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Exploiting the critical perioperative period to improve long-term cancer outcomes.

ABSTRACT: Evidence suggests that the perioperative period and the excision of the primary tumour can promote the development of metastases—the main cause of cancer-related mortality. This Review first presents the assertion that the perioperative timeframe is pivotal in determining long-term cancer outcomes, disproportionally to its short duration (days to weeks). We then analyse the various aspects of surgery, and their consequent paracrine and neuroendocrine responses, which could facilitate the metastatic process by directly affecting malignant tissues, and/or through indirect pathways, such as immunological perturbations. We address the influences of surgery-related anxiety and stress, nutritional status, anaesthetics and analgesics, hypothermia, blood transfusion, tissue damage, and levels of sex hormones, and point at some as probable deleterious factors. Through understanding these processes and reviewing empirical evidence, we provide suggestions for potential new perioperative approaches and interventions aimed at attenuating deleterious processes and ultimately improving treatment outcomes. Specifically, we highlight excess perioperative release of catecholamines and prostaglandins as key deleterious mediators of surgery, and we recommend blockade of these responses during the perioperative period, as well as other low-risk, low-cost interventions. The measures described in this Review could transform the perioperative timeframe from a prominent facilitator of metastatic progression, to a window of opportunity for arresting and/or eliminating residual disease, potentially improving long-term survival rates in patients with cancer.

SUBMITTER: Horowitz M

PROVIDER: S-EPMC5497123 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Exploiting the critical perioperative period to improve long-term cancer outcomes.

Horowitz Maya M Neeman Elad E Sharon Eran E Ben-Eliyahu Shamgar S

Nature reviews. Clinical oncology 20150120 4

Evidence suggests that the perioperative period and the excision of the primary tumour can promote the development of metastases—the main cause of cancer-related mortality. This Review first presents the assertion that the perioperative timeframe is pivotal in determining long-term cancer outcomes, disproportionally to its short duration (days to weeks). We then analyse the various aspects of surgery, and their consequent paracrine and neuroendocrine responses, which could facilitate the metasta ...[more]

PMID: 25601442

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Project description:BackgroundSpontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) exhibits dual intraoperative and postoperative advantages for patients with non-small cell lung cancer (NSCLC). However, there is a lack of data regarding its long-term survival superiority over the double-lumen intubated mechanical ventilation video-assisted thoracoscopic surgery (MV-VATS) or thoracotomy.MethodsA retrospective study was conducted from 2011 to 2018 in the First Affiliated Hospital of Guangzhou Medical University among patients with NSCLC who underwent the SV-VATS or the MV-VATS. Patients receiving the SV-VATS were the study group, and patients receiving the MV-VATS were the control group. Propensity score matching (PSM) was performed to establish 1:1 SV-VATS versus MV-VATS group matching to balance potential baseline confounding factors. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints were perioperative outcomes. The baseline information of these patients was recorded. The perioperative data and survival data were collected using a combination of electronic data record system and telephone interview. A 1:1:1 SPM was also used to compare the OS in the SV-VATS, the MV-VATS and thoracotomy group by using another database, including patients undergoing thoracotomy and the MV-VATS.ResultsFor the two-group comparison, after 1:1 PSM, a matched cohort with 400 (200:200) patients was generated. The median follow-up time in this cohort was 4.78 years (IQR, 3.78-6.62 years). The OS (HR =0.567, 95% CI, 0.330 to 0.974, P=0.0498) and the DFS (HR =0.546, 95% CI, 0.346 to 0.863, P=0.013) of the SV-VATS group were significantly better than the MV-VATS group. There were no statistically differences between the SV-VATS and the MV-VATS group on the operative time (158.56±40.09 vs. 172.06±61.75, P=0.200) anesthesia time (247.4±62.49 vs. 256.7±58.52, P=0.528), and intraoperative bleeding volume (78.88±80.25 vs. 109.932±180.86, P=0.092). For the three-group comparison, after 1:1:1 PSM, 582 (194:194:194) patients were included for the comparison of SV-VATS, MV-VATS and thoracotomy. The OS of the SV-VATS group was significantly better than the thoracotomy group (HR =0.379, 95% CI, 0.233 to 0.617, P<0.001).ConclusionsInvasive NSCLC patients undergoing SV-VATS lobectomy demonstrated better long-term outcomes compared with MV-VATS.

Project description:Study of the neural deficits caused by mismatched binocular vision in early childhood has predominantly focused on circuits in the primary visual cortex (V1). Recent evidence has revealed that neurons in mouse dorsolateral geniculate nucleus (dLGN) can undergo rapid ocular dominance plasticity following monocular deprivation (MD). It remains unclear, however, whether the long-lasting deficits attributed to MD during the critical period originate in the thalamus. Using in vivo two-photon Ca2+ imaging of dLGN afferents in superficial layers of V1 in female and male mice, we demonstrate that 14 d MD during the critical period leads to a chronic loss of binocular dLGN inputs while sparing response strength and spatial acuity. Importantly, MD leads to profoundly mismatched visual tuning properties in remaining binocular dLGN afferents. Furthermore, MD impairs binocular modulation, reducing facilitation of responses of both binocular and monocular dLGN inputs during binocular viewing. As predicted by our findings in thalamic inputs, Ca2+ imaging from V1 neurons revealed spared spatial acuity but impaired binocularity in L4 neurons. V1 L2/3 neurons in contrast displayed deficits in both binocularity and spatial acuity. Our data demonstrate that critical-period MD produces long-lasting disruptions in binocular integration beginning in early binocular circuits in dLGN, whereas spatial acuity deficits first arise from circuits further downstream in V1. Our findings indicate that the development of normal binocular vision and spatial acuity depend upon experience-dependent refinement of distinct stages in the mammalian visual system.SIGNIFICANCE STATEMENT Abnormal binocular vision and reduced acuity are hallmarks of amblyopia, a disorder that affects 2%-5% of the population. It is widely thought that the neural deficits underlying amblyopia begin in the circuits of primary visual cortex. Using in vivo two-photon calcium imaging of thalamocortical axons in mice, we show that depriving one eye of input during a critical period in development chronically impairs binocular integration in thalamic inputs to primary visual cortex. In contrast, visual acuity is spared in thalamic inputs. These findings shed new light on the role for developmental mechanisms in the thalamus in establishing binocular vision and may have critical implications for amblyopia.

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Exploiting the critical perioperative period to improve long-term cancer outcomes.

Publications

Exploiting the critical perioperative period to improve long-term cancer outcomes.

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