Patient navigation (PN) support to timely access to radiotherapy in the Brazilian public health system.

PURPOSE: Patient navigation (PN) is a community-based service delivery intervention designed to promote access to timely diagnosis and treatment of cancer and other chronic diseases by eliminating barriers to integral care. Considering the complex difficulties in accessing treatment and the positive results of PN in high-income countries, our group decided to evaluate this tool to improve radiotherapy (RT) access in the public system in Brazil. PATIENTS AND METHODS: This pilot study took place in a public school hospital, with a historical cohort as the control arm. The primary endpoint was the time from histologic diagnosis and RT initiation among cancer patients receiving RT with curative intent in a PN program. The secondary objectives were the following time frames: referral to the first consultation by the RT team; first consultation up to RT beginning; RT beginning to RT end; referral to the end of RT and identifying/describing obstacles to the treatment; and assessing patient satisfaction with PN program. RESULTS: A total of 124 patients were included in the retrospective arm and 73 in the navigation arm. Most had the loco-regionally advanced disease from the esophagus, head/neck, and rectum. PN decreased the median time from the biopsy result to the beginning of RT from 108 to 74 days (p < 0.001). PN reduced the time between biopsy results and referral to RT (53 to 40.5 days, p = 0.011), between the referral and the first consultation in the RT (25 to 13 days, p < 0.001), and between the referral to the end of the RT (98 to 78 days, p < 0.003). CONCLUSIONS: Proper identification of barriers, especially in a low-resource setting, is mandatory to guide PN programs in LMICs. In an oncological context of socioeconomic vulnerability, PN is a financially viable and efficient tool to optimize access to timely RT.

The effects of volatile anesthetics on the extracellular accumulation of [(3)H]GABA in rat brain cortical slices.

GABA is an inhibitory neurotransmitter that appears to be associated with the action of volatile anesthetics. These anesthetics potentiate GABA-induced postsynaptic currents by synaptic GABAA receptors, although recent evidence suggests that these agents also significantly affect extrasynaptic GABA receptors. However, the effect of volatile anesthetics on the extracellular concentration of GABA in the central nervous system has not been fully established. In the present study, rat brain cortical slices loaded with [(3)H]GABA were used to investigate the effect of halothane and sevoflurane on the extracellular accumulation of this neurotransmitter. The accumulation of [(3)H]GABA was significantly increased by sevoflurane (0.058, 0.11, 0.23, 0.46, and 0.93 mM) and halothane (0.006, 0.012, 0.024, 0.048, 0072, and 0.096 mM) with an EC50 of 0.26 mM and 35 µM, respectively. TTX (blocker of voltage-dependent Na(+) channels), EGTA (an extracellular Ca(2+) chelator) and BAPTA-AM (an intracellular Ca(2+) chelator) did not interfere with the accumulation of [(3)H]GABA induced by 0.23 mM sevoflurane and 0.048 mM halothane. SKF 89976A, a GABA transporter type 1 (GAT-1) inhibitor, reduced the sevoflurane- and halothane-induced increase in the accumulation of GABA by 57 and 63 %, respectively. Incubation of brain cortical slices at low temperature (17 °C), a condition that inhibits GAT function and reduces GABA release through reverse transport, reduced the sevoflurane- and halothane-induced increase in the accumulation of [(3)H]GABA by 82 and 75 %, respectively, relative to that at normal temperature (37 °C). Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which is known to induce GABA release through reverse transport, abolished the sevoflurane and halothane effects on the accumulation of [(3)H]GABA. The effect of sevoflurane and halothane did not involve glial transporters because ß-alanine, a blocker of GAT-2 and GAT-3, did not inhibit the effect of the anesthetics. In conclusion, the present study suggests that sevoflurane and halothane increase the accumulation of GABA by inducing the reverse transport of this neurotransmitter. Therefore, volatile anesthetics could interfere with neuronal excitability by increasing the action of GABA on synaptic and extrasynaptic GABA receptors.

Challenging Outlook of Caring for Adolescents and Young Adults With Cancer in Brazil: Results of a Nationwide Survey.

PURPOSE: The global burden of cancer in adolescents and young adults (AYAs) emerges as a major public health issue, in which remarkable challenges and unmet needs are evident. Because of sociodemographic inequalities, initiatives to change this scenario need to be expanded globally, particularly to low-middle-income countries (LMICs). This study aimed to gain information about the standards of AYA cancer care in Brazil from the physician's perspective. METHODS: Physicians involved in AYA cancer care were invited to answer a national online survey. The questions covered several aspects from health care's demographics to specialized services availability, such as fertility and genetic counseling. The availability of a specialized AYA cancer care facility was the primary study end point, and the findings were stratified by region and treatment setting (public v private). RESULTS: Among the physicians who responded (N = 249), 90% reported no access to a specialized AYA service. Only 20% had access to a fertility specialist, and 30% to a survivorship program in their institutions. Even external referrals to medical specialties were challenging, with 24% of the physicians reporting challenges. Despite the potential cardiotoxicity related to treatments, 43% of the respondents reported to refer patients for cardio-oncologists hardly ever. Furthermore, 36% of physicians had never enrolled AYA patients into clinical trials and 42% had never ordered a genetic test. Lack of specialized human resources was particularly evident in Northern Brazil, and delays in cancer diagnoses were frequent. CONCLUSION: This first study addresses standards of AYA cancer care across Brazil. Importantly, the data disclose significant infrastructural gaps, implying that major investments in training and infrastructure are urgently needed. These data may mirror other LMICs reality.

Expression of MAPK and PI3K/AKT/mTOR Proteins according to the Chronic Liver Disease Etiology in Hepatocellular Carcinoma.

AIMS: Chronic liver disease (CLD) of different etiologies leads to hepatocellular carcinoma (HCC) by multiple mechanisms that may be translated into clinicopathological differences. We evaluated the tissue expression of the MAPK and PI3K/Akt/mTOR pathway proteins and their association with long-term outcome and other parameters, according to the etiology of the CLD, in HCC patients. METHODS: Clinicopathological data from 80 patients who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were compared according to CLD etiology. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analyzed. Pathway protein expression was assessed by immunohistochemistry (IHQ) in both tumor and underlying cirrhosis and by RT-PCR in tumor tissue. RESULTS: Strong expression (SE) of KRAS was more frequent in tumors arising from viral (26.8%) than the nonviral group of liver disease (7.7%, p=0.024) and also than cirrhotic parenchyma (0%, p=0.004). SE of PI3K was more frequent in tumor than in cirrhosis (p=0.048, p < 0.01), without differences in its tumor expression among etiologic groups (p=0.111). mRNA of ERK, PI3K, and BRAF was expressed in the tumor, without differences between CLD etiologies, and there was no association with IHQ findings. Older age and microvascular invasion (MIV) were the only parameters independently associated with the event. MIV was also associated with shorter EFS. CONCLUSIONS: Hepatitis B and C virus can lead to HCC by different mechanisms compared with nonviral hepatopathy. KRAS and PI3K may have a role in carcinogenesis. The prognostic and therapeutic implications need to be investigated.

The effect of sevoflurane on the release of [3H]dopamine from rat brain cortical slices.

Dopamine is a neurotransmitter that exerts major control on important brain functions and some lines of studies suggest that dopaminergic neurotransmission may be a potential target for volatile anesthetics. In the present study, rat brain cortical slices were labeled with [(3)H]dopamine to investigate the effects of sevoflurane on the release of this neurotransmitter. [(3)H]dopamine release was significantly increased in the presence of sevoflurane (0.46 mM) and this effect was independent of extracellular or intracellular calcium. In addition, [(3)H]dopamine release evoked by sevoflurane was not affected by TTX (blocker of voltage-dependent sodium channels) or reserpine (a blocker of the vesicular monoamine transporter). These data suggest that the dopamine release induced by sevoflurane is non-vesicular, independent of exocytosis and, would be mediated by the dopamine transporter (DAT). GBR12909 and nomifensine, inhibitors of DAT, decreased the release of [(3)H]dopamine evoked by sevoflurane. The same effect was also observed when the brain cortical slices were incubated at low temperature and low extracellular sodium. Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which is known to induce dopamine release through reverse transport, decreased [(3)H]dopamine release induced by sevoflurane. In conclusion, the present study suggests that sevoflurane increases [(3)H]dopamine release in brain cortical slices that is mediated by DAT located at the plasma membrane.

Halothane increases non-vesicular [(3)H]dopamine release from brain cortical slices.

Experimental data suggest that halothane anesthesia is associated with significant changes in dopamine (DA) concentration in some brain regions but the mechanism of this effect is not well known. Rat brain cortical slices were labeled with [(3)H]DA to further characterize the effects of halothane on the release of this neurotransmitter from the central nervous system. Halothane induced an increase on the release of [(3)H]DA that was dependent on incubation time and anesthetic concentration (0.012, 0.024, 0.048, 0.072 and 0.096 mM). This effect was independent of extracellular or intracellular calcium. In addition, [(3)H]DA release evoked by halothane was not affected by TTX (blocker of voltage-dependent Na(+) channels) or reserpine (a blocker of vesicular monoamine transporter). These data suggest that [(3)H]DA release induced by halothane is non-vesicular and would be mediated by the dopamine transporter (DAT) and norepinephrine transporter (NET). GBR 12909 and nomifensine, inhibitors of DAT, decreased the release of [(3)H]DA evoked by halothane. Nisoxetine, a blocker of NET, reduced the release of [(3)H]DA induced by halothane. In addition, GBR 12909, nisoxetine and, halothane decrease the uptake of [(3)H]DA into rat brain cortical slices. A decrease on halothane-induced release of [(3)H]DA was also observed when the brain cortical slices were incubated at low temperature and low extracellular sodium, which are known to interfere with the carrier-mediated release of the neurotransmitter. Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which induces DA release through reverse transport, decreased [(3)H]DA release induced by halothane. It is suggested that halothane increases [(3)H]DA release in brain cortical slices that is mediated by DAT and NET present in the plasma membrane.