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Biomedical subjects

Angelo Nespoli

Publications and source records attributed to Angelo Nespoli.

7 recordsLinked to original sources

Impact of postoperative infections on survival in colon cancer patients.

PURPOSE: We investigated the prognostic significance of postoperative infections for the outcome of 192 patients with colon cancer. METHODS: The 5-year survival rates were analyzed by the Kaplan-Meier technique. Univariate and multivariate analyses were done to evaluate prognostic variables using Cox's proportional hazard model. RESULTS: Forty-three patients developed deep incisional or organ/space surgical site infections. The groups with and without infection were comparable. Multivariate analysis showed that only Dukes' stage (p=0.048) and postoperative infection (p=0.011) were independently associated with outcome. In patients with infective complications, the survival rate was significantly lower than in subjects without infection (log rank p=0.0004). CONCLUSIONS: These results stress the importance of evaluating variables other than the classical tumor stage in predicting long-term cancer outcome.

Colectomy↗

Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells.

The control of damaging inflammation by the mucosal immune system in response to commensal and harmful ingested bacteria is unknown. Here we show epithelial cells conditioned mucosal dendritic cells through the constitutive release of thymic stromal lymphopoietin and other mediators, resulting in the induction of 'noninflammatory' dendritic cells. Epithelial cell-conditioned dendritic cells released interleukins 10 and 6 but not interleukin 12, and they promoted the polarization of T cells toward a 'classical' noninflammatory T helper type 2 response, even after exposure to a T helper type 1-inducing pathogen. This control of immune responses seemed to be lost in patients with Crohn disease. Thus, the intimate interplay between intestinal epithelial cells and dendritic cells may help to maintain gut immune homeostasis.

Cell Differentiation↗

Lymphocyte counts independently predict overall survival in advanced cancer patients: a biomarker for IL-2 immunotherapy.

Interleukin-2 (IL-2) targets cells bearing IL-2 receptors and induces different degrees of lymphocytosis. This study retrospectively evaluated whether lymphocytosis, in addition to clinical characteristics at baseline and to tumor objective response, may predict overall survival in metastatic renal cell carcinoma patients who received IL-2 subcutaneously (s.c.). Overall survival, clinical characteristics, tumor response, and total lymphocyte count at baseline and during the first treatment cycle of 266 advanced renal cell cancer patients, treated with 1 of 4 different first-line s.c. IL-2-based protocols, were studied using the Cox multivariate analysis. Median IL-2 cumulative dose and length of treatment (+/-SD) were 232 +/- 282 x 10(6)/m(2) in 7 +/- 5.9 weeks, respectively. Median overall survival (os) was 13.1 months (range 0.7-86.9+) in all. Tumor outcome consisted of: 9 CR (3%) (os = NR); 35 PR (13%) (os = 19.7 months.); 117 SD (44%) (os = 15.1 months); 105 PD (39%) (os = 6.4 months). Median lymphocyte counts were 1400/mm(3) at baseline (25th-75th, 900-1900/mm(3)) and 3600/mm(3) as a maximum value (25th-75th, 2600-4800/mm(3)). Death risk significantly decreased by 11% for each 1,000 lymphocytes/mm(3) (RR 0.89; 95% CI 0.82-0.97), after correcting for clinical characteristics (PS ECOG 0 versus > or =1, time from primary diagnosis > or =2 years versus <2 years, number of metastatic sites 1 versus >1) and tumor response (CR, PR). A two-step bootstrapping procedure confirmed such predictive performance. Lymphocyte count monitoring represents a biomarker of the host response to subcutaneous IL-2 treatment useful for multimodal clinical assessment, as it predicts overall survival in advanced cancer patients independently from tumor response and from main clinical characteristics.

Adult↗

Correlation between postoperative infections and long-term survival after colorectal resection for cancer.

INTRODUCTION: Predicting long-term survival and cancer recurrence in patients with colorectal cancer is difficult because of the many factors that may affect the prognosis. This study investigated the prognostic significance of postoperative infections for patient outcome. METHODS: From an electronic database we selected 192 patients undergoing elective radical surgery for Dukes' stage B and C colorectal adenocarcinoma. The five-year survival rates were analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were carried out to evaluate the potential prognostic variables using the Cox proportional hazard model. RESULTS: Forty-three patients developed deep incisional or organ/space surgical site infections, while the remaining 149 were complication free. The two groups were comparable for baseline, surgical and histopathological characteristics. At univariate analysis, Dukes' stage and infections were negative prognostic factors, while peritumoral infiltration of lymphocytes and eosinophils and fibrotic tissue appeared as protective variables. However, multivariate analysis showed that only Dukes' stage (P = 0.048) and occurrence of postoperative infectious complications (P = 0.011) were independently associated with outcome. In patients with infectious complications, the survival rate was significantly lower than in patients without infections (log-rank = 0.0004). CONCLUSIONS: The present results suggest the importance of evaluating other variables besides tumor stage in the prediction of long-term outcome. In prognostic studies more attention should be paid to postoperative infections.

Aged↗

Effects of IL-2 preoperative immunotherapy on surgery-induced changes in angiogenic regulation and its prevention of VEGF increase and IL-12 decline.

BACKGROUND/AIMS: IL-2 preoperative immunotherapy has been proven to abrogate surgery-induced immunosuppression in cancer patients. In contrast, at present there are no data about the possible influence of IL-2 on angiogenesis-related molecular changes determined by the surgical operation. At present, it is known that VEGF (vascular endothelial growth factor) is the main endogenous angiogenic factor, whereas the antitumor cytokine IL-12 has appeared to play an anti-angiogenetic role. On this basis, a study was planned to evaluate the influence of IL-2 presurgical immunotherapy on the perioperative changes in VEGF and IL-12 secretions. METHODOLOGY: The study was performed on 30 colorectal cancer patients undergoing radical surgery, who were randomly chosen to be treated with or without preoperative immunotherapy of IL-2 (12 million IU/day subcutaneously for 3 consecutive days prior to surgery). Serum levels of VEGF and IL-12 were measured by ELISA for blood samples collected before surgery, and at days 3, 7 and 10 of the postoperative period. RESULTS: VEGF mean concentrations progressively and significantly increased during the postoperative period in patients treated with surgery alone. Mean values of VEGF were enhanced also in patients pretreated with IL-2, but VEGF increase observed in the IL-2 group was delayed, more transient and significantly lower with respect to that found in controls. IL-12 mean concentrations significantly decreased during the postoperative period only in the control patients, whereas in the IL-2-treated patients IL-12 postoperative mean values were not significantly lower than those found before surgery. CONCLUSIONS: This preliminary study would suggest that IL-2 preoperative immunotherapy may abrogate surgery decline in IL-12 levels and reduce, although not completely prevent, VEGF increase during the postoperative period in surgically treated cancer patients. These results would suggest that IL-2 presurgical immunotherapy may counteract surgery-induced stimulation of the angiogenesis, by either opposing the decline in blood levels of the anti-angiogenetic cytokine IL-12, or reducing the increase in those of the angiogenic factor VEGF.

Aged↗

[Multiple abdominal trauma: therapeutical options].

OBJECTIVE: To revise a series of multiple abdominal trauma in order to evaluate the type of diagnosis process and therapy undertaken, the complication and patient survival rates. PATIENTS: Three hundred ten patients of whom 294 (94.8%) with a single abdominal organ injury associated or not with trauma of extra-abdominal organs (thorax, mediastinum, brain, bone) and 16 patients with a multiple abdominal injury (2 or more organs) associated or not with trauma of extra-abdominal organs. Age, gender, vital parameters, injury dynamics, number of organs, site of injury, Injury Severity Score (ISS), Abdominal Trauma Index (ATI) and Glasgow Coma Scale (GCS) have been recorded at admission. RESULTS: Multiple abdominal trauma represent 5% of all abdominal trauma. All trauma were closed ones: 14 street accident and 2 precipitations. A non operative management was undertaken in 6 patients, successfully completed in 2, while 4 patients required a surgical intervention to control bleeding within 12 hours of observation. Ten patients underwent immediate operation for unstable vital signs. The mean number of abdominal organs damaged was 2.8/patient. The mortality rate was 43.7% (7/16). All patients died during surgery. By comparing dead and surviving patient, initial haemodynamics and severity of ISS, GCS, and ATI scores were significant negative prognostic factors. The median length of hospitalisation of survivors was 12 days. CONCLUSIONS: Non operative management of multiple abdominal injury seems to be feasible in a small percentage and possibly only in selected cases.

Abdominal Injuries↗

Pre-operative immunoprophylaxis with interleukin-2 may improve prognosis in radical surgery for colorectal cancer stage B-C.

Cancer-associated immunodeficiency is seriously worsened by surgical trauma. Short-term pre-operative interleukin-2 (IL-2) administration abolished post-operative immunodeficiency. The effects of a pre-operative IL-2 immunotherapy on the prognosis of colorectal cancer patients (Dukes' stages B and C), undergoing radical surgery, are reported. The study included, after post-operative stratification, 86 consecutive patients with colorectal cancer Dukes' stage B (57) and C (29), undergoing radical laparotomic surgery, randomised to be treated pre-operatively, with or without a short-term course of subcutaneous (s.c.) IL-2 immunotherapy. Human recombinant IL-2 was given s.c. at 6x10(6) I.U. twice daily pre-operatively for 3 consecutive days. Surgery was performed 36 hours after the last IL-2 injection. Dukes' C patients of both groups received standard adjuvant chemotherapy consisting of 5-FU plus folates and radiotherapy for rectal cancer patients. After a median follow-up of 54 months (range 18-86), the progression rate was significantly lower in patients pre-treated with IL-2 than in controls: 9/42 (21.4%) IL-2 group vs. 19/44 (43.1%) controls, (p <0.03). The positive effect of immunotherapy was detected both in the Dukes' B group, with 5/29 (17%) progression in the IL-2 group vs. 9/28 (32%) in controls, and Dukes' C patients with 4/13 (30%) vs. 10/16 (62%). This study shows that a 3-day pre-operative course of IL-2 immunotherapy may improve prognosis in patients with colorectal cancer at Dukes' stages B and C, as previously demonstrated in patients with more advanced disease. Therefore, the early activation of the antineoplastic immune system in the first post-operative days following a presurgical activation with IL-2 may counteract the growth of minimal residual disease and prevent late disease progression.

Adult↗