Australasian ACPGBI risk prediction model for 30-day mortality after colorectal cancer surgery.

BACKGROUND: Postoperative mortality after colorectal cancer surgery varies across hospitals and countries. The aim of this study was to test the Association of Coloproctologists of Great Britain and Ireland (ACPGBI) models as predictors of 30-day mortality in an Australian cohort. METHODS: Data from patients who underwent surgery in six hospitals between 1996 and 2015 (CRC data set) were reviewed to test ACPGBI models, and patients from 79 hospitals in the Bi-National Colorectal Cancer Audit between 2007 and 2016 (BCCA data set) were analysed to validate model performance. Recalibrated models based on ACPGBI risk models were developed, tested and validated on a data set of Australasian patients. RESULTS: Of 18 752 patients observed during the study, 6727 (CRC data set) and 3814 (BCCA data set) were analysed. The 30-day mortality rate was 1·1 and 3·5 per cent in the CRC and BCCA data sets respectively. Both the original and revised ACPGBI models overestimated 30-day mortality for the CRC data set (observed to expected (O/E) ratio 0·17 and 0·21 respectively). Their ability to correctly predict mortality risk was poor (P < 0·001, Hosmer-Lemeshow test); however, the area under the curve for both models was 0·88 (95 per cent c.i. 0·85 to 0·92) showing good discriminatory power to classify 30-day mortality. The recalibrated original model performed well for calibration and discrimination, whereas the recalibrated revised model performed well for discrimination but not for calibration. Risk prediction was good for both recalibrated models. On external validation using the BCCA data set, the recalibrated models underestimated mortality risk (O/E ratio 3·06 and 2·98 respectively), whereas both original and revised ACPGBI models overestimated the risk (O/E ratio 0·48 and 0·69). All models showed similar good discrimination. CONCLUSION: The original and revised ACPGBI models overpredicted risk of 30-day mortality. The new Australasian calibrated ACPGBI model needs to be tested further in clinical practice.

ANTECEDENTES: La mortalidad postoperatoria tras la cirugía del cancer colorrectal (colorectal cáncer, CRC) varía entre hospitales y países. El objetivo de este estudio era evaluar los modelos de la Asociación de Coloproctólogos de Gran Bretaña e Irlanda (Association of Coloproctologists of Great Britain and Ireland, ACPGBI) como predictores de mortalidad a los 30 días en una cohorte de pacientes de Australia. MÉTODOS: Se revisaron los datos de pacientes sometidos a cirugía en seis hospitales entre 1996-2015 (datos CRC) para evaluar los modelos ACPGBI, mientras que los datos recogidos en 79 hospitales en la auditoría bi-nacional de cáncer colorrectal (Bi-National Colorectal Cancer Audit) entre 2007-2016 (datos BCCA) se analizaron para validar el comportamiento del modelo. Se desarrollaron modelos recalibrados basados en los modelos de riesgo ACPGBI que fueron aplicados y validados en un conjunto de datos multi-institucionales de pacientes australianos. La mortalidad observada y estimada (tasa 0/E) a 30 días se calculó en los modelos ACPGBI original y revisados usando el test de Hosmer-Lemeshow y los análisis de la curva de las características operador-receptor (ROC) para evaluar la calibración y discriminación de los modelos. RESULTADOS: De un total de 18,752 pacientes observados durante el periodo de estudio, se analizaron 6.727 (datos CRC) y 3.814 (datos BCCA). La mortalidad en los pacientes del grupo de datos CRC fue del 1,1% y en los del grupo de datos BCCA del 3,5%. Para el grupo de datos CRC, los modelos ACPGBI sobreestimaron significativamente la mortalidad a los 30 días, tanto en el modelo original como en el modelo revisado (O/E 0,17 y 0,21). La capacidad de los modelos para predecir correctamente el riesgo de mortalidad también fue limitada (test de Hosmer-Lemeshow 23,1 y 22.9); sin embargo, el área bajo la curva ROC de ambos modelos fue de 0,88 (i.c. del 95% 0,85-0,92) con una buena capacidad discriminatoria para clasificar a los pacientes que fallecían durante los primeros 30 días tras la cirugía. El modelo original ACPGBI recalibrado presentó un buen comportamiento para la predicción de riesgo (tasa O/E 1,06), pero no fue así en el caso del modelo revisado ACPGBI recalibrado (tasa O/E 0,99). En la validación externa con los datos BCCA, los modelos recalibrados subestimaron el riesgo de mortalidad a los 30 días (tasa O/E 3,06 y 2,98), mientras que los modelos ACPGBI original y revisado sobreestimaron el riesgo (tasa O/E 0,48 y 0,69, respectivamente). Todos los modelos mostraron una buena discriminación en las curvas ROC. CONCLUSIÓN: Los modelos ACPGBI original y revisado sobreestimaron el riesgo de mortalidad a los 30 días. Se desarrolló un nuevo modelo, denominado modelo ACPGBI calibrado australiano o modelo ACACPGBI, cuya utilidad en la práctica clínica debe ser evaluada.

Surgical outcome after standard abdominoperineal resection: A 15-year cohort study from a single cancer centre.

BACKGROUND: Abdominoperineal resection (APR) is associated with a poorer oncological outcome than anterior resection. This may be due to higher rates of intra-operative perforation and circumferential resection margin involvement. The aim of this study was to audit our short and long-term results of abdominoperineal resection performed using conventional techniques and to compare this with other published series. MATERIALS AND METHODS: A retrospective review of all patients who had standard APR between January 2000 and December 2016 in a single institution, Cabrini Hospital, Melbourne, Australia. A total of 163 cases performed by nine different colorectal surgeons for primary rectal adenocarcinoma were identified, with their clinicopathological data analysed. RESULTS: Using standard APR, only six patients (3.7%) were found to have a positive circumferential resection margin (CRM). There were two cases of intra-operative perforation (1.2%). Local recurrence rate was 5.6% of patients, with distant recurrence found in 24.9%. Disease-free survival at five years was 73.1%. Five-year overall survival was 66.7%, 67.9% of all deaths were cancer-related. CONCLUSION: Short and long-term outcomes after standard APR in this study were comparable to previous published studies. The CRM rate of 3.7% compares favourably to published positive CRM rates for standard APR which ranged from 6 to 18%. Standard APR remains a viable technique for the treatment of rectal cancer. Patient selection and adequate training remain important factors.

Vitamin D metabolism and regulation in pediatric MSCs.

Vitamin D is crucial for mineral homeostasis and contributes to bone metabolism by inducing osteoblast differentiation of marrow stromal cells (MSCs). We recently reported that MSCs from adults demonstrate 1α-hydroxylase activity in vitro and express vitamin D-related genes; this raises a possible autocrine/paracrine role for D activation in pre-osteoblasts. In this studies, we tested the hypotheses that pediatric MSCs have 1α-hydroxylase activity and express vitamin D-related genes. With IRB approval, we isolated MSCs from discarded excess iliac marrow graft from 6 male and 6 female subjects (age 8-12 years) undergoing alveolar cleft repair. 1α-hydroxylation of substrate 25(OH)D3 was measured by ELISA for 1α,25(OH)2D. RT-PCR was used for gene expression. Pediatric MSCs showed a range of 1α-hydroxylase activity in vitro. There was constitutive expression of vitamin D receptor (VDR), megalin, d-hydroxylases (CYP27B1, CYP27A1, CYP2R1, and CYP24A1), and estrogen receptor (ER). There was 2.6-fold greater expression of CYP27B1 and 3.5-fold greater expression of CYP24A1 in MSCs from boys compared with girls. There was 2.4-fold greater expression of ERα and 3.2-fold greater expression of megalin in MSCs from boys. In preliminary studies, treatment of female pediatric MSCs with 10nM 17ß-estradiol resulted in upregulation of CYP27B1 and CYP24A1, as well as VDR, megalin, ERα, and ERß. Treatment with 25(OH)D3 upregulated CYP27B1, VDR, and ERα. Expression and regulation of vitamin D related genes in pediatric hMSCs reinforces an autocrine/paracrine role for vitamin D in hMSCs. Finding striking gender differences in MSCs from children was not seen with MSCs from adults and adds insight to the metabolic environment of bone and presents a research approach for investigating and optimizing pediatric bone health.

[Systemic effects of intravenous dipyridamole in patients of various age groups]. / Effetti sistemici del dipiridamolo endovena in soggetti di diverse classi di età.

Aim of this study was to assess the role of age-related vascular response in the onset of i.v. dipyridamole effects. The results of 129 patients who underwent a dipyridamole infusion were reviewed. The patients were divided into three according to age: 47 patients of less than 50 years (group I), 54 patients aged between 50 and 60 years (group II) and 28 patients of more than 60 years (group III). For each group heart frequency (HF) and systolic blood pressure (SBP) were considered in basal conditions, at the end of infusion and at the minimum value of SBP (SBP min); moreover the time in reaching SBP min was considered (time to SBP min). At the end of the infusion no significant changes in SBP were observed in all groups while the SBP min value reached from group III were significantly lower than basal (142.6 +/- 20.4 mmHg, p less than 0.02). The HF, without significant differences among the three groups in basal conditions, increased significantly at the end of infusion only in group I and II, with a more significant increase in group I at the time of SBP min with respect to groups II and III. The group 3 showed moreover, a significant longer time to SBP min (286 +/- 208 sec) respect to the group I and II (145 +/- 130 and 160 +/- 177 sec respectively) (p less than 0.02). From these data it can resume that age could be a factor to determine hemodynamic response to intravenous dipyridamole.

[Relationship between arrhythmia profile, left ventricular function and sudden death in the post-infarct period of patients resuscitated from heart arrest]. / Relazione tra profilo aritmico, funzione ventricolare sinistra e morte improvvisa nel periodo post-infartuale di pazienti rianimati da un arresto cardiaco.

In order to determine the relationship among ventricular arrhythmias, left ventricular dysfunction and sudden cardiac death (SCD), 75 consecutive patients with myocardial infarction, 38 of whom resuscitated from SCD, were studied retrospectively by 48 hour Holter electrocardiographic monitoring (ECGD), cardiac catheterization and radionuclide angiography (ACRD). The patients were divided in 3 groups, related to SCD occurrence and to the interval between acute myocardial infarction (AMI) and SCD: Group I (37 patients-control group) no cardiac arrest occurred; Group II (26 patients) resuscitated less than or equal to 48 hours after AMI; Group III (12 patients) resuscitated 6-12 weeks after AMI. ECGDs were recorded with an average of 2 (ECGD 1), 16 (ECGD 2) and 36 months (ECGD 3) after AMI. In ECGD 1, there were no differences in the frequency and complexity of ventricular arrhythmias among the 3 groups, whereas in ECGD 2 and 3 the incidence of complex ventricular arrhythmias was significantly higher in Group III than in the other 2 groups (p less than 0.05). In Group III, the complexity and frequency of ventricular arrhythmias increased both in ECGD 2 and 3 compared to ECGD 1 (p less than 0.05). Furthermore, between patients of Group II and III higher grade arrhythmias and more frequent ventricular premature beats (VPB) were noted in sudden death patients than in survivors. There was no statistical difference in mean cardiac index, left ventricular end-diastolic pressure and ejection fraction among the groups. In the ACRD 1 performed an average of 8 months after AMI, a slight decrease of ejection fraction in Group III compared to the other groups was noted (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)