Background
Axillary lymph node status remains a significant prognostic indicator in breast cancer. Here, the diagnostic accuracy of ultrasound‐guided fine‐needle aspiration (US‐FNA) and ...ultrasound‐guided core needle biopsy (US‐CNB) in axillary staging was compared.
Methods
A comprehensive search was undertaken of all published studies comparing the diagnostic accuracy of US‐CNB and US‐FNA of axillary lymph nodes in breast cancer. Studies were included if raw data were available on the diagnostic performance of both US‐FNA and US‐CNB, and compared with final histology results. Relevant data were extracted from each study for systematic review. Meta‐analysis was performed using a random‐effects model. The pooled sensitivity and specificity of US‐FNA and US‐CNB were obtained using a bivariable model. Summary receiver operating characteristic (ROC) graphs were created to confirm diagnostic accuracy.
Results
Data on a total of 1353 patients from six studies met the inclusion criteria and were included in the final analysis. US‐CNB was superior to US‐FNA in diagnosing axillary nodal metastases: sensitivity 88 (95 per cent c.i. 84 to 91) versus 74 (70 to 78) per cent respectively. Both US‐CNB and US‐FNA had a high specificity of 100 per cent. Reported complication rates were significantly higher for US‐CNB compared with US‐FNA (7·1 versus 1·3 per cent; P < 0·001). Conversely, the requirement for repeat diagnostic procedures was significantly greater for US‐FNA (4·0 versus 0·5 per cent; P < 0·001).
Conclusion
US‐CNB is a superior diagnostic technique to US‐FNA for axillary staging in breast cancer.
Core needle biopsy better
Purpose
We aimed to compare the diagnostic accuracy of perioperative ΔcfDNA to ΔCEA (over the first 2 years post-operatively) for identifying disease recurrence in colon cancer.
Methods
Patients ...presenting for elective resection for colon cancer with curative intent were screened for inclusion. Perioperative cfDNA levels were measured at seven different times points(pre-operative and post-operative at 3 h, 6 h, 24 h, 48 h, POD3 and POD5). CEA levels were measured on the same patients up to 2 years post-operatively. Change in trend (
Δ
) was defined as the
β
coefficient using a logistic regression model. Statistical analysis was performed using SPSS, version 23.
Results
Longitudinal data on twenty-two patients were analysed (
n
= 16 male,
n
= 6 female) for a median of 29 months (IQR 23 months) during which time three patients developed (distant) recurrence. Perioperative ΔcfDNA at 48Hrs, POD3 and POD5 were significantly associated with early recurrence. ΔCEA was significantly associated with early recurrence at 6 months, 1 year and 2 years post-operatively, only when disease recurrence was macroscopically established. ΔcfDNA was associated with an area under the curve (AUC) of 0.947 (95% CI 0.88–1.0,
p
< 0.001) and ΔCEA was associated with an AUC of 0.9382 (95%CI 0.88–0.99,
p
< 0.0001). This translated into a specificity of 97% (95%CI 86.51–99.87%) for ΔcfDNA and 77.5% sensitivity (95%CI 62.5–87.7%) in the immediate perioperative period and an 88.9% specificity (95%CI 56.5–99.4%) and 76.5% sensitivity (95%CI 63.24–86%) for ΔCEA over the first 2 years post-operatively.
Conclusions
In this pilot study, following curative resection for colon cancer changing trends in perioperative cfDNA (ΔcfDNA) identify those at risk of recurrent disease before recurrence develops which is at least 6 months earlier than CEA changes (ΔCEA) which are only observed when recurrence is established.
Background
Carriers of the BRCA1 and/or BRCA2 mutation incur a lifetime risk of up to 85 per cent for breast cancer, and between 20 and 40 per cent for ovarian cancer. Efforts to estimate the ...lifetime risk of developing colorectal cancer for BRCA mutation carriers have produced conflicting results. Consequently, there are no formal guidelines regarding the need for bowel screening for individuals with BRCA1 and/or BRCA2 mutations. This systematic review and meta‐analysis determined the risk of colorectal cancer associated with BRCA carrier mutations.
Methods
The primary outcome was incidence of colorectal cancer in BRCA mutation carriers. Secondary outcomes were the incidence in BRCA1 and BRCA2 carriers, Ashkenazi Jews, and age‐ and sex‐matched cohorts.
Results
Eleven studies were included in the review, with an overall population of 14 252 and 4831 colorectal cancers identified. Nine studies were included in the meta‐analysis. There was no increase in colorectal cancer among patients carrying a BRCA mutation (odds ratio 1·03, 95 per cent c.i. 0·80 to 1·32; P = 0·82). After adjustment for Ashkenazi heritage, and age and sex estimates, there was no increased odds of developing colorectal cancer (with no heterogeneity, I2 = 0 per cent).
Conclusion
BRCA1 and/or BRCA2 mutation carriers are not at a higher risk of colorectal cancer.
Antecedentes
Las portadoras de la mutación BRCA1 y/o BRCA2 presentan un riesgo a lo largo de la vida de hasta un 85% para presentar un cáncer de mama y entre 20‐40% para el cáncer de ovario. Los esfuerzos para estimar el riesgo de desarrollar cáncer colorrectal (colorectal cancer, CCR) a lo largo de la vida en portadoras de mutaciones BRCA han dado resultados contradictorios. En consecuencia, no existen pautas formales con respecto a la necesidad de realizar el cribado de CRC en personas portadoras de mutaciones BRCA1 y/o BRCA2. Esta revisión sistemática y metaanálisis analiza el riesgo de CRC asociado en pacientes portadoras de mutaciones BRCA.
Métodos
Se incluyeron nueve estudios en el metaanálisis. La población general del estudio fue de 18.839 pacientes, con 4.978 con CRC identificado. La variable principal fue la incidencia de cáncer colorrectal en portadoras de mutaciones BRCA. Las variables secundarias incluyeron el análisis de la incidencia de subgrupos en BRCA 1, BRCA 2, etnia judía Ashkenazi y cohortes emparejadas por edad y sexo.
Resultados
No hubo un aumento de CRC en pacientes con una mutación BRCA (razón de oportunidades, odds ratio, OR 1,03; i.c. del 95% 0,80‐1,32; P = 0,82). Cuando se ajustó de acuerdo con la ascendencia Ashkenazi y las estimaciones de edad y sexo, no hubo mayores probabilidades de desarrollar cáncer colorrectal (sin heterogeneidad en los estudios (I2 = 0)).
Conclusión
Este metaanálisis concluye que el riesgo de cáncer colorrectal no fue significativamente mayor en las portadoras de mutaciones BRCA1 y/o BRCA2. Sin embargo, se requiere más evidencia antes de no recomendar la colonoscopia de cribado a las portadoras de la mutación BRCA1/2. Las pruebas de inmunoquímica fecal pueden ser una alternativa apropiada en esta población.
BRCA1 and/or BRCA2 mutation carriers incur a lifetime risk of up to 85 per cent for breast cancer, and between 20 and 40 per cent for ovarian cancer. The aim of this study was to clarify whether an association between BRCA mutation and colorectal cancer risk exists by conducting a systematic review and meta‐analysis of published peer‐reviewed studies. There was no significant increase in the odds of having colorectal cancer in patients carrying a BRCA mutation (odds ratio 1·03, 95 per cent c.i. 0·80 to 1·32; P = 0·82).
No increased risk
Aim
Laparoscopic colon and rectal cancer surgery is oncologically equivalent to open resection, but the impact of conversion is undetermined. The aim of this study was to assess the oncological ...outcome and predictive factors associated with conversion.
Method
A comprehensive search for published studies examining the associated factors and outcome of conversion from laparoscopic to open colorectal cancer resection was performed adhering to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta‐analyses) guidelines. Only randomized control trials and prospective studies were included. Each study was reviewed and the data extracted. Random effects methods were used to combine data.
Results
Fifteen studies, including 5293 patients, met the inclusion criteria. Of these 4391 patients had a completed laparoscopic resection and 902 were converted to an open resection. The average conversion rate of the studies was 17.9 ± 10.1%. Meta‐analysis showed completed laparoscopic surgery favoured lower 30‐day mortality (OR 0.134, 95% CI 0.047–0.385, P < 0.0001), lower long‐term disease recurrence (OR 0.634, 95% CI 0.421–0.701, P < 0.023) and lower overall mortality (OR 0.512, 95% CI 0.417–0.629, P < 0.0001). Factors negatively associated with completion of laparoscopic surgery were male gender (P = 0.011), rectal tumour (P = 0.017), T3/T4 tumour (P = 0.009) and node‐positive disease (P = 0.009). Completed laparoscopic surgery was also associated with a lower body mass index (BMI; mean difference −0.93 kg/m2, P = 0.004).
Conclusion
The results suggest that conversion from laparoscopic to open colorectal cancer resection is influenced by patient and tumour characteristics and is associated with an adverse perioperative outcome. Although confounding factors such as advanced tumour stage and elevated BMI are present, unsuccessful laparoscopic surgery appears to be associated with an adverse long‐term oncological outcome.
Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Of these, vascular endothelial growth factor, VEGF, is of particular interest because of its ...ability to induce neovascularization (angiogenesis). To determine whether VEGF is required for bone repair, we inhibited VEGF activity during secondary bone healing via a cartilage intermediate (endochondral ossification) and during direct bone repair (intramembranous ossification) in a novel mouse model. Treatment of mice with a soluble, neutralizing VEGF receptor decreased angiogenesis, bone formation, and callus mineralization in femoral fractures. Inhibition of VEGF also dramatically inhibited healing of a tibial cortical bone defect, consistent with our discovery of a direct autocrine role for VEGF in osteoblast differentiation. In separate experiments, exogenous VEGF enhanced blood vessel formation, ossification, and new bone (callus) maturation in mouse femur fractures, and promoted bony bridging of a rabbit radius segmental gap defect. Our results at specific time points during the course of healing underscore the role of VEGF in endochondral vs. intramembranous ossification, as well as skeletal development vs. bone repair. The responses to exogenous VEGF observed in two distinct model systems and species indicate that a slow-release formulation of VEGF, applied locally at the site of bone damage, may prove to be an effective therapy to promote human bone repair.
Excisional surgery is one of the primary treatment modalities for cancer. Minimal residual disease (MRD) is the occult neoplastic disease that remains in situ after curative surgery. There is ...increasing evidence that tumour removal alters the growth of MRD, leading to perioperative tumour growth. Because neoplasia is a systemic disease, this phenomenon may be relevant to all patients undergoing surgery for cancer. In this review we discuss the published work that addresses the effects of tumour removal on subsequent tumour growth and the mechanisms by which tumour excision may alter residual tumour growth. In addition, we describe therapeutic approaches that may protect patients against any oncologically adverse effects of tumour removal. On the basis of the evidence presented, we propose a novel therapeutic paradigm; that the postoperative period represents a window of opportunity during which the patient may be further protected against the oncological effects of tumour removal.
Posterior reversible encephalopathy syndrome (PRES) is a reversible leukoencephalopathy characterised by subcortical vasogenic oedema and neurological signs. We present the case of a 64-year-old ...woman who presented to hospital with symptomatic primary hyperparathyroidism. Her parathyroid hormone (PTH) level on admission was elevated at 1,330ng/l (normal range15-68ng/l) and her serum calcium measured 4.83mmol/l (normal range 2.25-2.54mmol/l). Technectium-99m sestamibi scan demonstrated a focus of radiotracer uptake consistent with a right upper parathyroid adenoma or carcinoma. After commencing appropriate medical treatment, the patient developed intractable seizures necessitating endotracheal intubation. Magnetic resonance imaging of her brain revealed bilateral symmetrical T2 hyperintensities in the posterior circulation consistent with PRES. Following stabilisation and further medical treatment for hypercalcaemia, the patient underwent a parathyroidectomy. Preoperative rapid PTH assay measured 1,021ng/l. Following excision, PTH levels fell to just 10ng/l. She was extubated in the intensive care unit on postoperative day 1 and made an uneventful recovery. At her 6-week follow-up appointment, all neurological symptoms had resolved. PRES is a rare neurological entity more often seen in the setting of hypertension, immunosuppression and renal failure. The development of new neurological manifestations in the setting of known risk factors should raise suspicion for the underlying diagnosis.
Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the ...transcription factor NF-
κ
B. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively.
In vitro
tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-
κ
B by the selective NF-
κ
B inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing
in vitro
tumour cell vitronectin adhesion and ECM invasion by >40% (
P
<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-
κ
B through TLR-4. TLR-4 and NF-
κ
B inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-
κ
B-dependent manner.
Background
Obesity is a well-established risk factor for acute pancreatitis. Increased visceral fat has been shown to exacerbate the pro-inflammatory milieu experienced by patients.
This study aimed ...to investigate the relationship between the severity of acute pancreatitis and abdominal fat distribution parameters measured on computed tomography (CT) scan.
Methods
Consecutive patients admitted to Cork University Hospital with acute pancreatitis between January 2005 and December 2010 were evaluated for inclusion in the study. An open source image analysis software (Osirix, v 3.9) was used to calculate individual abdominal fat distribution parameters from CT scans by segmentation of abdominal tissues.
Results
A total of 214 patients were admitted with pancreatitis between January 2005 and December 2010. Sixty-two of these patients underwent a CT scan and were thus eligible for inclusion. Visceral fat volume was the volumetric fat parameter that had the most significant association with severe acute pancreatitis (
P
= 0.003). There was a significant association between visceral fat volume and subsequent development of systemic complications of severe acute pancreatitis (
P
= 0.003). There was a strong association between mortality and visceral fat volume (
P
= 0.019). Multivariate regression analysis, adjusted for gender, did not identify any individual abdominal fat distribution index as an independent risk factor for severe acute pancreatitis.
Conclusions
Overall, estimation of abdominal fat distribution parameters from CT scans performed on patients with acute pancreatitis indicates a strong association between visceral fat, severe acute pancreatitis, and the subsequent development of systemic complications. These data suggest that visceral fat volume should be incorporated into future predictive scoring systems.
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