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BACKGROUND: This study investigated the efficacy of chemoradiotherapy (CRT) followed by durvalumab as neoadjuvant therapy of locally advanced rectal cancer. PATIENTS AND METHODS: The PANDORA trial is a prospective, phase II, open-label, single-arm, multicenter study aimed at evaluating the efficacy and safety of preoperative treatment with durvalumab (1500 mg every 4 weeks for three administrations) following long-course radiotherapy (RT) plus concomitant capecitabine (5040 cGy RT in 25-28 fractions over 5 weeks and capecitabine administered at 825 mg/m2 twice daily). The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the proportion of clinical complete remissions and safety. The sample size was estimated assuming a null pCR proportion of 0.15 and an alternative pCR proportion of 0.30 (α = 0.05, power = 0.80). The proposed treatment could be considered promising if ≥13 pCRs were observed in 55 patients (EudraCT: 2018-004758-39; NCT04083365). RESULTS: Between November 2019 and August 2021, 60 patients were accrued, of which 55 were assessable for the study's objectives. Two patients experienced disease progression during treatment. Nineteen out of 55 eligible patients achieved a pCR (34.5%, 95% confidence interval 22.2% to 48.6%). Regarding toxicity related to durvalumab, grade 3 adverse events (AEs) occurred in four patients (7.3%) (diarrhea, skin toxicity, transaminase increase, lipase increase, and pancolitis). Grade 4 toxicity was not observed. In 20 patients (36.4%), grade 1-2 AEs related to durvalumab were observed. The most common were endocrine toxicity (hyper/hypothyroidism), dermatologic toxicity (skin rash), and gastrointestinal toxicity (transaminase increase, nausea, diarrhea, constipation). CONCLUSION: This study met its primary endpoint showing that CRT followed by durvalumab could increase pCR with a safe toxicity profile. This combination is a promising, feasible strategy worthy of further investigation.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Capecitabina/farmacología , Capecitabina/uso terapéutico , Estudios Prospectivos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Quimioradioterapia/efectos adversos , Diarrea/inducido químicamente , Transaminasas/uso terapéuticoRESUMEN
BACKGROUND: Coaching is maturing as a strategy for surgeons' continuous professional development in different types of surgery. Laparoscopic total mesorectal excision (LAP TME) is one of the recognized difficult procedures in colorectal surgery. Aim of this trial is to introduce the surgical coaching as a tool for a continuous technical education of LAP TME for cancer in a consultant surgeon carrier. METHODS: Twelve Italian colorectal surgeons were enrolled as trainees in the AIMS Academy rectal cancer surgical coaching project and attended a face-to-face 90-min surgical coaching on a pre-edited 45-min-long video of a laparoscopic proctectomy according to pre-determined guidelines. At the end of the coaching, all mentors were asked to fill a questionnaire evaluating the trainee's skills. All trainees had to fill a post-coaching questionnaire addressing the appropriateness of the coaching with respect to their actual level. RESULTS: Trainees were more confident in performing the extra-pelvic part of the surgical procedures compared to the intra-pelvic dissection. The most challenging steps according to the trainees were the seminal vesicles identification and the pelvic floor dissection. Mentors found the trainees quite confident in the approach to the vascular structures, lymphadenectomy, stapler utilization and bleeding control. The sharpness and the efficacy of the dissection, the dissection of the surgical planes and the anastomosis fashioning were reported at a lower level of confidence. The higher grade of satisfaction reported by the trainee came from the attention that the mentors demonstrated towards them, from the availability of the mentors to take into consideration the surgical issues raised and from the willingness to apply the suggestions received during their next proctectomies. CONCLUSIONS: The surgical coaching applied to LAP TME should be considered as an innovative tool for continuous professional development.
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Procedimientos Quirúrgicos del Sistema Digestivo , Laparoscopía , Tutoría , Neoplasias del Recto , Anastomosis Quirúrgica , Humanos , Masculino , Neoplasias del Recto/cirugíaRESUMEN
Colorectal cancer is a widely-recognized aging-associated disease. Recent advances in the care of senior colorectal cancer patients has led to similar cancer-related life expectancy for older patients when compared to their younger counterparts. Recent data suggests that onco-geriatric patients place as much value on maintenance of functional independence and quality of life after treatment as they do on the potential improvements in survival that a treatment might offer. As a result, there has been significant interest in the geriatric literature surrounding the concept of "functional recovery," a multidimensional outcome metric that takes into account several domains, including physical, physiologic, psychological, social, and economic wellbeing. This review introduces the concept of functional recovery and highlights a number of predictors of post-treatment functional trajectory, including several office-based tools that clinicians can use to help guide informed decision making surrounding potential treatment options. This review also highlights a number of validated metrics that can be used to assess a patient's progress in functional recovery after surgery. While the timeline of each individual's functional recovery may vary, most data suggests that if patients are to return to their pre-operative functional status, this could occur up to 6 months post-surgery. For those patients identified to be at risk for post-operative functional decline this review also delineates strategies for prehabilitation and rehabilitation that may improve functional outcomes.
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Neoplasias Colorrectales/cirugía , Evaluación Geriátrica/métodos , Cuidados Preoperatorios/métodos , Calidad de Vida , Recuperación de la Función/fisiología , Anciano , HumanosRESUMEN
BACKGROUND: Nutritional status (NS), though frequently affected in onco-geriatric patients, is no standard part of a geriatric assessment. The aim of this study was to analyse the association between a preoperatively impaired NS and geriatric domain impairments and adverse postoperative outcomes in onco-geriatric surgical patients. METHODS: 309 patients ≥70 years undergoing surgery for solid tumours were prospectively recruited. Nine screening tools were preoperatively administered as part of a geriatric assessment. NS was based on BMI, weight loss and food intake. Odds ratio's (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression analysis. The occurrence of 30-day adverse postoperative outcomes was recorded. RESULTS: At a median age of 76 years, 107 patients (34.6%) had an impaired NS. Decreased performance status and depression were associated with an impaired NS, when adjusted for tumour characteristics and comorbidities (ORPS>1 3.46; 95% CI 1.56-7.67. ORGDS>5 2.11; 95% CI 1.05-4.26). An impaired NS was an independent predictor for major complications (OR 3.3; 95% CI 1.6-6.8). Ten out of 11 patients who deceased had an impaired NS. CONCLUSION: An impaired NS is prevalent in onco-geriatric patients considered to be fit for surgery. It is associated with decreased performance status and depression. An impaired NS is a predictor for adverse postoperative outcomes. NS should be incorporated in a geriatric assessment.
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Evaluación Geriátrica , Neoplasias/cirugía , Estado Nutricional , Complicaciones Posoperatorias/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Anciano Frágil , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias/patología , Países Bajos , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Reino UnidoRESUMEN
AIM: The Surgical Task Force at SIOG (International Society of Geriatric Oncology) designed this survey to explore the surgical oncologists' approach toward elderly cancer patients. METHODS: A web-based survey was sent to all members of ESSO (European Society of Surgical Oncology) and SSO (Society of Surgical Oncology). RESULTS: Two hundred and fifty-one surgeons responded (11% response rate) with a main interest on breast (62.1%), colorectal (43%) and hepatobiliary (27.4%) surgery. Almost all surgeons (>90%) offer surgery regardless the patient's age; only 48% consider mandatory a preoperative frailty assessment. The American Society of Anesthesiologists (ASA) score, nutritional and performance status are most frequently used as screening tools; only 6.4% surgeons use Comprehensive Geriatric Assessment (CGA) in daily practice and collaboration with geriatricians is low (36.3%). If proven to be effective, the majority of surgeons (71%) is prepared to pre-habilitate patients for up to 4 weeks before surgery. One in two surgeons would not offer an operation to patients with impaired cognitive status; conversely, one in three would proceed to surgery regardless of the patient's cognitive status, if functional capacity is conserved. Quality of life and functional recovery are regarded as the most important endpoints in onco-geriatric surgery. Large "real life" prospective observational studies and randomized controlled trials are demanded. CONCLUSION: Age is not perceived as a limitation to surgery. Screening for frailty is limited. A thorough CGA is seldom used and collaboration with geriatricians is rather uncommon. There is a need for clinical investigations focusing on pre-habilitation and other strategies to achieve better functional recovery.
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Actitud del Personal de Salud , Neoplasias del Sistema Biliar/cirugía , Neoplasias de la Mama/cirugía , Neoplasias Colorrectales/cirugía , Cirugía Colorrectal , Evaluación Geriátrica , Geriatría , Comunicación Interdisciplinaria , Neoplasias Hepáticas/cirugía , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/complicaciones , Neoplasias de la Mama/complicaciones , Trastornos del Conocimiento/complicaciones , Neoplasias Colorrectales/complicaciones , Indicadores de Salud , Humanos , Neoplasias Hepáticas/complicaciones , Persona de Mediana Edad , Estado Nutricional , Calidad de Vida , Recuperación de la Función , Encuestas y CuestionariosRESUMEN
Epithelial-mesenchymal transition (EMT) process has a central role in tumor progression and metastases. Loss of cell-to-cell adhesiveness is a key step in EMT. In particular, E-cadherin and ß-catenin, components of the adherens junctions, play a strategic role. Accumulation of ß-catenin at cytoplasmic level following adherens junctions disruption, induces its translocation into the nucleus, where it binds to members of the TCF/LEF family of transcription factors. In particular, Lymphoid Enhancer-Binding factor 1 (LEF1) product can target genes involved in EMT. The aim of the present study was to evaluate the influence of CDH1 and CTNNB1 genes, coding for E-cadherin and ß-catenin respectively and LEF1 in a sample study of 140 Italian patients affected by colorectal cancer. An association study between four single nucleotide polymorphisms (rs11865026, rs11642413, rs13689, and rs10431923) of CDH1 and the disease did not provide statistically significant results. The gene expression analysis carried out for CDH1, CTNNB1 and LEF1 in 54 paired specimens from 27 patients provided evidence of a reduced expression of the first two in cancer tissues. We believe there may be a sort of cross regulation between the products of these two genes which closely interact in EMT activation and that such hypothesis should be further investigated in a greater number of cases.
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AIMS: The aim of this study was to investigate the predictive ability of screening tools regarding the occurrence of major postoperative complications in onco-geriatric surgical patients and to propose a scoring system. METHODS: 328 patients ≥ 70 years undergoing surgery for solid tumors were prospectively recruited. Preoperatively, twelve screening tools were administered. Primary endpoint was the incidence of major complications within 30 days. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. A scoring system was derived from multivariate logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was applied to evaluate model performance. RESULTS: At a median age of 76 years, 61 patients (18.6%) experienced major complications. In multivariate analysis, Timed Up and Go (TUG), ASA-classification and Nutritional Risk Screening (NRS) were predictors of major complications (TUG>20 OR 3.1, 95% CI 1.1-8.6; ASA ≥ 3 OR 2.8, 95% CI 1.2-6.3; NRS impaired OR 3.3, 95% CI 1.6-6.8). The scoring system, including TUG, ASA, NRS, gender and type of surgery, showed good accuracy (AUC: 0.81, 95% CI 0.75-0.86). The negative predictive value with a cut-off point >8 was 93.8% and the positive predictive value was 40.3%. CONCLUSIONS: A substantial number of patients experience major postoperative complications. TUG, ASA and NRS are screening tools predictive of the occurrence of major postoperative complications and, together with gender and type of surgery, compose a good scoring system.
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Tamizaje Masivo , Neoplasias/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Femenino , Anciano Frágil/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Procedimientos Quirúrgicos Operativos/efectos adversosRESUMEN
OBJECTIVE: ADAMTS5 (aggrecanase-2) has been demonstrated to be crucial in the development of osteoarthritis (OA), by use of several mouse mutants carrying either truncated, catalytically inactive enzymes or aggrecanase-resistant mutant aggrecan. We have selected recombinant monoclonal antibodies directed against ADAMTS5, by using Intracellular Antibody Capture Technology (IACT). CRB0017 revealed very high affinity for the enzyme in Biacore analyses and very good specificity in a panel of binding assays. Therefore, we tested CRB0017 in a relevant spontaneous OA model, the STR/ort mouse. DESIGN: STR/ort male mice were recruited at 5 months of age, and treated intra-articularly in each knee with CRB0017 1.2 µg, CRB0017 12 µg, or vehicle. After 6 weeks, the intra-articular administration of CRB0017 was repeated with the same doses. After 3 months from recruitment, the animals were sacrificed and the femorotibial joints processed for histology and scored in a blind fashion according to both Mankin's and the OARSI methods. RESULTS AND CONCLUSIONS: All histological scores were significantly decreased in the CRB0017 12 µg/knee group compared to vehicle, while administration of CRB0017 1.2 µg was associated with a trend to a decrease in the same parameters. Therefore, CRB0017 administered twice in 3 months could modify the course of OA in the STR/ort mouse, by delaying cartilage breakdown as assessed histologically. The procedure of blind scoring of the histological samples clearly showed that knee intra-articular administration of CRB0017, an anti-ADAMTS5 antibody, dose-dependently improved disease progression in a relevant animal model of OA.
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Proteínas ADAM/antagonistas & inhibidores , Anticuerpos Monoclonales/uso terapéutico , Artritis Experimental/prevención & control , Osteoartritis/prevención & control , Proteínas ADAM/inmunología , Proteína ADAMTS5 , Animales , Anticuerpos Monoclonales/administración & dosificación , Artritis Experimental/patología , Progresión de la Enfermedad , Esquema de Medicación , Evaluación Preclínica de Medicamentos/métodos , Inyecciones Intraarticulares , Masculino , Ratones , Ratones Endogámicos , Osteoartritis/patología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéuticoRESUMEN
The new research survey "Okkio alla salute", conducted in children in the 3rd year of elementary school, has confermed the worrisome phenomenon of the high number of obese and overweight children. Therefore, it is necessary, also in light of the few available resources, to fight back against this phenomenon that has been demonstrated to be a cause of disabling illnesses in adults. There must therefore be collaboration between Departments of Prevention and Hygiene and Nutrition services (SIAN) to build valid and efficient pathways. In this presentation we describe some national projects carried out by various local health agencies to address this health problem.
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Conducta Alimentaria , Obesidad/prevención & control , Sobrepeso/prevención & control , HumanosRESUMEN
Cross-Reacting Material 197 (CRM197) is a diphtheria toxin non-toxic mutant that has shown antitumor activity in mice and humans. It is still unclear whether this anti-tumorigenic effect depends on its strong inflammatory-immunological property, its ability to inhibit heparin-binding epidermal growth factor (HB-EGF), or even its possible weak toxicity. CRM197 is utilized as a specific inhibitor of HB-EGF that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. In this study we evaluate the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible influence on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment (MTT modified assay), or changes in cell cycle distribution (flow cytometry), in EGFR localization, phospho-EGFR detected signals (immunohistochemistry) or in morphology (scanning electron microscopy, SEM) they show a change in the gene expression profile by microarray analysis (cDNA microarray SS-H19k8). The overexpression of genes like protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA), guanine nucleotide-binding protein G subunit alpha-1(GNAI1) and butyrophilin, subfamily 2, member A1 (BTN2A1) has been confirmed with real-time-qPCR. This is the first study where the CRM197 treatment on HT-29 shows a possible scarce implication of endogenous HB-EGF on EGFR expression and cancer cell development. At the same time, our results show the alteration of a specific and selected number of genes.
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Proteínas Bacterianas/farmacología , Neoplasias del Colon/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colorantes , ADN Complementario/biosíntesis , ADN Complementario/genética , Enterocitos/efectos de los fármacos , Enterocitos/metabolismo , Receptores ErbB/biosíntesis , Receptores ErbB/genética , Citometría de Flujo , Células HT29 , Factor de Crecimiento Similar a EGF de Unión a Heparina , Humanos , Inmunohistoquímica , Hibridación in Situ , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Análisis por Micromatrices , Microscopía Electrónica de Rastreo , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Receptor ErbB-4 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Azul de TripanoRESUMEN
Effectiveness comparison of different school-based nutrition education interventions to improve fruit and vegetable (F&V) consumption in schoolchildren not yet well researched. We evaluated the effectiveness of two school-based interventions promoting fruit and vegetable intake among Italian schoolchildren. In this randomized intervention trials, the first intervention was conducted by schoolteachers who attended a nutritionist-led training course (group-1), the second intervention conducted by schoolteachers who performed a self-training course (group-2). Thirty-two second to fifth-grade elementary classes enrolling 96 schoolteachers and 813 schoolchildren were randomized, and assigned to the two different nutrition education interventions. 804 students completed the study. By the end of the study, the group-1 (n = 409) followed by the teachers who attended a nutritionist-led course successfully increased the consumption of fruit and vegetables: in 183 (44.7%) and 157 (38.3%) schoolchildren respectively; the group-2 (n = 395) with teachers who performed a self-training course reported an increased consumption of fruit and vegetables in 81 (20.5%) and 76 (19.2%), respectively. This study indicates that a school-based nutrition education conducted by teachers who attended a nutritionist-led training course has a significant impact on primary school-age children's F&V intake.
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Ciencias de la Nutrición del Niño/educación , Dieta/tendencias , Docentes , Frutas , Educación en Salud , Verduras , Algoritmos , Niño , Análisis por Conglomerados , Curriculum , Femenino , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud , Humanos , Italia , Masculino , Instituciones Académicas , EnseñanzaRESUMEN
A short-version (15-week long) of school-based nutrition education program called "Bring Fruit to School" to enhance primary schoolchildren's fruit and vegetable (F&V) intake was evaluated. We recruited 199 primary schoolchildren from 8 classes (grade 2-5). The primary end-point was an increase in the children's F&V intake. The intervention period lasted 15 weeks, and was divided into three phases: weeks 1-5, weeks 6-10 and weeks 11-15. The F&V intake of the schoolchildren was also monitored in a subsequent follow-up period (16th-32nd week). By week 15, 92 (46.2%, P < .001) schoolchildren increase fruit intake and 91 (45.7%, P < .001) increase vegetable intake. The F&V intake increased during the intervention period and was constant in follow-up. The BFtS program is an effective means to promote primary schoolchildren's F&V intake, and was implemented in Italy by the Food and Nutrition Service of Foggia's Local Health Authority. It could be extended to many other countries by local nutrition agencies, such as associations for nutrition.
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Dieta , Frutas , Educación en Salud , Política Nutricional , Verduras , Niño , Humanos , Italia , Factores de TiempoRESUMEN
BACKGROUND: Acute pouchitis, an idiopathic inflammatory condition of the ileal pouch anal anastomosis, is the most frequent complication after proctocolectomy for ulcerative colitis. AIM: To test the hypothesis that sulfasalazine (SASP) might have a synergistic beneficial effect in acute pouchitis, by combining the anti-inflammatory activity of 5-aminosalicylic Acid and the bacteriostatic effect of sulphapyridine. METHODS: Twenty two patients were investigated for acute pouchitis; the Pouchitis Disease Activity Index (PDAI) was calculated and 11 patients with acute pouchitis (PDAI >7) were included in an open study, after obtaining their informed consent. Patients were treated with SASP 500 mg tablets, two tablets three times per day (3000 mg daily), for 2 months. Pouch endoscopy with biopsies was performed at the entry and at the end of the study. RESULTS: According to the PDAI score, 8/11 patients (73%) improved their clinical condition and 7/11 (63%) were in remission at the end of the treatment. At 8 weeks, the median PDAI index decreased from 11.2 +/- 2.3 to 6.6 +/- 4.7 P < 0.01. No adverse events or toxicity were reported and all patients completed the study. CONCLUSIONS: Despite the limitations of the current study, sulfasalazine seems to be a potential treatment for acute pouchitis.
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Reservorios Cólicos/patología , Mucosa Intestinal/patología , Mesalamina/uso terapéutico , Reservoritis/tratamiento farmacológico , Proctocolectomía Restauradora/efectos adversos , Sulfasalazina/uso terapéutico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Reservoritis/etiología , Reservoritis/patología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
The many nutrition education guidelines formulated by different organizations and institutions are the frames for the program actions targeting nutrition awareness in the school-age population. But while the guidelines represent a solid starting block they still need to be backed up by programs giving concrete form to the guiding principles, a program whose efficacy is demonstrated by specific applications studies. The aim of the "Bring Fruit at School" nutrition education program is to encourage elementary school children to change their eating habits for the better. And in particular to eat more fruit, vegetables, legumes, and fish and to cut down on junk-food and sugar-sweetened drink.
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Conducta Alimentaria , Frutas , Promoción de la Salud/métodos , Niño , Humanos , Desarrollo de Programa , Instituciones AcadémicasRESUMEN
AIM: Analysing the effectiveness of a surgical procedure is mandatory in every modern health-care system. The aging of the population stresses the need for a good standard of care. This study tests the hypothesis that porthsmouth-physiologic operative severity score for enumeration of morbidity and mortality (P-POSSUM) and colorectal-POSSUM (CR-POSSUM) would be useful clinical auditing tools in colorectal cancer surgery for aged patients. METHOD: One hundred and seventy-seven consecutive patients over 70 years of age underwent emergency or elective surgery from January 2003 to December 2005. Demographic, clinical and surgical information, score systems' prediction, complications and 30-day mortality data were prospectively entered in a comprehensive database. The observed over expected morbidity and mortality rate was calculated. RESULTS: Thirty-day observed mortality was 10.3% (19/177) while P-POSSUM and CR-POSSUM expected mortality were, respectively, 11.21% (P = NS) and 13.08% (P = NS). Overall observed morbidity was 42.7%, P-POSSUM prediction was 59.3% (P = 0.002). Morbidity and mortality data were analysed for specific subgroups of patients (resection and anastomosis/resection and stoma/palliative; emergency/elective). CONCLUSION: P-POSSUM and CR-POSSUM are useful tools to predict mortality in elderly patients. P-POSSUM significantly overestimated the risk of complications. A more accurate tool for preoperative assessment for aged patients is probably needed to predict the post-surgical outcome.
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Colectomía/mortalidad , Neoplasias del Colon/cirugía , Colostomía/mortalidad , Neoplasias del Recto/cirugía , Índice de Severidad de la Enfermedad , Anciano , Anciano de 80 o más Años , Colectomía/efectos adversos , Colostomía/efectos adversos , Humanos , Italia/epidemiología , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
In neurosciences, rabies virus (CVS strain) has become a very powerful tool for studying multisynaptic neuronal connections, due to its ability to function as a self-replicating marker and to propagate exclusively between connected neurons by transneuronal transfer, which is strictly time-dependent. In this laboratory, transneuronal tracing studies of rabies virus propagation in primates and rodent models during the asymptomatic period have provided valuable information on rabies pathogenesis. We have shown that rabies virus propagates by fast axonal transport at similar speeds in primates and rodents, after inoculation into the peripheral or central nervous system (CNS). Intracellulartransport of rabies virus is preferentially addressed to neuronal dendrites rather than axons, since transneuronal transfer occurs only retrogradely, i.e., from dendrites of first infected neurons to presynaptic terminals of connected neurons. Rabies virus propagation occurs at chemical synapses, but not via gap junctions or local spread. The results of our studies show that rabies virus receptors have a ubiquitous distribution on neurons within the CNS. Conversely, in the peripheral nervous system, rabies virus receptors are present only on motor endings, since uptake is restricted to motor endplates and axons, whereas sensory and autonomic endings are not infected. Thus, after peripheral inoculations, motoneurons are the only gateway for rabies virus transmission to the CNS. Infection of sensory and autonomic neurons requires longer incubation times, since it reflects centrifugal propagation of rabies virus from the CNS to the periphery, i.e., it is the result of retrograde transneuronal transfer to sensory and autonomic terminals within the CNS.
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Red Nerviosa/citología , Vías Nerviosas/citología , Neuronas/virología , Virus de la Rabia/fisiología , Rabia/patología , Animales , Transporte Axonal/fisiología , Encéfalo/citología , Encéfalo/virología , Modelos Animales de Enfermedad , Cobayas , Cinética , Macaca , Red Nerviosa/fisiología , Red Nerviosa/virología , Vías Nerviosas/fisiología , Vías Nerviosas/virología , Rabia/virología , Ratas , Sensibilidad y EspecificidadRESUMEN
Sarcomatoid carcinoma is a rare form of primitive carcinoma of the small bowel; it is considered a variant of adenocarcinoma, histologically characterized by a typical biphasic pattern with epithelial- and mesenchymal-like cells. Twenty-one cases have been described in the literature, presenting as small bowel obstructions (twenty cases) or superior vena cava syndrome (one case). The authors report the case of a 56 year-old man on immunosuppressive therapy for a heart transplant, who underwent surgery after a history of repeated episodes of melena, anemization and bowel obstruction. The operation brought to light an intraluminal occlusive mass in the distal ileum, associated with other intraluminal neoplasms of different sizes throughout the small bowel. No evidence of mesenteric adenopathies or hepatic metastases were found. Histological examination and immunohistochemical stain showed an anaplastic sarcomatoid carcinoma. The tumor cells showed strong positivity for cytokeratin and vimentin, and negativity for CD117 and CD34, as well as for all other characteristic markers of mesenchymal tumors. Early diagnosis is usually very difficult, due to the lack of any stereotyped clinical expression and the difficult to study the small bowel. Small-bowel barium follow-through or video capsule endoscopy can be helpful. In most cases, an emergency surgical operation is performed without a clear preoperative diagnosis. The case report is completed by a review of the literature.
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Carcinoma , Trasplante de Corazón , Neoplasias del Íleon , Carcinoma/etiología , Carcinoma/patología , Carcinoma/cirugía , Humanos , Neoplasias del Íleon/etiología , Neoplasias del Íleon/patología , Neoplasias del Íleon/cirugía , Terapia de Inmunosupresión/efectos adversos , Masculino , Persona de Mediana EdadRESUMEN
Fitz-Hugh-Curtis is a rare syndrome characterised by perihepatitis following pelvic inflammatory disease. We report the case of a patient with a right ovarian teratoma, abnormal liver tests and pain in the right abdomen and shoulder, initially attributed to an acalculous cholecystitis. Before gynaecological surgery, a repeat ultrasound scan found several small avascular peritoneal masses at the upper dome of the liver, not reported in the initial examination. This prompted laparoscopic exploration of the subdiaphragmatic space, and the final diagnosis of Fitz-Hugh-Curtis-syndrome was made. Such ultrasound finding appears to be a new diagnostic feature of this syndrome.
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Colecistitis Aguda/diagnóstico , Hepatitis/diagnóstico , Neoplasias Ováricas/diagnóstico por imagen , Enfermedad Inflamatoria Pélvica/diagnóstico , Teratoma/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Ováricas/cirugía , Síndrome , Teratoma/cirugía , UltrasonografíaRESUMEN
We used the [14C]-2-deoxyglucose method to study the location and extent of primate frontal lobe areas activated for saccades and fixation and the retrograde transneuronal transfer of rabies virus to determine whether these regions are oligosynaptically connected with extraocular motoneurons. Fixation-related increases of local cerebral glucose utilization (LCGU) values were found around the fundus of the inferior limb of the arcuate sulcus (AS) just ventral to its genu, in the dorsomedial frontal cortex (DMFC), cingulate cortex, and orbitofrontal cortex. Significant increases of LCGU values were found in and around both banks of the AS, DMFC, and caudal principal, cingulate, and orbitofrontal cortices of monkeys executing visually guided saccades. All of these areas are oligosynaptically connected to extraocular motoneurons, as shown by the presence of retrogradely transneuronally labeled cells after injection of rabies virus in the lateral rectus muscle. Our data demonstrate that the arcuate oculomotor cortex occupies a region considerably larger than the classic, electrical stimulation-defined, frontal eye field. Besides a large part of the anterior bank of the AS, it includes the caudal prearcuate convexity and part of the premotor cortex in the posterior bank of the AS. They also demonstrate that the oculomotor DMFC occupies a small area straddling the ridge of the brain medial to the superior ramus of the AS. Our results support the notion that a network of several interconnected frontal lobe regions is activated during rapid, visually guided eye movements and that their output is conveyed in parallel to subcortical structures projecting to extraocular motoneurons.
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Desoxiglucosa/metabolismo , Fijación Ocular/fisiología , Lóbulo Frontal/fisiología , Vías Nerviosas/fisiología , Virus de la Rabia , Movimientos Sacádicos/fisiología , Animales , Femenino , Lóbulo Frontal/anatomía & histología , Lóbulo Frontal/metabolismo , Macaca fascicularis , Macaca mulatta , Neuronas Motoras/fisiología , Músculos Oculomotores/inervaciónRESUMEN
BACKGROUND: The availability of drugs which can effectively inhibit gastric secretion allowed the control of the peptic disease in almost all the patients, but the incidence of complications is substantially unchanged. METHODS: In the present study, we performed a retrospective evaluation of 153 patients treated for complicated peptic ulcer (hemorrhage and perforation) in the last 6 years. Hemor-rhage is a common onset of the peptic disease and it rarely requires a surgical treatment, because medical and endoscopic therapies are successful in a high number of patients. RESULTS: Surgery was necessary in 17.2% of the cases in the group of patients studied. CONCLUSIONS: Our experience confirms the high operative mortality in the patients who underwent surgery for hemorrhage related to complicated peptic ulcer because of the frequent presence of several risk factors. Surgical therapy is the main procedure of treatment of perforated peptic ulcer and in the group of patient examined all the cases of perforation underwent surgical operation. In conclusion, despite the progress of pharmacological and endoscopic therapies, surgical treatment is the best therapy of complicated peptic ulcer.