Five-year survival of resectable stage IIIA non-small cell lung cancer in Brazil.

BACKGROUND: In stage IIIA non-small cell lung cancer (NSCLC), surgery plays a role in terms of multimodal treatment. Surgery rates have increased in recent years, mainly due to the combination of more accurate imaging tools, electromagnetic navigation bronchoscopy, robotic bronchoscopy, robotic surgery, and a wide range of challenging clinical scenarios to lead surgeons and oncologists to include surgery as an option in therapeutic management. OBJECTIVES: To assess the prognostic factors, the 5-year overall survival (OS) and cancer-specific survival (CSS) of patients with resectable stage III-NSCLC. METHODS: Patients' information was extracted from 76 Hospitals' Cancer Registry. OS and CSS were constructed using the Kaplan-Meier method, and the log-rank test was used to assess differences between curves. In addition, Cox regression was conducted to evaluate the patients' characteristics leading to better OS and CSS. RESULTS: Overall, 433 stage III NSCLC surgical patients followed over 19 years were included. The median age was 61.29 ± 9.62 years, 58.4% male, 50.1% with adenocarcinoma, 29.3% with squamous cell carcinoma, 3.7% with large-cell lung carcinoma, and 16,9% with other lung cancer types. The 5-year OS was 30.6% (95% confidence interval [CI]: 27.4-36.1), and the CSS was 35.0% (95% CI: 29.4-41.0). In the Cox multivariate regression, squamous cell carcinoma was associated with reduced OS (hazard ratio [HR]: 1.40; 95% CI: 1.07-1.83; p=0.014) and CSS (HR: 1.56; 95% CI: 1.17-2.08; p = 0.002), in comparison with adenocarcinoma. The 2015-2019 quinquennial had a 50% reduction in HR (0.49; 95% CI: 0.29-0.81; p = 0.006), and the 2010-2014 group had a 40% reduction (0.59; 95% CI: 0.42-0.83; p = 0.006) in comparison with the 2000-2004 patients' group. CONCLUSION: The OS and CSS of patients with resectable stage III NSCLC have improved over the past 19 years in our region. Squamous cell carcinoma was associated with increased mortality risk from any cause or specific cancer.

Overall survival and prognostic factors in Stage I lung adenocarcinoma treated with curative intent: A real-life 19-year cohort study.

OBJECTIVES: Important differences in Stage I non-small-cell lung cancer (NSCLC) are related to the delay in the diagnosis to the treatment, hospitals' specialised status, comorbidities, tumour stage and histological type. METHODS: A 19-year retrospective cohort study was conducted, including 681 patients with NSCLC in clinical-stage IA-IB. The variables analysed were gender, age, schooling, type of health care provider, type of treatment, period of 5-year treatment, the time between first attendance to diagnosis and the time between diagnosis and treatment, and hospital's specialised status. RESULTS: Patients who underwent radiotherapy alone had three times more risk of death than those who underwent surgery alone (adjusted hazard ratio [adjHR] = 3.44; 95% confidence interval [CI]: 2.45-4.82; p <0.001). The independent risk of death factors was being treated in nonhigh complexity centres in oncology hospitals and having started the treatment more than 2 months after diagnosis (adjHR = 1.80; 95% CI: 1.26-2.56; p <0.001) and (adjHR = 2.00; 95% CI: 1.33-3.00; p <0.001), respectively. In addition, the patients diagnosed between 2011 and 2015 had a 40% lower risk of death when compared to those diagnosed between 2000 and 2005 (95% CI: 0.38-0.94; p = 0.027). CONCLUSION: The overall survival in curative intent Stage-I lung cancer patients' treatment was associated with the 5-year diagnosis group, the delayed time between diagnosis and treatment and the hospital qualification.

Efficacy and safety of a device used to prevent fogging and residue buildup on surgical optics during video-assisted thoracic surgical procedures (LacrimaSurg): a pilot in vivo study in 30 patients.

INTRODUCTION: Nowadays the majority of the surgical procedures are video surgeries. Despite technological advances, some problems remain. The buildup of residues in front of the lens is an example of this problem. To solve it, Abreu et al. (Surg Technol Int 26:43-47, 2015) developed LacrimaSurg, which works as a lacrimal duct in the optics preventing fogging and residues buildup on it. This had 98.1% of efficiency in an experimental study. OBJECTIVE: Study feasibility and safety of the device under real surgical conditions. MATERIALS AND METHODS: A pilot study included 30 patients undergoing thoracic procedures using LacrimaSurg. Procedures were recorded for further analysis by investigators. The characteristics of patients (age, sex, body mass index, Charlton comorbidity index), data of environment (Temperatures variances), and data of procedures (type of surgery and duration of it) were recorded. The investigators watched the videos and recorded the residue buildup and fogging events that impaired surgeon's vision. The number of times the optics got dirty, need for further jets of crystalloid solution, and need for mechanical cleaning were collected to evaluate efficacy. Comparative serum measurements of electrolytes before and after surgery were studied. Data were organized and analyzed by simple linear correlations and t test for continuous variables and Fisher's test for categorical variables. RESULTS: The use of the device allowed 97% of the procedures to be performed without interruption. No characteristics inherent to the patients or to the procedures that lead to fogging or filth of the optics were identified. There were no statistically significant differences between pre- and postoperative serum ions, and no postoperative complications related to the use of the device were observed. CONCLUSION: The device was effective in preventing interruption of surgical procedures due to dirt or fogging, its use was considered safe, and did not cause postoperative complications.

Real-Life Long-Term Cohort of Patients With Stage IIIA Non-Small-Cell Lung Cancer: Overall Survival Related to Patients' Characteristics and Multiple Treatment Models.

PURPOSE: This real-life cohort of patients describes the treatment patterns and compares the overall survival (OS) and hazard risk of utilization of multiple therapies. MATERIALS AND METHODS: Electronic medical registries of patients with stage III non-small-cell lung cancer (NSCLC) regularly attended in 72 hospitals were included. Univariate and multivariate analyses were conducted to evaluate the primary patients' characteristics leading to better OS and cancer-specific survival. RESULTS: A total of 3,363 patients with stage III NSCLC followed over 19 years were included in this study. The median age was 66.00 (58.00-72.00) years, 65% male, and 41.2% with squamous cell carcinoma followed by adenocarcinoma (34.6%) and undifferentiated carcinoma (13.1%) in clinical stage T3 (50.3%), T2 (29.3%), and T4 (12.3%). The median survival (in months) was 18.4 (95% CI, 16.9 to 19.5) in patients submitted to radiotherapy plus chemotherapy, 11.2 (95% CI, 10.5 to 12.1) to chemotherapy, 31.5 (95% CI, 25.9 to 37.7) to surgery plus chemotherapy, and 33.8 (95% CI, 28.3 to 47.8) to chemotherapy plus radiotherapy plus surgery. The median cancer-specific survival (in months) was 19.3 (95% CI, 17.9 to 20.9) in patients submitted to radiotherapy plus chemotherapy, 12.1 (95% CI, 11.1 to 12.9) to chemotherapy, 36.9 (95% CI, 29.6 to 43.2) to surgery plus chemotherapy, and 41.3 (95% CI, 32.1 to 61.3) to chemotherapy plus radiotherapy plus surgery. The patients treated with multiple chemotherapy plus radiotherapy followed by surgery had significantly better OS and lower mortality rates than those treated with other treatments (adjusted hazard ratio, 0.55; 95% CI, 0.45 to 0.66; P < .001). At the end of the study, 11.2% and 10.7% of the patients were living with and without cancer, respectively. CONCLUSION: Our real-life 19-year cohort study has shown that only 30.3% of the total patients with stage III NSCLC have been submitted to standard chemotherapy and radiotherapy treatment. This may show a substantial difference between the recruited clinical trials' patients and the real-life patients' characteristics in daily routine treatment.

Prognostic factors and patients' profile in treated stage I and II lung adenocarcinoma: a Hospital's Cancer Registry-based analysis.

BACKGROUND: It is known that survival from lung cancer can differ between countries and even between different regions of the same country. The variability between hospitals, the age and social profile, and the time when this patient was treated, can influence survival, and these factors are intrinsic to each region. Knowing the profile of patients, hospitals, and other factors associated with the treatment of stage I and II lung cancer in a given region is important to understand outcomes and propose improvements that can be replicated in any region of the world that presents the same profile of patients and care structure. This study evaluates survival and possible predictors in all patients with stage I and II lung cancer adenocarcinoma through the Hospital's Cancer Registry (HCR), responsible for the State of Sao Paulo's cancer registry, a geographical area with 40 million inhabitants. METHODS: Based on the HCR, an observational study was conducted, including 1,278 patients diagnosed with lung adenocarcinoma at clinical stages (CS) I and II. Sex, age at diagnosis, education, neighbourhood, CS at diagnosis, the time between diagnosis and treatment, 5-year periods in which patients were treated, treatment modality and hospitals where patients were treated were analysed. Cox univariate and multiple regression analyses were used to estimate the hazard ratio (HR). RESULTS: A total of 1,278 lung cancer patients with clinical lung cancer adenocarcinoma stages I and II were included. About 40.06% of patients did not receive surgery, and only 55.8% started the treatment within 2 months. The majority of the patients were treated in high complexity hospitals, 69%. Five-year overall survival (OS) was 45.6% in CS I and 27.5% in CS II. Patients treated in high complexity centres have lower mortality rates than those treated in Partial Hospital Complexity Centers in Oncology (PHCCO) (adjHR 1.18; 95% CI: 1.00-1.40; P=0.047). Patients diagnosed between 2010-2014 had a protective factor against the risk of death concerning patients diagnosed between 2000-2004. CONCLUSIONS: The 5-year OS has significantly improved as long as the 5-year group analysed. Also, the 5-year OS of the patients treated in high complexity hospitals is higher than those treated in PHCCO.

Gastric neuroendocrine tumor: A practical literature review.

Gastric neuroendocrine tumors are gastric neoplasms originating from enterochromaffin type cells and are inserted in a larger group, named gastroenteropancreatic neuroendocrine tumors. They are considered rare and variable in terms of their clinical, morphological and functional characteristics and may be indolent or aggressive. They are classified into types I, II and III, according to their pathophysiology, behavior and treatment. Their diagnosis occurs, in most cases, incidentally during upper digestive endoscopies, presenting as simple gastric polyps. Most cases (type I and type II) are related to hypergastrinemia, can be multiple and are treated by endoscopic resection, whenever possible. The use of somatostatin analogs for tumor control may be one of the options for therapy, in addition to total or subtotal gastrectomy for selected cases. Adjuvant chemotherapy is only reserved for poorly differentiated neuroendocrine carcinomas. Although rare, gastric neuroendocrine tumors have an increasing incidence over the years, therefore deserving more comprehensive studies on its adequate treatment. The present study reviews and updates management recommendations for gastric neuroendocrine tumors.

Susceptibility of virulent and resistant Escherichia coli strains to non-polar and polar compounds identified in Microplumeria anomala.

BACKGROUND AND AIM: Escherichia coli is one of the main pathogens responsible for veterinary and human infections, and it is associated with significant economic losses in the livestock, as it causes severe diseases to humans, particularly in children. For that reason, there is a need for introducing new drugs to treat E. coli diseases. The Brazilian species richness is a source of potential new antibacterial natural products. The study aimed at the biological and chemical investigation of the organic extract obtained from the stem of Microplumeria anomala (Apocynaceae), EB127, as it was identified as a potential source of new antibacterial compounds to be used in Veterinary. MATERIALS AND METHODS: The antibacterial activity was evaluated by disk diffusion and microdilution assays; chromatography, nuclear magnetic resonance spectrometry, and mass spectrometry were used in the isolation and identification of compounds. RESULTS: EB127 showed activity against E. coli ATCC25922, and against three E. coli strains that were isolated from frigarte's cloaca, named 31/1A, 35A, and 51A. Lupeol, 3-acetyl-11-oxo-ß-amyrin, 3-acetyl-11-oxo-α-amyrin, sitosterol, stigmasterol, 3ß,7α-dihydroxy-cholest-5-ene, 3ß-hydroxy-cholest-5-en-7-one, and 3ß-hydroxy-cholest-5,22-dien-7-one were identified in fraction Hex/CHCl3, while loganin, loganic acid, methylanomaline, and anomaline were all identified in EB127 and protocatechuic acid hexoside, ferulic acid, secoxyloganin, feruloylquinic acid, vanillic acid hexoside, protocatechuic acid-4-O-ß-hexoside, and rosmarinic acid were tentatively identified in fraction 10%ACN/H2O. E. coli 51A (virulent/non-resistant) showed sensitivity to the antibacterial action of fraction Hex/CHCl3 which contains alkaloids, triterpenes, and steroids, while E. coli 35A (resistant/non-virulent) were more susceptible to 10%ACN/H2O, which contains iridoids as loganin and loganic acid, and glycosylated and non-glycosylated caffeic acids. CONCLUSION: Fraction 10%ACN/H2O is of interest in pursuing new drugs to treat resistant E. coli, in veterinary. All compounds were isolated from the plant for the first time and have shown potential as new antibacterial natural products from Amazon plants to be used in veterinary and human diseases.

Prognostic factors of recurrence of malignant pleural effusion: what is the role of neoplasia progression?

BACKGROUND: It is known that malignant pleural effusion (MPE) recurs rapidly, in a considerable number of patients. However, some patients do not have MPE recurrence. Since MPE is associated with an average survival of 4-7 months, accurate prediction of prognosis may help recognize patients at higher risk of pleural recurrence, aiming to individualize more intensive treatment strategies. METHODS: A prospectively assembled database of cases with pleural effusion treated at a single institution analyzed a subset of patients with symptomatic MPE. Prognostic factors for pleural recurrence were identified by univariable analysis using Kaplan-Meier method and the log-rank test was used for the comparison between the curves. Univariate and multiple Cox regression models were used to evaluate the risk (HR) of recurrence. Receiver operating characteristics (ROC) analysis determined the cutoff points for continuous variables. RESULTS: A total of 288 patients were included in the analysis. Recurrence-free survival was of 76.6% at 6 months and 73.3% at 12 months. Univariable analysis regarding factors affecting postoperative recurrence was: lymphocytes, platelets, pleural procedure, chemotherapy lines and number of metastases. The independent factors for recurrence-free survival were pleural procedure and chemotherapy lines. Patients who were submitted to pleurodesis had a protective factor for recurrence, with an HR =0.34 (95% CI, 0.15-0.74, P=0.007). On the other hand, patients submitted to the 1st and 2nd line of palliative CT had, respectively, an HR risk = 2.81 (95% CI, 1.10-7.28, P=0.034) and HR =3.23 (95% CI, 1.33-7.84, P=0.010). CONCLUSIONS: patients receiving the first or second line of systemic treatment have a higher risk of MPE recurrence when compared to patients who underwent MPE treatment before starting the systemic treatment. The definitive treatment of MPE, such as pleurodesis, was associated with a lower risk of MPE recurrence.

Wet M1a non-small cell lung cancer: is it possible to predict recurrence of pleural effusion?

BACKGROUND: The propose was to recognize risk factors of malignant pleural effusion (MPE) recurrence in patients with symptomatic M1a non-small cell lung cancer (NSCLC). METHODS: All patients with NSCLC and MPE submitted to pleural palliative procedures were enrolled in a prospective study. Group I contained patients who had pleural recurrence, and Group II with no pleural recurrence. Prognostic factors for pleural recurrence were identified by univariable analysis, using Fisher's exact test for categorical variables and Student's t test for quantitative variables. Afterwards the significant variables were entered into a multivariable logistic regression analysis (with P<0.05 considered significant). Receiver operating characteristics (ROC) analysis determined the cutoff points for continuous variables. RESULTS: A total of 82 patients were included in the analysis. There were 15 patients (18.3%) in Group I and 67 patients (81.7%) in Group II. Univariable analysis regarding factors affecting postoperative recurrence was: adenosine deaminase concentration in pleural fluid <16 mg/dL (P=0.04), albumin concentration in pleural fluid <2.4 mg/dL (P=0.03), administration of second-line palliative chemotherapy (P=0.018) and type of procedure [therapeutic pleural aspiration (TPA)] (P=0.023). At the multivariable analysis, only the type of procedure (TPA) (P=0.031) was identified as independent predictor of recurrence. CONCLUSIONS: The identification of this factor may assist the choice of the optimal palliative technique; at the first episode of MPE in NSCLC patients and definitive procedure as pleurodesis or indwelling pleural catheter are recommended.

Impact of the delay to start treatment in patients with lung cancer treated in a densely populated area of Brazil.

OBJECTIVES: The aim of this study is to evaluate the access of patients with lung cancer in a densely populated area of São Paulo to the Brazilian Public Health System, focusing on the time spent from symptom onset or initial diagnosis until the beginning of treatment. METHODS: We retrospectively reviewed 509 patients with malignant lung neoplasms who were admitted to a single reference oncology center of the public health system between July 2008 and December 2014. Patients were considered eligible for this study if they were older than 18 years and had not undergone any previous oncology treatment when they were admitted to the institution. The following data were collected from all patients: age, gender, smoking status, tumor staging, time from the when the first symptoms were experienced by the patient to when the patient was diagnosed with cancer, time from the first appointment to cancer diagnosis, and time from when the patient was diagnosed with cancer to the initiation of treatment. RESULTS: The median time from symptom onset to diagnosis was three months. From the first appointment to diagnosis, the median time interval was one month; however, 79% of patients were diagnosed in up to two months. The median time from diagnosis to the start of treatment was one month, but most patients (82.5%) started treatment in up to two months. CONCLUSION: In our highly populated region with preferential access to the public health system, patients are required to wait a relatively long time to effectively begin treatment for lung cancer. This type of study is important to alert medical societies and government health agencies.

Impact of the delay to start treatment in patients with lung cancer treated in a densely populated area of Brazil

OBJECTIVES: The aim of this study is to evaluate the access of patients with lung cancer in a densely populated area of São Paulo to the Brazilian Public Health System, focusing on the time spent from symptom onset or initial diagnosis until the beginning of treatment. METHODS: We retrospectively reviewed 509 patients with malignant lung neoplasms who were admitted to a single reference oncology center of the public health system between July 2008 and December 2014. Patients were considered eligible for this study if they were older than 18 years and had not undergone any previous oncology treatment when they were admitted to the institution. The following data were collected from all patients: age, gender, smoking status, tumor staging, time from the when the first symptoms were experienced by the patient to when the patient was diagnosed with cancer, time from the first appointment to cancer diagnosis, and time from when the patient was diagnosed with cancer to the initiation of treatment. RESULTS: The median time from symptom onset to diagnosis was three months. From the first appointment to diagnosis, the median time interval was one month; however, 79% of patients were diagnosed in up to two months. The median time from diagnosis to the start of treatment was one month, but most patients (82.5%) started treatment in up to two months. CONCLUSION: In our highly populated region with preferential access to the public health system, patients are required to wait a relatively long time to effectively begin treatment for lung cancer. This type of study is important to alert medical societies and government health agencies.

Systematic lymphadenectomy versus sampling of ipsilateral mediastinal lymph-nodes during lobectomy for non-small-cell lung cancer: a systematic review of randomized trials and a meta-analysis.

OBJECTIVES: To re-examine the evidence for recommendations for complete dissection versus sampling of ipsilateral mediastinal lymph nodes during lobectomy for cancer. METHODS: We searched for randomized trials of systematic mediastinal lymphadenectomy versus mediastinal sampling. We performed a textual analysis of the authors' own starting assumptions and conclusion. We analysed the trial designs and risk of bias. We extracted data on early mortality, perioperative complications, overall survival, local recurrence and distant recurrence for meta-analysis. RESULTS: We found five randomized controlled trials recruiting 1980 patients spanning 1989-2007. The expressed starting position in 3/5 studies was a conviction that systematic dissection was effective. Long-term survival was better with lymphadenectomy compared with sampling (Hazard Ratio 0.78; 95% CI 0.69-0.89) as was perioperative survival (Odds Ratio 0.59; 95% CI 0.25-1.36, non-significant). But there was an overall high risk of bias and a lack of intention to treat analysis. There were higher rates (non-significant) of perioperative complications including bleeding, chylothorax and recurrent nerve palsy with lymphadenectomy. CONCLUSIONS: The high risk of bias in these trials makes the overall conclusion insecure. The finding of clinically important surgically related morbidities but lower perioperative mortality with lymphadenectomy seems inconsistent. The multiple variables in patients, cancers and available treatments suggest that large pragmatic multicentre trials, testing currently available strategies, are the best way to find out which are more effective. The number of patients affected with lung cancer makes trials feasible.

Casinga-cheirosa organic extract impairment over Balb-c male mice behavioral phenotype

ABSTRACT Laetia suaveolens (Poepp.) Benth., Salicaceae, popularly known as "casinga-cheirosa", "caferana", or "laranjinha", is native to Brazil but not endemic to this country. A crude organic extract was obtained from the leaves and stem and intraperitoneally administered in male Balb-c mice. Its behavioral effects were evaluated in the open field and elevated plus maze in a two-stage experiment that assessed ten different parameters related to behavior as locomotion, emotionality, and anxiety. In the first stage of the experiment, intraperitoneal the crude organic extract administration dose-dependently impaired locomotion and emotionality 30–120 min after administration. A significant decrease in defecation was observed, which was related to emotionality. No alterations in the elevated plus maze were found; thus, this apparatus was not used in the next stage of the experiment. In the second stage, the previously determined non-lethal dose of 0.1563 g/kg was intraperitoneally administered, which impaired locomotion and rearing frequency and increased immobility time. Necropsy revealed smooth intestine hemorrhage. Rutin, leucoside, nicotiflorin, guaijaverin, and astragalin were isolated from the crude organic extract. This is the first time that these compounds have been identified in L. suaveolens. In conclusion, the crude organic extract impaired locomotion and emotionality and caused hemorrhage in male Balb-c mice, indicating that its consumption can be harmful to humans and animals. The present results provide a basis for further studies on the pharmacology, toxicology, and natural product chemistry of the crude organic extract.

Prognostic factors in patients with malignant pleural effusion: Is it possible to predict mortality in patients with good performance status?

BACKGROUND AND OBJECTIVES: The aim of this study was to identify predictors of mortality only in patients with malignant pleural effusion (MPE) showing good performance status which required pleural palliative procedures. METHODS: All patients with MPE submitted to pleural palliative procedure were enrolled in a prospective study between 2013 and 2014. Patients with Eastern cooperative oncology group (ECOG) score zero, one, and two were considered with good performance status. The possible prognostic factors were tested for significance using the log-rank test (Kaplan-Meier method) and those with significance on univariate analysis were entered into a multivariable Cox model. RESULTS: A total of 64 patients were included in the analysis. Median follow-up time for surviving patients was 263 days. Median survival for the entire cohort was not reached yet. In the multivariate analysis, gastrointestinal primary site (P = 0.006), low albumin concentration in the pleural fluid (P = 0.017), and high serum NLR (P = 0.007) were associated with mortality. CONCLUSION: In our cohort of ECOG 0-2 patients with MPE submitted to pleural palliative procedures, gastrointestinal malignancy compared to other sites, low pleural fluid albumin and high NLR were significantly associated with mortality. The identification of these prognostic factors may assist the choice of the optimal palliative technique. J. Surg. Oncol. 2016;113:570-574. © 2016 Wiley Periodicals, Inc.