abdominal cavity for microbiological analysis in half of the animals. Subsequently, both bursting pressure and breaking strength were determined as parameters for anastomotic strength. RESULTS: No differences in anastomotic bursting pressure or breaking strength were found between the experimental groups and their controls. In addition, there was no significant difference in the number of bacteria cultured from the abdominal cavity between rats treated with HA and controls. CONCLUSION: Neither HA-CMC bioresorbable membrane nor 0.4 per cent HA solution interferes with the development of early anastomotic strength in the colon, and can therefore be safely used to prevent intra-abdominal adhesion formation after performing bowel anastomosis.
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Adyuvantes Inmunológicos/uso terapéutico , Infecciones Bacterianas/complicaciones , Ácido Hialurónico/uso terapéutico , Peritonitis/complicaciones , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Infecciones Bacterianas/fisiopatología , Masculino , Peritonitis/fisiopatología , Presión , Ratas , Ratas Wistar , Dehiscencia de la Herida Operatoria/fisiopatología , Dehiscencia de la Herida Operatoria/prevención & controlRESUMEN
Integrated backscatter (IB) from a myocardial region, calculated from radiofrequency echocardiographic data, has been proposed as a useful parameter for investigating changes in myocardial tissue induced by ischemia. In 10 closed-chest dogs, 5 minutes of myocardial ischemia was induced by either a proximal occlusion of the circumflex coronary artery (CX) (5 dogs), resulting in extensive ischemia in the posterior wall, or by occluding the distal CX vessel (5 dogs) to produce a small localized ischemic zone in the posterior wall. High-resolution digital radiofrequency data from the whole left ventricular myocardium, in the imaging plane during one complete heart cycle, were acquired with a whole-image real-time acquisition approach. Regions in the septum and posterior wall (both ischemic tissue and, in the case of distal occlusions, tissue surrounding the ischemic zone) were chosen for analysis, and IB and cyclic variation (CV) of IB were calculated. Post occlusion, an increase in mean IB values was found in the ischemic segment. However, an increase in CV was also observed in the peri-ischemic zone for the distal CX occlusion and in the septum after proximal CX occlusion. These findings show that changes in CV are not restricted to the ischemic zone but may also occur in distal myocardium. This may be explained by changes in the regional contractile state and loading conditions of the "normal" myocardium, which are altered in response to the distal ischemia.
Asunto(s)
Isquemia Miocárdica/diagnóstico por imagen , Animales , Perros , Procesamiento de Imagen Asistido por Computador , Ultrasonido , UltrasonografíaRESUMEN
We investigated the effect of interleukin 10 on the development of zymosan-induced multiple organ dysfunction syndrome (MODS) and on plasma concentrations and production capacity of tumour necrosis factor (TNF)-alpha by peritoneal cells. Groups of C57BL/6 mice received a single intraperitoneal injection with zymosan, a cell wall component of Saccharomyces cerevisiae, at day 0. Daily doses of human recombinant interleukin 10 (IL-10: 10 or 50 microg/kg) were given intraperitoneally either starting directly before administration of zymosan (day 0), or 5 or 8 days after administration of zymosan. The animals were monitored for survival, condition, body weight and temperature. On day 12 all surviving animals were killed to obtain plasma, organs and peritoneal cells. Plasma concentrations of TNF-alpha and lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells were measured; organ weights were registered as an indicator for organ damage. IL-10 improves survival and clinical condition and also reduces organ damage, but only at the highest dose used and only when started simultaneously with the administration of zymosan. Circulating TNF-alpha concentrations 12 days after zymosan are not affected by any of the IL-10 schedules used. However, lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells is increased, in a dose- and time-dependent fashion. The anti-inflammatory cytokine IL-10 is able to attenuate the development of MODS in this model, but only when given simultaneously with zymosan, and in high dosages.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Interleucina-10/uso terapéutico , Macrófagos Peritoneales/efectos de los fármacos , Insuficiencia Multiorgánica/prevención & control , Zimosan/toxicidad , Animales , Antiinflamatorios no Esteroideos/farmacología , Peso Corporal/efectos de los fármacos , Citocinas/biosíntesis , Citocinas/genética , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Regulación de la Expresión Génica/efectos de los fármacos , Hemorragia/inducido químicamente , Humanos , Hipotermia/inducido químicamente , Interleucina-10/farmacología , Lipopolisacáridos/farmacología , Hígado/patología , Pulmón/patología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos C57BL , Insuficiencia Multiorgánica/inducido químicamente , Tamaño de los Órganos/efectos de los fármacos , Proteínas Recombinantes/farmacología , Bazo/patología , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Early post-operative local or systemic administration of 5-fluorouracil (5-FU) is under investigation as a means to improve outcome after resection of intestinal malignancies. It is therefore quite important to delineate accurately its potentially negative effects on anastomotic repair. Five groups (n = 24) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving daily 5-FU, starting immediately after operation or after 1, 2 or 3 days. Within each group, the drug (or saline) was delivered either intraperitoneally (n = 12) or intravenously (n = 12). Animals were killed 7 days after operation and healing was assessed by measurement of anastomotic bursting pressure, breaking strength and hydroxyproline content. In all cases, 5-FU treatment from the day of operation or from day 1 significantly (P<0.025) and severely suppressed wound strength; concomitantly, the anastomotic hydroxyproline content was reduced. Depending on the location of the anastomosis and the route of 5-FU administration, even a period of 3 days between operation and first dosage seemed insufficient to prevent weakening of the anastomosis. The effects of intravenous administration, though qualitatively similar, were quantitatively less dramatic than those observed after intraperitoneal delivery. Post-operative treatment with 5-FU, if started within the first 3 days after operation, is detrimental to anastomotic strength and may compromise anastomotic integrity.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Fluorouracilo/efectos adversos , Neoplasias Intestinales/tratamiento farmacológico , Neoplasias Intestinales/cirugía , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Antimetabolitos Antineoplásicos/uso terapéutico , Colon/cirugía , Fluorouracilo/uso terapéutico , Íleon/cirugía , Infusiones Intravenosas , Infusiones Parenterales , Masculino , Complicaciones Posoperatorias , RatasRESUMEN
Intraoperative irradiation appears to be a valuable addition to the modalities available to treat patients with large bowel cancer. However, its potential effect on healing of anastomoses has not been investigated extensively. For this purpose, male Wistar rats underwent colonic resection. Subsequently, 1 cm of each bowel end was irradiated with doses of 10, 15, 20 or 25 Gy and intestinal continuity was restored. After 3 or 7 days, animals were killed and the anastomoses were analyzed for bursting pressure (intraluminal force), breaking strength (longitudinal force) and hydroxyproline content. Intraoperative irradiation led to a massive (40-70%) and significant (P < 0.025) reduction in bursting pressure 3 days after operation compared to the control group for every dose used. After 7 days, the bursting site was outside the area of the anastomosis in all groups. The breaking strength at day 3 was also reduced, even after 10 Gy. At day 7, when tearing still occurred in the wound area, the breaking strength was still significantly lower in the 15- and 25-Gy groups than in the control group. The hydroxyproline content of the anastomoses was significantly reduced only after irradiation with the higher doses. Thus intraoperative irradiation constitutes a threat to early strength of anastomoses in the rat colon, and even at moderate doses it may threaten the integrity of the anastomosis.
Asunto(s)
Colon/efectos de la radiación , Neoplasias del Colon/terapia , Dosificación Radioterapéutica , Anastomosis Quirúrgica/normas , Animales , Colon/cirugía , Neoplasias del Colon/radioterapia , Neoplasias del Colon/cirugía , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Periodo Intraoperatorio , Masculino , Ratas , Ratas WistarRESUMEN
Experimental studies indicate that anastomotic healing in the intestine is compromised by the immediate postoperative administration of 5-fluorouracil and levamisole. Since fibroblast functions are crucial to healing, we investigated the effects of (combinations of) both drugs on proliferation and collagen synthesis of rat skin fibroblasts in vitro. Proliferation was measured in actively dividing cells by cellular [3H]thymidine uptake and collagen synthesis in non-dividing cells by [3H]proline incorporation into collagenase-digestible protein. 5-Fluorouracil strongly and significantly (P < 0.05) reduced DNA synthesis and collagen synthesis at concentrations of 1 microM or more. The latter effect was not specific for collagen since total protein production was affected similarly. Both effects depended on the duration of exposure to the drugs. Levamisole also inhibited fibroblast proliferation dose-dependently, but less effectively than 5-fluorouracil: 50% inhibition was observed at approximately 0.1 mM. Collagen synthesis was unaffected by levamisole. If levamisole was added together with a low (0.1 microM) concentration of 5-fluorouracil, which in itself did not decrease thymidine incorporation, levamisole's antiproliferative effects became apparent at concentrations as low as 1 microM. A similar effect, but at a much higher concentration (1 mM) was noted on fibroblast collagen synthesis. These results indicate that levamisole potentiates 5-fluorouracil effects in fibroblast cultures and that direct effects of these drugs, alone or in combination, on fibroblast proliferation and collagen synthesis may be responsible for their negative influence on wound repair.
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Adyuvantes Inmunológicos/farmacología , Antineoplásicos/farmacología , Colágeno/efectos de los fármacos , Fluorouracilo/farmacología , Levamisol/farmacología , Anastomosis Quirúrgica , Animales , División Celular , Colágeno/biosíntesis , Combinación de Medicamentos , Sinergismo Farmacológico , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Masculino , Ratas , Ratas Wistar , Cicatrización de HeridasRESUMEN
Iterative reconstruction algorithms for helical CT are presented. The algorithms are derived from two-dimensional reconstruction algorithms, by adapting the projector/backprojector to the helical orbit of the source, and by constraining the axial frequencies with a Gaussian sieve. Simulations have been carried out and the performance of the iterative algorithms is compared to that of filtered backprojection of synthetic (interpolated) two-dimensional sinograms. The iterative algorithms produce superior bias-noise curves. Axial resolution is superior, but disturbing edge-artefacts are introduced.
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Procesamiento de Imagen Asistido por Computador/métodos , Fantasmas de Imagen , Tomografía Computarizada por Rayos X , Algoritmos , Artefactos , Calibración , Simulación por Computador , Humanos , Funciones de VerosimilitudRESUMEN
Hyperthermia is a promising method for increasing the efficacy of radiation therapy of colorectal cancer. To study the histological aspects of healing of an anastomosis in the colon, after combined preoperative (sham) irradiation and (sham) hyperthermia treatment, 48 male Wistar rats were divided randomly into four groups. In each animal, a segment of the colon was treated successively by (sham) irradiation (single dose of 25 Gy X rays) and/or (sham) hyperthermia (44 degrees C, 30 min). After 5 days, a resection of the colon was performed by construction of an anastomosis: The distal limb consisted of (sham-) irradiated and/or (sham-) hyperthermia-treated bowel. Rats were killed 3 or 7 days after the surgical procedure. Evaluation of healing of the anastomosis was made by: (1) histological analysis of sections stained with hematoxylin and eosin, (2) semiquantitative measurement of collagen in the area of the anastomosis and (3) semiquantitative analysis of the number of macrophages by immunocytochemistry. Healing of the anastomoses in animals receiving irradiation or hyperthermia alone and in control animals was relatively uneventful. There were no differences between groups in formation of collagen or infiltration by macrophages in the area of the anastomosis. Animals treated with both radiation and hyperthermia showed marked necrosis, infiltration by polymorphonuclear leukocytes and rupture of the anastomosis. It is concluded that preoperative irradiation with a single dose of 25 Gy in combination with local hyperthermia at 44 degrees C for 30 min leads to disturbed repair of anastomoses.
Asunto(s)
Colon/cirugía , Cicatrización de Heridas/efectos de la radiación , Anastomosis Quirúrgica , Animales , Colágeno/metabolismo , Colon/efectos de la radiación , Hipertermia Inducida , Inflamación/patología , Macrófagos/fisiología , Masculino , Necrosis , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
There exists a growing interest in intra-operative radiation therapy as a treatment modality for large bowel cancer. In a previous experimental study we showed that high-dose intra-operative irradiation delays the healing of colonic anastomoses. However, the contribution of proteases is unknown. In the present study, the gelatinolytic and collagenolytic activity in the healing anastomoses is investigated. After a resection of a 1-cm length of colon (uninjured colon), the rats were irradiated with a single dose of 25 Gy, either to the proximal limb, referred to as the proximal group, or to both proximal and distal limbs of the bowel, referred to as the combined group, before anastomotic construction. Both groups were compared to a control group with anastomoses which were sham-irradiated. The animals were killed 1, 3 or 7 days after operation. The gelatinolytic activity in uninjured and anastomotic tissue was quantified by gelatin zymography and the collagenolytic activity by an assay using a fibrillar rat collagen substrate. Compared with resected uninjured colon, most of the gelatinolytic activities were markedly increased in anastomotic tissue of all groups during the first postoperative week, and new additional activities were detected. The additional metalloproteinases (the 95-kDa family) of both irradiated groups were significantly elevated compared to the anastomoses of the sham-irradiated control group at 7 days after operation. In anastomotic tissue of all groups, the collagenolytic activity of the tissue was also significantly increased at 1 and 3 days after construction with respect to the resected, uninjured colon. After 7 days this effect had disappeared for the sham-irradiated anastomoses, but the activity in the anastomoses in both the proximal and combined groups remained significantly elevated. The findings provide evidence that intra-operative irradiation prolongs the presence of elevated gelatinolytic and collagenolytic activities in colon anastomoses. It may contribute to a reduced or delayed accumulation of collagen and other matrix proteins that supply anastomotic strength.
Asunto(s)
Colagenasas/metabolismo , Colon/efectos de la radiación , Cicatrización de Heridas/efectos de la radiación , Anastomosis Quirúrgica , Animales , Colágeno/metabolismo , Masculino , Peso Molecular , Ratas , Ratas WistarRESUMEN
BACKGROUND AND PURPOSE: Preoperative irradiation with direct postoperative chemotherapy could benefit patients undergoing surgery for colorectal cancer. This study was designed to examine, in an experimental model, if such treatment is feasible without detrimental effects on early anastomotic healing. MATERIAL AND METHODS: A colonic segment was irradiated (25 Gy) in 3 groups (n = 10 each) of male Wistar rats. After 5 days, a colonic resection was performed with anastomotic construction; only the distal limb consisted of irradiated bowel. Postoperatively, animals received daily intraperitoneal 5-fluorouracil (5-FU, group I/CH: 17.5 mg/kg; group I/CL: 12.5 mg/kg) or saline (group I). Three additional groups were treated similarly, but with sham-irradiation: CH, CL and C, respectively. All rats were killed 7 days postoperatively. Parameters measured were: weight, serum albumin and protein, and anastomotic bursting pressure, breaking strength and hydroxyproline content. RESULTS: Body weight was diminished significantly in rats receiving chemotherapy. Serum albumin and protein was significantly lower in irradiated groups. At sacrifice, 40% of I/CH rats had functional rectal stenosis. The average bursting pressure (P = 0.0005) and the average breaking strength (P = 0.012) were only reduced significantly in the CH group. The anastomotic hydroxyproline content was significantly higher in the I/CH and I/CL groups vs. the control group. CONCLUSION: High-dose direct postoperative 5-FU leads to reduced anastomotic strength. Although the combination of preoperative irradiation (25 Gy) and direct postoperative high-dose 5-FU does not reduce early anastomotic strength, some stenosis may occur. The combination of preoperative irradiation and low-dose 5-FU has no such effect.