15 research outputs found
Histopathological growth patterns of colorectal liver metastasis exhibit little heterogeneity and can be determined with a high diagnostic accuracy
Colorectal liver metastases (CRLM) exhibit distinct histopathological growth patterns (HGPs) that are indicative of prognosis following surgical treatment. This study aims to assess the reliability and replicability of this histological biomarker. Within and between metastasis HGP concordance was analysed in patients who underwent surgery for CRLM. An independent cohort was used for external validation. Within metastasis concordance was assessed in CRLM with ≥ 2 tissue blocks. Similarly, concordance amongst multiple metastases was determined in patients with ≥ 2 resected CRLM. Diagnostic accuracy [expressed in area under the curve (AUC)] was compared by number of blocks and number of metastases scored. Interobserver agreement (Cohen’s k) compared to the gold standard was determined for a pathologist and a PhD candidate witho
Salvage treatment for recurrences after first resection of colorectal liver metastases: the impact of histopathological growth patterns
The majority of patients recur after resection of colorectal liver metastases (CRLM). Patients with CRLM displaying a desmoplastic histopathological growth pattern (dHGP) have a better prognosis and lower probability of recurrence than patients
with non-dHGP CRLM. The current study evaluates the impact of HGP type on the pattern and treatment of recurrences after
first resection of CRLM. A retrospective cohort study was performed, including patients with known HGP type after complete
resection of CRLM. All patients were treated between 2000 and 2015. The HGP was determined on the CRLM resected at
first partial hepatectomy. The prognostic value of HGPs, in terms of survival outcome, in the current patient cohort were
previously published. In total 690 patients were included, of which 492 (71%) developed recurrent disease. CRLM displaying
dHGP were observed in 103 patients (21%). Amongst patients with dHGP CRLM diagnosed with recurrent disease, more
liver-limited recurrences were seen (43% vs. 31%, p=0.030), whereas patients with non-dHGP more often recurred at multiple locations (34% vs. 19%, p=0.005). Patients with dHGP CRLM were more likely to undergo curatively intended local
treatment for recurrent disease (adjusted odds ratio: 2.37; 95% confidence interval (CI) [1.46–3.84]; p<0.001) compared
to patients with non-dHGP. The present study demonstrates that liver-limited disease recurrence after complete resection o
The Disease-Free Interval Between Resection of Primary Colorectal Malignancy and the Detection of Hepatic Metastases Predicts Disease Recurrence But Not Overall Survival
Introduction. The disease-free interval (DFI) between
resection of primary colorectal cancer (CRC) and diagnosis
of liver metastases is considered an important prognostic
indicator; however, recent analyses in metastatic CRC
found limited evidence to support this notion.
Objective. The current study aims to determine the
prognostic value of the DFI in patients with
resectable colorectal liver metastases (CRLM).
Methods. Patients undergoing first surgical treatment of
CRLM at three academic centers in The Netherlands were
eligible for inclusion. The DFI was defined as the time
between resection of CRC and detection of CRLM. Baseline characteristics and Kaplan–Meier survival estimates
were stratified by DFI. Cox regression analyses were performed for overall (OS) and disease-free survival (DFS),
with the DFI entered as a continuous measure using a
restricted cubic spline function with three knots.
Results. In total, 1374 patients were included. Patients
with a shorter DFI more often had lymph node involvement
of the primary, more frequently received neoadjuvant
chemotherapy for CRLM, and had higher number of
CRLM at diagnosis. The DFI significantly contributed to
DFS prediction (p =0.002), but not for predicting OS
(p =0.169). Point estimates of the hazard ratio (95% confidence interval) for a DFI of 0 versus 12 months and 0
versus 24 months were 1.284 (1.114–1.480) and 1.444
(1.180–1.766), respectively, for DFS, and 1.111
(0.928–1.330) and 1.202 (0.933–1.550), respectively, for
OS.
Conclusion. The DFI is of prognostic value for predicting
disease recurrence following surgical treatment of CRLM,
but not for predicting OS outcomes
Angiogenic desmoplastic histopathological growth pattern as a prognostic marker of good outcome in patients with colorectal liver metastases
Abstract
Background In patients with resectable colorectal liver metastases (CRLM), distinct histopathological growth patterns
(HGPs) develop at the interface between the tumour and surrounding tissue. The desmoplastic (d) HGP is characterised by
angiogenesis and a peripheral fibrotic rim, whereas non-angiogenic HGPs co-opt endogenous sinusoidal hepatic vasculature.
Evidence from previous studies has suggested that patients with dHGP in their CRLM have improved prognosis as compared
to patients with non-desmoplastic HGPs. However, these studies were relatively small and applied arbitrary cut-off values
for the determination of the predominant HGP. We have now investigated the
VÃnculos entre la polÃtica de incentivo a la demanda de tierra y vivienda e integración urbana en áreas de crecimiento urbano extensivo. El caso del PRO.CRE.AR en La Plata
Resumen La presente investigación tiene como propósito analizar el modo en que la polÃtica habitacional de incentivo a la demanda impulsada por PRO.CRE.AR incide en los procesos de expansión urbana, analizando los rasgos principales de la integración urbana: aspectos urbanos, ambientales y normativos. Los avances del trabajo permitieron reconocer que uno de los factores que tiene peso significativo es la localización del Programa en áreas no urbanas, como también en aquellas áreas que siendo urbanas, tienen grandes déficit de servicios y equipamientos públicos. Ello da cuenta de la dificultad que tiene el municipalidad para gestionar el acceso al suelo en condiciones urbanas de calidad, en una ciudad que se expande insustentablemente y donde el problema de la tierra es constante
B Cells as Prognostic Biomarker After Surgery for Colorectal Liver Metastases
Background: The aim of this study was to identify more accurate variables to
improve prognostication of individual patients with colorectal liver metastases (CRLM).
Clinicopathological characteristics only partly explain the large range in survival rates.
Methods: MessengerRNA expression profiles of resected CRLM of two patient groups
were analysed by mRNA sequencing: poor survivors (death from recurrent disease
60 months after
surgery). Tumour and adjacent liver parenchyma samples were analysed.
Results: MessengerRNA expression profiling of the tumour samples identified 77 genes
that were differentially expressed between the two survival groups at a False Discovery
Rate (FDR) <0.1. In the adjacent liver parenchyma samples only one gene, MTRNR2L1,
showed significantly higher expression in the good survivors. Pathway analysis showed
higher expression of immune-related and stroma-related genes in tumour samples from
good survivors. Expression data was then validated by immunohistochemistry in two
cohorts comprising a total of 125 patients. Immunohistochemical markers that showed to
be associated with good survival in the total cohort were: high K/L+ infiltration in tumour
stroma [p = 0.029; OR 2.500 (95% CI 1.100–5.682)] and high CD79A+ infiltration in
tumour stroma [p = 0.036; OR 2.428 (95%CI 1.062–5.552)].
Conclusions: A high stromal infiltration of CD79A+ B cells and K/L+ plasma cells might
be favourable prognostic biomarkers after surgery for CRLM
Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatment
Background: The aim of this study was to develop a prediction model for 10-year overall survival (OS) after resection of colorectal liver metastasis (CRLM) based on patient, tumour and treatment characteristics.Methods: Consecutive patients after complete resection of CRLM were included from two centres (1992-2019). A prediction model providing 10-year OS probabilities was developed using Cox regression analysis, including KRAS, BRAF and histopathological growth patterns. Discrimination and calibration were assessed using cross-validation. A web-based calculator was built to predict individual 10-year OS probabilities.Results: A total of 4112 patients were included. The estimated 10-year OS was 30% (95% CI 29 -32). Fifteen patient, tumour and treatment characteristics were independent prognostic factors for 10-year OS; age, gender, location and nodal status of the primary tumour, disease-free interval, number and diameter of CRLM, preoperative CEA, resection margin, extrahepatic disease, KRAS and BRAF mutation status, histopathological growth patterns, perioperative systemic chemotherapy and hepatic arterial infusion pump chemotherapy. The discrimination at 10-years was 0.73 for both centres. A simplified risk score identified four risk groups with a 10-year OS of 57%, 38%, 24%, and 12%.Conclusions: Ten-year OS after resection of CRLM is best predicted with a model including 15 patient, tumour, and treatment characteristics. The web-based calculator can be used to inform patients. This model serves as a benchmark to determine the prognostic value of novel biomarkers. (C) 2022 The Author(s). Published by Elsevier Ltd.Development and application of statistical models for medical scientific researc
The coagulation system in endocrine disorders: A narrative review
Endocrine disorders can influence the haemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. Also unprovoked bleeding or thrombotic events have been associated with endocrine disease. The aim of the present review is to summarise the available evidence on the influence of common endocrine disorders on the coagulation system, and their possible clinical implications. We focus on thyroid dysfunction, hyper- and hypocortisolism and growth hormone disturbances, while other endocrine disorders are only briefly discussed. In the published literature a clear bleeding diathesis has only been associated with overt hypothyroidism, mainly mediated by an acquired von Willebrand syndrome. A clinically relevant hypercoagulable state may be present in patients with hyperthyroidism, hypercortisolism or abnormal growth hormone levels, but adequate prospective clinical studies are lacking. Also effects of pheochromocytoma, hyperprolactinaemia and hyperaldosteronism on the coagulation system have been described. It is apparent that unprovoked bleeding and thrombotic episodes can be secondary to endocrine disorder