RESUMEN
BACKGROUND: It has been well established that open abdominal surgery results in systemic immunosuppression postoperatively; in contrast, laparoscopic surgery is associated with significantly better preserved systemic immune function. However, when intraperitoneal (local) immune function is considered, laparoscopic procedures done under a CO2 pneumoperitoneum (pneumo) have been shown to result in greater immunosuppression compared to that of open surgery. Few studies have simultaneously assessed systemic and local immune function. The purpose of this study was to assess peripheral blood mononuclear cell (PBMC) and peritoneal macrophage tumor necrosis factor-alpha (TNF-alpha) levels, H2O2 production, and MHC class II antigen expression after open and laparoscopically assisted cecectomy in a rat model. METHODS: A total of 75 Sprague Dawley rats were used for three separate experiments. For each study, rats were randomly divided into three groups: anesthesia alone (AC), laparoscopic-assisted cecectomy (LC), and open cecectomy via full laparotomy (OP). A CO2 pneumo was used for laparoscopic operations. On postoperative day 1 the animals were sacrificed, macrophages were harvested via intraperitoneal lavage, and PBMCs were isolated from whole blood obtained by cardiac puncture. In experiment 1, macrophages and PBMC from each animal were stimulated with lipopolysaccharide, after which TNF-alpha levels of the supernatant were determined. In experiment 2, after stimulation with PMA, H2O2 release was assessed by measuring fluorescence. In experiment 3, via flow cytometry, the number of cells with surface MHC class II proteins were determined. Data from the three groups in each experiment were compared using analysis of variance Tukey-Kramer tests. RESULTS: Macrophages and PBMC from rats in the OP group released significantly more TNF-alpha than cells from rats in the LC ( p < 0.05) or AC ( p < 0.05) groups. Macrophages from rats in the OP group released significantly less H2O2 than cells from the AC ( p < 0.01) and LC ( p < 0.05) groups. There was no difference between the AC and LC results. No significant differences in PBMC H2O2 release were noted among any of the groups. OP group macrophages expressed significantly less MHC class II antigen than did AC group macrophages ( p < 0.05). No differences were noted among the LC results and either the OP or AC group's outcomes. No differences were noted in PBMC MHC class II expression among any of the groups. CONCLUSIONS: In all instances, the LC group's macrophage results were similar to the AC group's results. OC group macrophages produced significantly more TNF-alpha and less H2O2 than both the AC and LC groups. MHC class II protein expression was less for the OC group than for the AC group. OC group PBMCs produced more TNF-alpha. No differences in PBMC H2O2 release or MHC class II expression were noted. Laparoscopic methods better preserves the baseline values of the parameters studied.
Asunto(s)
Ciego/cirugía , Laparoscopía , Laparotomía , Macrófagos Peritoneales/fisiología , Monocitos/fisiología , Animales , Dióxido de Carbono , Antígenos de Histocompatibilidad Clase II/biosíntesis , Peróxido de Hidrógeno/metabolismo , Terapia de Inmunosupresión , Lipopolisacáridos/farmacología , Activación de Macrófagos/efectos de los fármacos , Masculino , Neumoperitoneo Artificial , Periodo Posoperatorio , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Our laboratory has previously shown that tumors are established more easily and grow larger after laparotomy than after laparoscopy. To characterize these differences in tumor growth further, the tumor cell death rates and tumor proliferation rates were compared in vivo after full sham laparotomy versus carbon dioxide (CO2) insufflation. METHODS: Female Balb/C mice (n = 36) were inoculated intradermally in the dorsal skin with 106 C-26 colon adenocarcinoma cells in 0.1 ml of culture media no more than 1 h before interventions. The mice then were randomized to one of three groups: anesthesia control, CO2 insufflation, or sham laparotomy. The anesthesia control group underwent no procedure. The insufflation group underwent CO2 pneumoperitoneum (4-6 mmHg) for 20 min via a 20-gauge angiocatheter. The laparotomy group underwent a midline incision from xiphoid to pubis, which was closed after 20 min. Tumors were excised from half the mice in each group on postoperative day 7, and from the remaining mice on postoperative day 14. Sections of tumors were made then stained separately for free 3? hydroxyl ends of genomic deoxyribonucleic acid (DNA) using fluorescein-deoxyunidine triphosphate (dUTP), and immunohistochemically for proliferating cell nuclear antigen (PCNA). Apoptosis was measured by quantitating DNA strand breaks in individual cells using fluorescence microscopy. Fluorescein-positive cells in five random high-power fields (x200) were counted in a blinded fashion. The proliferative index of each tumor was determined by averaging PCNA positive cells in five high-power fields (x450) counted in a blinded fashion with the aid of an optical grid. RESULTS: On postoperative day 7, there was no significant difference in the proliferative index or apoptotic rates among the three groups. On postoperative day 14, the proliferative index in the laparotomy group was significantly higher than in either the insufflation or control group (p < 0.001). The proliferative index in the insufflation group also was significantly higher than in the control group (p < 0.05). Inverse differences in apoptotic rates were found. The apoptotic rate in the laparotomy group was significantly lower than in either the insufflation (p < 0.05) or control group (p < 0.001). The apoptotic rate in the insufflation group was significantly lower than in the control group (p < 0.001). CONCLUSIONS: We have demonstrated that there is a significantly higher rate of tumor cell proliferation and a significantly lower rate of tumor cell death with the C-26 colon adenocarcinoma tumor line after laparotomy than after insufflation or anesthesia alone on post-operative day 14. The mechanisms of these phenomena are unclear. It appears that certain factors postoperatively stimulate tumors to proliferate at a higher rate, causing tumor cells to die at a lower rate in the laparotomy group than in the insufflation group.
Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/cirugía , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Insuflación/métodos , Laparotomía/métodos , Adenocarcinoma/química , Animales , Dióxido de Carbono/uso terapéutico , Muerte Celular , División Celular , Neoplasias del Colon/química , Femenino , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias/métodos , Periodo Posoperatorio , Antígeno Nuclear de Célula en Proliferación/análisis , Células Tumorales CultivadasRESUMEN
BACKGROUND: Although adenomatous polyps have been established clearly as precursor lesions for most cases of colorectal cancer, the role, if any, of hyperplastic polyps remains uncertain. The aim of the current study was to determine whether a patient with an index finding of hyperplastic polyp on colonoscopy is at increased risk for adenomatous polyps. METHODS: We conducted a retrospective cohort study using the records of a single surgeon's colonoscopic experience over a 20-year period (June 1973 to December 1994). Patients found to have hyperplastic lesions on index colonoscopy were compared with those who had "clean" index colonoscopies. The two groups were compared for the subsequent diagnosis of adenomatous polyps on follow-up colonoscopies. Those with cancer or adenomas at index colonoscopy or in their history were excluded. We used Cox proportional hazard modeling with subsequent adenoma or cancer diagnosis at follow-up colonoscopy as the outcome, controlling for age and gender. RESULTS: We identified 42 patients for whom hyperplastic polyps were the only colorectal neoplasms found on the index examination, in contrast to 362 control patients who had a "clean" index examination. In this cohort study, patients found to have only hyperplastic polyps on initial examination had a rate of subsequent adenoma diagnoses (42%) twice that of patients with a clean initial colonoscopy (21%). Mean follow-up time was 4.3 years. The relative rate ratio was 2.0 (95% confidence interval, 1.2-3.4). CONCLUSIONS: This study suggests that patients found to have hyperplastic polyps on initial colonoscopic examination may have twice the risk of adenomas on follow-up colonoscopy, as compared with those who have clean initial examinations. If this finding is borne out in larger prospective studies, surveillance strategies may need to be modified accordingly.
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Adenoma/epidemiología , Pólipos del Colon/epidemiología , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/epidemiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiología , Adenoma/diagnóstico , Adenoma/patología , Pólipos Adenomatosos/diagnóstico , Pólipos Adenomatosos/epidemiología , Estudios de Cohortes , Pólipos del Colon/diagnóstico , Pólipos del Colon/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Intervalos de Confianza , Estudios de Seguimiento , Humanos , Hiperplasia , Incidencia , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: Our laboratory has demonstrated that tumors grow larger and are more easily established following laparotomy than after carbon dioxide (CO2) pneumoperitoneum or anesthesia alone. We have also shown that tumor cells incubated with serum from laparotomized mice proliferated significantly faster in vitro than those incubated with plasma from mice that underwent laparoscopy or anesthesia alone. We hypothesized that differing levels of a plasma-soluble growth factor(s) postoperatively causes tumors to proliferate faster after laparotomy. This study's purpose was to isolate and characterize the plasma growth factor(s) responsible for the increased growth of systemic tumors after laparotomy. METHODS: Female Balb/C mice (n = 100) were randomized to two groups: anesthesia control (AC) or midline sham laparotomy (4 cm) (Open). Plasma was collected on Postoperative day 4. For the tumor proliferation assay, C-26 colon cancer cells were incubated in media with either 10% AC or Open "raw" plasma (not passed through column), or AC or Open plasma that had been passed through the column. For elution of heparin-binding proteins, plasma from each group was passed through a heparin-sepharose column. Elution of bound proteins was accomplished with a 0.1-2 M NaCl gradient. Each fraction was examined for protein content. For the anti-platelet-derived growth factor (PDGF) neutralizing antibody study, C-26 cells were incubated with one of four plasma preparations: AC or Open plasma alone, or AC or Open plasma incubated with anti-PDGF antibody. For both studies, tumor proliferation was determined after 2 days with an MTS/PMS assay. Results from each group were compared and differences determined using analysis of variance (ANOVA) and Tukey-Kramer tests. RESULTS: On heparin chromatography, a single elution peak consistent with PDGF was present in both AC and Open plasma and was 1.5 times greater in the Open plasma. The first tumor proliferation assay showed that tumor cells incubated with Open plasma proliferated 2.5 times faster than those with AC plasma (p < 0.0001). Passage of AC plasma through the column did not alter its mitogenic activity, but Open plasma thus treated demonstrated significantly decreased mitogenic activity. The second tumor proliferation assay showed that anti-PDGF antibody had no effect on the mitogenic activity of the AC plasma but decreased the mitogenic activity of the Open plasma to the AC plasma level. CONCLUSIONS: Laparotomy is associated with higher levels of a heparin-binding plasma factor, consistent with PDGF. The enhanced mitogenic activity of the OP plasma was neutralized with anti-PDGF antibody. Increased plasma levels of PDGF after laparotomy may be responsible for accelerated tumor growth following laparotomy in mice.
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Neoplasias del Colon/sangre , Laparotomía/métodos , Factor de Crecimiento Derivado de Plaquetas/análisis , Adenocarcinoma/sangre , Adenocarcinoma/metabolismo , Animales , División Celular , Neoplasias del Colon/metabolismo , Femenino , Sustancias de Crecimiento/sangre , Laparotomía/efectos adversos , Ratones , Ratones Endogámicos BALB C , Células Tumorales Cultivadas/metabolismoRESUMEN
Controversy remains regarding the appropriateness of laparoscopic methods for the curative resection of colonic neoplasms. Long-term results after minimally invasive resection must be shown to be equivalent or better than those after open resection in order to justify the new technique in the setting of cancer. This article discusses adequacy of resection and short-term results, long-term outcome data, port and abdominal wound tumors, oncologic and immunologic basic science data, and the role of laparoscopy in the treatment of rectal cancers.
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Neoplasias Colorrectales/cirugía , Laparoscopía/métodos , Anastomosis Quirúrgica , Animales , Colonoscopía/efectos adversos , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Ensayos Clínicos Controlados como Asunto , Femenino , Humanos , Laparoscopía/efectos adversos , Masculino , Complicaciones Posoperatorias , Pronóstico , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The etiology of port site tumor recurrences following laparoscopic surgery for cancer remains unknown. A recent study from our laboratory using a murine splenic tumor model suggests that it is poor surgical technique (i.e., crushing of the tumor) rather than the CO2 pneumoperitoneum that is responsible for these tumors. However, in that experiment, no intraabdominal procedure was carried out. We subsequently performed a preliminary study in which we compared the rate of port site tumor recurrences after laparoscopic-assisted splenectomy (LAS) vs open splenectomy (OS) using the murine splenic tumor model. In this study, we found significantly more port and incisional tumors after laparoscopic splenectomy. The reasons for this finding are unclear. Further analysis of the data showed that the incidence of port tumors in the LAS group decreased dramatically from the first to the second trial, suggesting that the experience of the surgeon may play a role. The purpose of the current study was to carry out further trials to determine if the lower rate of port tumor recurrence in the laparoscopic group will persist with increased surgical experience. METHODS: Splenic tumors were established in female Balb/C mice (n = 128) via a subcapsular injection of a 0.1-cc suspension containing 10(5) C-26 colon adenocarcinoma cells via a left flank incision at the initial procedure. Seven days later, the animals with isolated splenic tumors (95%) were randomized to one of two groups-open splenectomy (OS) or laparoscopic-assisted splenectomy (LAS). Three ports were placed in similar locations in all animals. The OS mice underwent an open splenectomy via a subcostal incision and anesthesia for 20 min. The LAS mice underwent laparoscopic mobilization of the spleen using a three-port technique, followed by an extracorporeal splenectomy via a subcostal incision. Seven days after splenectomy, the mice were killed and inspected for abdominal wall tumor implants. The experiment was carried out in four separate trials. RESULTS: When the results of the four trials were combined, there was no significant difference in the incidence of animals with at least one port tumor recurrence between the OS vs the LAS group (25% vs 35.2%; p = 0.30, power = 0.91). However, the overall incidence of port site tumors (number of ports with tumors/total number of ports for each group) was significantly higher in the laparoscopic-assisted group than in the open group (18.5% vs 9.5%; p = 0.03). It was noted that the incidence of port tumor recurrence (PTR) in the LAS group dropped significantly from the first to the latter three trials (second, third, and fourth trials combined) (36.1% vs 13.5%; p < 0.006) while it did not change significantly in the OS group. In the latter three trials, there was no significant difference in the number of animals with PTR between the LAS and the OS group (13.5% vs 9.8%; p = 0.43). CONCLUSIONS: Overall, there was no significant difference between the OS and the LAS groups in number of animals with port tumor recurrence or subcostal wound tumor recurrence. However, there were more port tumors in the laparoscopic-assisted group. The reasons for these findings are unclear. The laparoscopic mobilization was quite difficult; it required excessive splenic manipulation, which may have liberated tumor cells from the primary lesion and facilitated port tumor formation. With increased experience, less manipulation was required to complete the mobilization. Of note, the incidence of port tumors in the LAS group decreased significantly from the first to the subsequent three trials; therefore, it is possible that surgical technique is a factor in port tumor formation. The CO2 pneumoperitoneum may also be a factor, but this seems less likely.
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Neoplasias Abdominales/etiología , Adenocarcinoma/cirugía , Competencia Clínica , Laparoscopía/efectos adversos , Siembra Neoplásica , Esplenectomía , Neoplasias del Bazo/cirugía , Animales , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Neumoperitoneo Artificial , Punciones , Esplenectomía/métodosRESUMEN
BACKGROUND: Our laboratory and others have previously demonstrated that tumors grow larger and are more easily established following laparotomy than after CO(2) pneumoperitoneum. The etiology of increased tumor growth after surgery is unknown. We hypothesized that, following laparotomy, a serum soluble factor(s) is generated that causes tumors to proliferate more rapidly. The purpose of the current study was to determine if in vitro tumor cells proliferate faster when incubated with serum from laparotomized mice than cells incubated with sera from mice who have undergone CO(2) pneumoperitoneum or anesthesia alone. METHODS: In the first experiment, female Balb/C mice (n = 84) were randomly divided into the following three groups: (a) control (AC), (b) CO(2) insufflation (INS), and (c) laparotomy (OPEN). The AC mice underwent no procedure. The INS group underwent CO(2) pneumoperitoneum at 4-6 mmHg for 20 min. The OPEN group had a midline incision from xiphoid to pubis. The serum of seven mice from each group were collected on postoperative days (POD) 1, 2, 4, and 7 via a cardiac puncture. The sera at each time point for each group were pooled. Twenty thousand C-26 colon cancer cells were incubated separately in growth media containing 10% mouse serum from each group (seven determinations/group) at each time point. In the second experiment, female Balb/C (n = 30) mice were divided into AC and OPEN groups. On POD4, sera were collected and pooled. Three separate studies were performed for the second experiment. In the first study, tumor cells were incubated with 10% AC sera or varying concentrations of OPEN mice sera (4-10%). In the second study, aliquots of sera from the OPEN group mice were then heated at 100 degrees C for 1 or 5 min. Tumors were then incubated separately in media with 10% AC, OPEN, or heated OPEN group sera. In the third study, aliquots of sera from the OPEN group mice were dialyzed against PBS through a 3.5-kD or an 8-kD dialysis membrane tubing for 24 h. Tumors were then incubated separately in media with 10% AC, OPEN, or dialyzed OPEN group sera. For both experiments, tumor proliferation was determined and compared between groups after 72 h of incubation. RESULTS: Tumor cells incubated with POD2 and POD4 sera from OPEN group mice proliferated twice as fast as those incubated with sera from either AC or INS group mice. The difference in proliferation was maximal on POD4 and started to decline by POD7. Proliferative activity from the OPEN group sera decreased significantly when heated for 1 min and was completely ablated after 5 min of heating. Proliferative activity from the OPEN group sera was completely ablated after dialysis. CONCLUSIONS: We conclude that there is a serum-soluble factor(s) present postoperatively that stimulates tumors to grow significantly faster after laparotomy. The mitogenic effect of laparotomized mice sera is dilutable. It is uncertain whether the factor is heat labile, since heating most likely destroys other necessary proteins in the sera. The size of the factor is undeterminable using the dialysis method. Further efforts to identify these factors are currently underway.
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Sustancias de Crecimiento/sangre , Laparotomía , Neoplasias Experimentales/patología , Animales , Femenino , Calor , Ratones , Ratones Endogámicos BALB C , Mitosis , Peso Molecular , Neumoperitoneo Artificial , Células Tumorales CultivadasRESUMEN
PURPOSE: Our laboratory has demonstrated that significantly more cell-mediated immunosuppression occurs after full laparotomy than after either anesthesia control or carbon dioxide (CO2) pneumoperitoneum. We further demonstrated that the postoperative immunosuppression is related to the length of the incision. Other investigators believe that the immunosuppression observed after laparotomy is caused by peritoneal exposure to small amounts of lipopolysaccharide found in circulating air. They believe that the better-preserved immune function associated with laparoscopic surgery results from the avoidance of air contamination of the peritoneal cavity. To investigate this hypothesis, we determined and compared postoperative lymphocyte proliferation rates after (a) laparotomy in room air, (b) laparotomy in a CO2 chamber, (c) CO2 insufflation in a murine model, and (d) anesthesia alone. METHODS: Female C3H/He mice (n = 21) were divided randomly into four groups: (a) anesthesia control, (b) air laparotomy, (c) CO2 laparotomy, and (d) CO2 insufflation. The control mice underwent no procedure. The group 2 animals underwent a full midline incision (xiphoid to pubis) and exposure to room air for 20 min and then were clipped closed. The group 3 mice underwent a full midline incision in a sealed CO2 chamber for 20 min, and the group 4 mice insufflation with CO2 gas at 4 to 6 mm Hg for 20 min. Splenocytes were harvested from all the animals on day 2 after the interventions. Lymphocyte proliferation then was assessed using the nonradioactive colorimetric MTS/PMS system 72 h after concanavalin-A stimulation. RESULTS: There was no significant difference in lymphocyte proliferation between the air and CO2 laparotomy groups. Lymphocyte proliferation in the anesthesia control and CO2 insufflation groups was significantly higher than in both the air laparotomy (p<0.05) and CO2 laparotomy (p<0.05) groups (p values by Tukey-Kramer test). There was no significant difference between the anesthesia control and CO2 pneumoperitoneum groups. CONCLUSIONS: Our results suggest that full laparotomy performed in a sealed CO2 chamber compared to room air laparotomy resulted in similar suppression of lymphocyte proliferation. Furthermore, no significant suppression of lymphocyte proliferation was observed in the CO2 pneumoperitoneum group. These results, with regard to lymphocyte proliferation rates, refute the hypothesis that postoperative immunosuppression is related to air exposure and support the alternative hypothesis that immunosuppression is related to incision length.
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Aire , Dióxido de Carbono , Laparotomía/métodos , Activación de Linfocitos , Linfocitos/inmunología , Neumoperitoneo Artificial/métodos , Animales , División Celular , Femenino , Tolerancia Inmunológica , Inmunidad Celular , Ratones , Ratones Endogámicos C3HRESUMEN
BACKGROUND: Our laboratory has previously demonstrated that cell-mediated immune function is significantly more suppressed after both laparotomy and laparoscopic-assisted bowel resection than after peritoneal insufflation or open bowel resection, as assessed by delayed-type hypersensitivity (DTH) response. The purpose of this study was to further evaluate cell-mediated immunity by examining lymphocyte proliferation rates after laparotomy vs CO(2) insufflation. METHODS: Female Balb/C mice (n = 75) were randomly divided into the following three groups: (a) anesthesia control (A/C), (b) CO(2) insufflation (INS), and (c) sham laparotomy (OPEN). The A/C group mice underwent no procedure. The INS group underwent insufflation with CO(2) gas at 4-6 mmHg for 20 min. The OPEN group underwent a midline incision from xiphoid to pubic symphysis, which was clipped closed after 20 min. Splenocytes were obtained via splenic harvest and lymphocyte isolation on postoperative days (POD) 1, 2, 3, 4, and 8. Lymphocyte proliferation was determined by a nonradioactive colorimetric MTS/PMS assay 72 h after concanavalin A stimulation. RESULTS: The laparotomy group's lymphocyte proliferation rates were significantly lower than both the control and the insufflation groups on POD 2, POD 3, and POD 4. On POD 1 and POD 8, there were no significant differences in lymphocyte proliferation among the three groups. No differences were found between the control and insufflation groups at any point. CONCLUSIONS: After stimulation, lymphocytes proliferate at a lower rate after laparotomy than after CO(2) insufflation. Significant differences in lymphocyte proliferation rates between groups persist at least through POD 4. By POD 8, the mean lymphocyte proliferation rate in the laparotomy group was back to the baseline level. Our results suggest greater immunosuppression after sham laparotomy than after CO(2) insufflation.
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Hipersensibilidad Tardía/inmunología , Laparotomía , Linfocitos/inmunología , Neumoperitoneo Artificial , Animales , División Celular , Femenino , Inmunidad Celular , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Our laboratory has previously used pig and rat models to demonstrate that delayed-type hypersensitivity (DTH) response to an antigen challenge is suppressed following laparotomy compared to insufflation. The purpose of this study was to develop a practical and reliable mouse DTH model that could be used in future studies to test immunomodulating drugs and therapies. METHODS: Female C3H/HeN mice (n = 100) were given three serial DTH challenges of 25 microl of 4 mg/ml phytohemagglutinin (PHA) 12 days before the test procedure, immediately following the test procedure, and on the 2nd postoperative day. All challenges were administered via subcutaneous injection in alternating footpads. The thickness of the footpad was determined with electronic calipers immediately prior to injection and 24 h following injection in a blinded fashion. The difference in thickness represents the response. On the day of the procedure, mice were randomized into the following three groups: (a) control (AC), (b) insufflation (INS), and (c) open (OPEN). AC mice underwent no procedure. INS mice underwent CO(2) insufflation at 2-4 mmHg for 20 min. OPEN mice underwent a midline incision from xiphoid to pubis that was closed after 20 min. Data were analyzed using ANOVA and Tukey-Kramer tests to determine differences between groups. RESULTS: Preoperatively, there were no significant differences among the three groups. On POD1, the OPEN group had significantly less response than both the AC and INS groups. On POD3, there were significant differences between the OPEN group and both the INS and AC groups. There was no significant difference between the AC and INS group at any time. CONCLUSIONS: In conclusion, a DTH mouse model has been established that allows serial assessment of cell-mediated immune function. This model can be used to study immune function after open and minimal access procedures in a simple and cost-effective manner.
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Modelos Animales de Enfermedad , Hipersensibilidad Tardía/inmunología , Laparotomía , Neumoperitoneo Artificial , Animales , Estudios de Evaluación como Asunto , Femenino , Inmunidad Celular , Ratones , Ratones Endogámicos C3H , Distribución AleatoriaRESUMEN
PURPOSE: The development of port-wound tumor recurrences has raised questions regarding the safety of laparoscopic methods for the resection of malignancies. The cause and the incidence of abdominal-wall tumor recurrences remain unknown. It is also not clear how to avoid or lower the incidence of port-tumor recurrences. The purpose of the current study was to determine the impact of abdominal irrigation with povidone-iodine on the port-wound tumor incidence in a murine model. METHODS: A splenic tumor model was used for this study. To establish splenic tumors, female BALB/c mice (N = 48) were given subcapsular splenic injections of a 0.1 ml suspension containing 10(5) C-26 colon adenocarcinoma cells via a left-flank incision at the initial procedure. Seven days later, the animals with isolated splenic tumors (100 percent) were randomly assigned to one of three groups: 1) control, 2) saline irrigation (saline), or 3) povidone-iodine irrigation. All animals underwent laparoscopic mobilization of the spleen using a three-port technique, intra-abdominal crushing of the tumor, followed by an extracorporeal splenectomy via a subcostal incision. No irrigation was performed for control group animals. In the saline irrigation group, the subcostal incision was closed and pneumoperitoneum was re-established. The abdominal cavity was irrigated with 5 ml of normal saline for 60 seconds before instrument removal. In the povidone-iodine irrigation group, similar abdominal irrigation was performed, using 0.25 percent povidone-iodine. Attempts were made to recover completely the irrigation for both irrigation groups. Seven days after the splenectomy, animals were killed and inspected for abdominal-wall tumor implants. RESULTS: There were significantly more animals with at least one port-tumor recurrence in the control group than in the povidone-iodine group (P = 0.007). Although not statistically significant, the number of animals with port-wound tumors was higher in the saline group than in the povidone-iodine group (P < 0.08). There was no significant difference between the saline group and the control group. When each port site was considered independently, the incidence of port-wound tumors (number of ports with tumors per total number of ports) was significantly lower in the povidone-iodine group than in both the control (P = 0.00001) and saline groups (P = 0.03). The incidence of port-wound tumors was also significantly lower in the saline group compared with the control group incidence (P = 0.03). CONCLUSIONS: Abdominal irrigation with dilute povidone-iodine solution significantly reduced the number of animals with port-tumor recurrences. Abdominal irrigation with saline was also effective in reducing the incidence of port-wound tumor formation when each port was considered separately. However, povidone-iodine irrigation was much more effective than saline irrigation in preventing port-wound tumor formation.
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Antiinfecciosos Locales/uso terapéutico , Laparoscopía/efectos adversos , Siembra Neoplásica , Povidona Yodada/uso terapéutico , Esplenectomía/métodos , Irrigación Terapéutica , Adenocarcinoma/cirugía , Animales , Estudios de Evaluación como Asunto , Femenino , Ratones , Ratones Endogámicos BALB C , Proyectos Piloto , Distribución Aleatoria , Neoplasias del Bazo/cirugía , Células Tumorales CultivadasRESUMEN
INTRODUCTION: Although some have suggested that certain vitamins or calcium supplements may reduce adenoma recurrence, our own prior retrospective study found no such effects. The purpose of this case-control study was to further investigate whether regular vitamin or calcium supplement intake influenced the incidence of recurrent adenomatous polyps in patients with previous neoplasia who were undergoing follow-up colonoscopy. METHODS: This study enrolled 1,162 patients who underwent colonoscopy by one of three surgeons at Columbia-Presbyterian Medical Center in New York City between March 1993 and February 1997. Of these patients 448 (250 males) had a previous diagnosis of colorectal neoplasia (cancer, adenomas, or dysplasia). Of these, 183 (40.8 percent) had an adenoma at the index colonoscopy. Information was collected on personal and family history of colonic diseases, cigarette smoking, medication, and vitamin and micronutrient supplement usage on a questionnaire that was completed by the patients before the colonoscopy. Odds ratios were obtained by unconditional logistic regression analysis, adjusting for age and gender, and used adenoma recurrence at index colonoscopy as the outcome. RESULTS: The mean interval between colonoscopic examinations was 37 months for the recurrent adenoma group and 38 months for the nonrecurrent group of patients (P = not significant). In this case-control study we found a protective effect for the use of vitamin supplements in general (any vitamin) on the recurrence of adenomas (odds ratio, 0.41; 95 percent confidence interval, 0.27-0.61). Specifically, this protective effect was observed for the use of multivitamins (odds ratio, 0.47; 95 percent confidence interval, 0.31-0.72), vitamin E (odds ratio, 0.62; 95 percent confidence interval, 0.39-0.98), and for calcium supplementation (odds ratio, 0.51; 95 percent confidence interval, 0.27-0.96). Nonsignificant protective effects were noted for carotene/vitamin A, vitamin D, and vitamin C. CONCLUSIONS: The use of multivitamins, vitamin E, and calcium supplements were found to be associated with a lower incidence of recurrent adenomas in a population of patients with history of previous colonic neoplasia. Prospective, randomized trials are needed to better assess the impact of these agents and to determine whether the use of these supplements is associated with a protective effect against recurrent adenomas.
Asunto(s)
Pólipos Adenomatosos/prevención & control , Calcio/administración & dosificación , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/prevención & control , Micronutrientes , Neoplasias Primarias Múltiples , Vitaminas/administración & dosificación , Estudios de Casos y Controles , Colonoscopía , Humanos , Masculino , Recurrencia Local de Neoplasia , Oportunidad Relativa , Estudios Retrospectivos , Encuestas y Cuestionarios , Vitamina E/administración & dosificaciónRESUMEN
BACKGROUND: Many cellular elements responsible for wound healing are affected by laparotomy. The aim of this study was to evaluate the effects of laparotomy and CO2 pneumoperitoneum on wound healing. METHODS: Male Sprague Dawley rats were randomly assigned to one of three experimental groups. Anesthesia control rats underwent no procedure. Pneumoperitoneum group rats were insufflated with CO2 gas. Laparotomy group rats underwent a 7-cm midline laparotomy incision. The interventions were 30 min long. For the incisional study (n = 30), a 4-cm dorsal full-thickness skin incision was made on each rat and then closed with staples. On postoperative days 7 and 14, an equal number of rats were sacrificed from each group, and wound tensile strength measurements were performed. For the excisional study (n = 45), each group of 15 rats underwent a 2-cm diameter circular dorsal full-thickness skin excision. Blinded measurements of wound area were performed every other day until wounds closed. RESULTS: Wound tensile strength values were not significantly different among experimental groups at either time point. The study had a power of 80% to find a 30% difference at POD 7 and a power of 80% to find a 23% difference at POD 14 to a confidence level of p < 0.05. Wound contraction data from the excisional model were analyzed with the Generalized Estimation Equations statistical approach. When we modeled the treatment group as a covariate, no statistical difference was found between groups, demonstrating equal slopes across time. CONCLUSIONS: From the results of these studies, we conclude that wound healing in this model is not significantly diminished following laparotomy or peritoneal insufflation, as compared to anesthesia control.
Asunto(s)
Laparotomía , Neumoperitoneo Artificial , Cicatrización de Heridas , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Resistencia a la TracciónRESUMEN
BACKGROUND: We investigated the ability of pressurized CO2 gas to aerosolize B16 melanoma (B16) tumor cells in an in vitro model. METHODS: The experimental apparatus consisted of an 18.9-L plastic cylindrical vessel and a compliant latex pouch was attached to the top. Two 5-mm ports penetrated the vessel; insufflation and desufflation were carried out through them. A culture dish containing 20 million B16 cells in liquid culture media was placed at the base within the container. In the first experiment, the vessel was insufflated with CO2 gas to a static pressure of 15 or 30 mm Hg with the outflow port closed. After 10 min, the outflow port was opened and the gas was desufflated through a collecting device containing sterile culture medium. In a second experiment, a continuous flow of CO2 through the vessel was maintained after a pressure of 15 or 30 mm Hg was established. A total of 10 L CO2 was cycled through the vessel. In both experiments, 24 determinations were carried out at each pressure. Each experimental culture dish was microscopically scanned for 2 weeks for the presence of tumor cells. The third and fourth experiments tested for the presence of aerosolized nonviable tumor cells in the expelled gas. Using the model described above, after 10 mins of 30 mm Hg static pressure, the CO2 gas was expelled directly onto a glass slide and cytofixed. Alternately, after 10 mins at 30 mm Hg static pressure, the gas was expelled through a saline-filled Soluset (Abbott Laboratories), centrifuged, and the residue cytofixed onto a glass slide. Each of the five slides per experiment were examined microscopically for the presence of cells. RESULTS: In the first and second experiments, no cells or growth were observed in any of the 96 experimental dishes. In experiments three and four, no cells were detected on any of the slides. CONCLUSIONS: It was not possible with this model to aerosolize tumor cells in a pressurized CO2 environment. Our results suggest that aerosolization of tumor cells is not the mechanism of port site recurrences after laparoscopic surgery for malignant disease.
Asunto(s)
Aerosoles , Melanoma Experimental , Dióxido de Carbono , Técnicas In Vitro , Laparoscopía/efectos adversos , Siembra Neoplásica , Neumoperitoneo Artificial/efectos adversos , Células Tumorales CultivadasRESUMEN
In response to the relative lack of success in reaching students with eating disorders, a campus-wide Eating Concerns Committee undertook to understand the needs of these students and to advise them on appropriate services. Because social pressure to be thin is one important precursor to eating disorders and because sharing concerns is so difficult and so important, the committee used the college's computer bulletin board system to create a forum for students to discuss political, social, and personal issues about body image, food, and eating. After a cautious start, the dialogue developed intensity and became a lively tool for asking and receiving support and for sharing feelings, ideas, and concerns.
Asunto(s)
Imagen Corporal , Redes de Comunicación de Computadores , Trastornos de Alimentación y de la Ingestión de Alimentos/prevención & control , Apoyo Social , Servicios de Salud para Estudiantes/métodos , Femenino , Humanos , Massachusetts , Grupo ParitarioRESUMEN
In recent theoretical formulations, researchers have pointed out that relationships are integral to women's psychological development and identity. Alcohol plays a role for women in seeming to facilitate relationships and in self-medicating when relationships are not mutual or are abusive. Theories about women's psychological development can also be applied to designing prevention strategies by emphasizing relational material, affective content, and intuitive learning styles. An interactive style is strongly encouraged and is demonstrated in a prevention program that seeks to engage the audience emotionally. Components of the prevention model are outlined, including emphasizing the use of peers in design and implementation, strengthening support systems and relational ties, and valuing empathic and intuitive skills. Suggestions are also offered for applying these components to the culture of the college community.
Asunto(s)
Alcoholismo/prevención & control , Estudiantes/psicología , Mujeres/psicología , Alcoholismo/psicología , Femenino , Humanos , Relaciones Interpersonales , Masculino , Prevención Primaria , Psicoterapia de Grupo , Apoyo Social , UniversidadesRESUMEN
Little attention has been paid to college women's drinking, partly because women drink less than college men do, partly because they are less likely to get into trouble with the authorities, and partly because women have only recently been understood to develop differently and to have different needs from those of men. Recent theories stress the importance of relationships in women's development, identity, and self-esteem and failures in mutuality and intimacy as contributing to subjective pain and dysfunction. These theoretical formulations suggest a new understanding for women's use of alcohol, one that emphasizes drinking as a way of being with others, of seeking acceptance from peers, and of numbing the pain that comes from relationships that do not work. Women are at greater risk of being abused when drinking, and women who have been sexually or physically abused are at greater risk for abusing alcohol.
Asunto(s)
Consumo de Bebidas Alcohólicas , Estudiantes/psicología , Mujeres/psicología , Adaptación Psicológica , Adulto , Mecanismos de Defensa , Femenino , Homosexualidad/psicología , Humanos , Relaciones Interpersonales , Masculino , Desarrollo de la Personalidad , Conducta Social , Estrés Psicológico/psicologíaRESUMEN
Nalbuphine and fentanyl were compared as analgesic components of intravenous conscious sedation with diazepam in a double-blind, prospective trial of 50 patients undergoing elective oral surgery. Subjects were evaluated for intensity of pain, pain relief, sedation, anxiety, recall, and vital signs at systematic observation points intraoperatively and postoperatively. At the conclusion of surgery, 88% who received nalbuphine and 87% treated with fentanyl indicated complete pain relief. One observed adverse reaction was attributed to the combination of fentanyl and the sedative component diazepam. No statistically significant differences were observed between nalbuphine and fentanyl treatments.
Asunto(s)
Anestesia Dental , Diazepam/administración & dosificación , Fentanilo/administración & dosificación , Morfinanos/administración & dosificación , Nalbufina/administración & dosificación , Dolor Postoperatorio/prevención & control , Medicación Preanestésica , Adulto , Método Doble Ciego , Quimioterapia Combinada , Estudios de Evaluación como Asunto , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios ProspectivosRESUMEN
We have observed two cases of human infection with intraerythrocytic protozoa. The organisms appeared to be in the Entopolypoides group, which had not previously been associated with human infection. One patient was asplenic. Both patients had hepatic dysfunction, and their serum samples contained blocking factors that interfered in vitro with the stimulation of normal lymphocytes by phytohemagglutinin. It appears that in humans, as well as in experimental animals, host factors are important in resistance to infection by intraerythrocytic parasites. These factors include the presence of a spleen and cell-mediated and humoral immunities. Possibly similar infections will be observed in patients with other impairments of T-cell function, such as those induced by malignancy, thymic dysfunction, or immunosuppressive drugs.
Asunto(s)
Babesiosis/inmunología , Lectinas/farmacología , Hepatopatías/complicaciones , Activación de Linfocitos , Adulto , Animales , Anticuerpos , Babesia/anatomía & histología , Babesia/inmunología , Babesiosis/transmisión , Cricetinae , Eritrocitos/parasitología , Humanos , Inmunidad , Inmunidad Celular , Hepatopatías/inmunología , Masculino , Persona de Mediana Edad , Ratas , Bazo/inmunología , Linfocitos T/fisiologíaRESUMEN
Seven investigations of suspected foci of amebiasis between October 1971 and June 1974 lead to three conclusions. (1) A number of laboratories have vastly overdiagnosed amebiasis and have reported leukocytes in stools as Entamoeba histolytica. Two laboratories found to be in error were in community hospitals, and one was at a teaching hospital associated with a medical school and a school of public health. These three laboratories had been diagnosing more than 1200 cases of amebiasis a year for 20 years. (2) When amebiasis does occur, it is likely to be misdiagnosed. In one outbreak with four cases and three deaths, amebiasis was not diagnosed until two patients had died and another was critically ill. Sporadic cases may be mistakenly diagnosed as ulcerative colitis and inappropriately treated with steroids. (3) Foci of endemic amebiasis continue to exist in the United States, both in institutions and in noninstitutional settings.