The cancer registry as an ally in monitoring treatment effectiveness.

OBJECTIVE: To evaluate if the cancer registry database can be used to monitor treatment effectiveness using nivolumab treatment of non-small cell lung cancer (NSCLC) as an example. METHOD: An observational inception cohort was used, where all registered cases of NSCLC with authorisation to initiate treatment with nivolumab were monitored retrospectively to evaluate disease characteristics and response to prior treatments. Current exposure to nivolumab was prospectively characterised and treatment outcomes classified based on the clinical information registered in the patient medical record. The main outcome measure used to assess treatment effectiveness was overall survival (OS). Secondary outcomes considered were progression free survival (PFS) as a measure of effectiveness and occurrence of Adverse Drug Reaction (ADRs) as a measure of safety. Data were analysed using SPSS, version 24. RESULTS: A total of 115 patients received treatment with nivolumab for NSCLC, between November 1st 2015 and July 31st 2016, and were registered in the database. The majority were non-squamous type (n=107). The median OS was 11.4 months {CI95%: 11.1-11.7}, with a 1-year survival of 44%, in line with clinical trial data. Median PFS was 5.4 months {CI95%: 2.8-7.9}. Treatment was discontinued in 82 cases, most frequently due to disease progression. There were 38 cases of ADRs documented in the patient medical chart, 21 of which led to treatment discontinuation. CONCLUSION: The analysed data suggest that the cancer registry is a powerful tool to monitor treatment effectiveness, although considerable investment is needed to improve the medical culture of recording treatment exposure, particularly documentation of ADRs.

High COX-2 expression is associated with increased angiogenesis, proliferation and tumoural inflammatory infiltrate in canine malignant mammary tumours: a multivariate survival study.

COX-2 expression affects mammary tumourigenesis by promoting angiogenesis and cell proliferation, encouraging metastatic spread and tumour-associated inflammation. Samples of canine mammary tumours (n = 109) were submitted to immunohistochemistry to detect COX-2, CD31, VEGF, Ki-67, CD3 and MAC387 expression. Concurrent high expression of COX-2/CD31, COX-2/VEGF, COX-2/Ki-67, COX-2/CD3 and COX-2/MAC was associated with elevated grade of malignancy, presence of intravascular emboli and presence of lymph node metastasis. Tumours with high COX-2 (P < 0.001) and tumours with concurrent expression of high COX-2 and high CD31 (P = 0.008); high VEGF (P < 0.001); high Ki-67 (P < 0.001); high CD3+ T-lymphocytes (P = 0.002) and elevated MAC387 macrophages (P = 0.024) were associated with shorter overall survival (OS) time. Interestingly the groups with high COX-2/CD31 and high COX-2/VEGF retained their significance after multivariate analysis arising as independent predictors of OS. Present data highlight the importance of COX-2 in canine mammary tumourigenesis.

Ki-67 and PCNA Expression in Canine Mammary Tumors and Adjacent Nonneoplastic Mammary Glands: Prognostic Impact by a Multivariate Survival Analysis.

The assessment of tumor proliferation has been considered a determining prognostic factor in canine mammary tumors (CMTs). However, no studies have assessed the prognostic importance of proliferation in adjacent nonneoplastic mammary glands. We included 64 CMTs (21 benign and 43 malignant) and studied the proliferation index (PI) of Ki-67 and proliferating cell nuclear antigen (PCNA) together with several clinicopathological characteristics. A positive and statistically significant correlation between the PI of Ki-67 and PCNA in tumors and adjacent nonneoplastic mammary glands was observed in benign and malignant tumors. Tumor size, skin ulceration, histological type, mitotic index, nuclear grade, differentiation grade, histological grade of malignancy, lymph node metastasis, Ki-67, and PCNA expression in tumors and adjacent nonneoplastic mammary glands were statistically associated with overall survival by univariate analysis in malignant cases (n = 43). Histological grade of malignancy and high intratumoral PCNA retained their significance by multivariate analysis arising as independent predictors of overall survival. Interestingly, the PI of Ki-67 and PCNA of adjacent nontumoral mammary glands were associated with clinicopathological features of tumor aggressiveness and shorter overall survival, demonstrating the need to better explore this adjacent non-neoplastic tissue.

Tumour-associated macrophages are associated with vascular endothelial growth factor expression in canine mammary tumours.

Tumour-associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin-fixed paraffin-embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease.

Concurrent expression of cyclo-oxygenase-2 and epidermal growth factor receptor in canine malignant mammary tumours.

Canine mammary tumours (CMTs) are reported to express cyclo-oxygenase (COX)-2 and epidermal growth factor receptor (EGFR); however, no studies have evaluated concurrent expression of these proteins. In this study, 43 malignant CMTs were evaluated immunohistochemically for concurrent expression of COX-2 and EGFR and expression was correlated with malignancy. High COX-2 expression was associated with tumour size (P = 0.033), mitotic index (P = 0.040), nuclear grade (P = 0.021), histological grade of malignancy (P = 0.020) and lymph node metastasis (P = 0.029). High EGFR immunoreactivity was associated with tumour size (P = 0.001), necrosis (P = 0.001), mitotic index (P = 0.022), histological grade of malignancy (P = 0.041) and lymph node metastasis (P = 0.005). Simultaneous high-expression of COX-2 and EGFR was associated with high-nuclear grade (P = 0.049), high-histological grade of malignancy (P = 0.031) and the presence of lymph node metastasis (P = 0.025). A positive correlation between COX-2 and EGFR expression (r = 0.474; P = 0.001) was also observed. These results suggest that combined use of selective inhibitors of COX-2 and EGFR may be a useful approach to the treatment of malignant CMTs.

Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy.

PURPOSE: Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first-line drug in the treatment of epilepsy. We evaluated the efficacy of CLB as add-on therapy in patients with refractory partial epilepsy. METHODS: This was an open, retrospective study, conducted at the epilepsy clinic of our university hospital. All patients had chronic epilepsy and were being evaluated for epilepsy surgery. CLB was introduced as add-on therapy (starting with 10 mg/ day) in patients with previous failure of at least two AEDs. Information was obtained from clinical notes and follow-up visits. RESULTS: We evaluated 97 patients, 37 men and 60 women. Ages ranged from 15 to 70 years (mean, 35.8 years). Etiology of epilepsy was hippocampal atrophy in 67 (69%), cortical dysgenesis in nine (9.3%), and other etiologies in nine (9.3%). In 12 (12.3%) patients, the etiology of epilepsy was not identified despite clinical and neurologic investigation. Patients used CLB for a period ranging from 1 month to 7 years and 9 months (mean, 16.7 months) with doses ranging from 10 to 60 mg/day (mean, 29.7 mg/day). Seven (7.2%) patients were seizure free, 48 (49.4%) had > or =50% of improvement in seizure control, 39 (40.2%) had <50% of improvement in seizure control, and in three (3.1%), no data were available. CONCLUSIONS: We conclude that CLB may have efficacy equivalent to that of the new AEDs when used as add-on therapy in patients with refractory epilepsy. CLB should be considered an economic alternative in the treatment of patients with refractory epilepsy.

Molecular epidemiology of HIV-1 in Brazil: high prevalence of HIV-1 subtype B and identification of an HIV-1 subtype D infection in the city of Rio de Janeiro, Brazil. Evandro Chagas Hospital AIDS Clinical Research Group.

HIV-1-positive individuals were recruited from January 1993 to December 1996 from several cohorts receiving follow-up in the city of Rio de Janeiro, Brazil, to evaluate HIV-1 genetic variability and the potential association with modes of transmission. HIV-1 subtyping was carried out using the heteroduplex mobility assay (HMA), and those samples corresponding to the typical Brazilian subtype B variant were further identified based on the Fok I restriction fragment length polymorphism (RFLP). DNA sequencing was performed to evaluate one case of subtype D infection. From the 131 HIV-1-positive individuals analyzed, 106 (80.9%) could be identified as infected by subtype B and 20 (15.3%) by subtype F. One of the samples (0.8%) was classified as subtype D. DNA samples from 4 patients (3.0%) did not yield polymerase chain reaction (PCR)-amplified products to be typed. Based on the Fok I RFLP, 39 of the 106 subtype B samples (37%) were identified as corresponding to the typical Brazilian subtype B variant containing the GWGR motif at the tip of the V3 loop. No statistically significant association could be detected between HIV-I subtypes and modes of transmission, exposure categories, or gender. This is the first reported case of HIV-1 subtype D infection in Brazil.

[Early physical conditioning of patients surgically treated for myocardial revascularization. Influence on the functional capacity]. / Condicionamento físico precoce de pacientes submetidos à cirurgia de revascularização do miocárdio. Influência sobre a capacidade funcional.

PURPOSE: To evaluate the early physical conditioning (PC) effect [initiated 15 days after the myocardial revascularization surgery (MRS)] in the functional capacity. METHODS: Twenty-two male patients (mean-age of 52y-o), divided in two groups (A and B, 11 patients each), were studied. Group A started PC 3 months after MRS (phase III), with a training intensity of about 70% of the maximum heart rate reserve, during three months, three sessions per week with one hour duration. Group B started PC 15 days after the MRS (fase II), with a training intensity up to five metabolic unities, three times a week, 1 hour and 15 duration. The post-MRS period of three months was designated as the time I (beginning of fase III) and six months as time 2. Stress test, Kraus-Weber flexibility test, coxo-femural flexibility test (flexion, elevation and abduction) and scapule-umeral flexibility test (flexion, extension and abduction) were applied. RESULTS: The maximum oxygen uptake and the total work increased significantly from time 1 to time 2 in both groups, but there was no significant difference between the two groups, either in time 1 or 2. Flexibility in the Kraus-Weber test and in the scapule-umeral flexibility test when in flexion, were significantly greater in group B than A, in both times (1 and 2). Other flexibility variables studied show no significant difference, neither between the studied groups nor in the times 1 and 2 of evaluation. CONCLUSION: Early PC after MRS increased the value of two variables that measure flexibility. However, it has not increased other flexibilities variables and the aerobic capacity.

Chlamydia trachomatis in cervical uterine irradiated cancer patients.

Twenty-two women with uterine carcinoma with morphological alterations postradiation treatment suggestive of Chlamydia trachomatis infection were analyzed by direct immunofluorescence. The diagnosis was confirmed in 12 (54.4%) cases. Discussions of the presence of Chlamydia in irradiated cells were not found in the literature. This finding may signify a posttherapeutic morbidity or a preradiation infection.

[Chlamydia trachomatis in smears of irradiated uterine cervix: cytologic and immunocytochemical aspects]. / "Chlamydia trachomatis" em esfregaços de colo uterino irradiado: aspectos citológicos e imunocitoquímicos.

Some authors recently suggested the role of Chlamydia trachomatis as a potentiating agent of female genital tract neoplasias. Cervicovaginal smears of women with uterine carcinoma treated with radiotherapy are analyzed in the present work. A series of such smears showed morphological changes suggestive of Chlamydia infection with the Papanicolaou stain. Confirmation of the presence of such agent was done using an avidin-biotin-peroxidase technique. A higher prevalence of Chlamydia in the group of patients with carcinoma of the uterus treated with irradiation than in the population without ionizing treatment was verified. The presence of cells with radiotherapic changes infected by Chlamydia is a new finding in cytology.

An outbreak of cryptosporidiosis in a hospital day-care centre.

The investigation of an outbreak of cryptosporidiosis in a hospital day-care centre is reported. Twenty-eight (27%) children and one member of the staff were infected. Most of the cases were symptomatic and the major presenting symptom was watery diarrhoea. Shedding of oocysts continued for a mean of 12 days after diarrhoea had subsided and most of the cases were still excreting oocysts when the first follow-up sample was examined. Intermittent shedding or a carrier state were not seen in any of the cases. Giardia intestinalis cysts were detected in 19 children, 7 of whom showing mixed infection with Cryptosporidium sp., but this association was not statistically significant. All cases recovered without specific therapy. No definite proof could be found to demonstrate the source of the outbreak or the route of transmission but some observations suggesting person-to-person transmission are discussed.

The effects of age, sex and diet on the clastogenic action of cyclophosphamide in mouse bone marrow.

7-week-old and 12-week-old mice of both sexes received either a control or protein-deficient diet for 3 weeks. Afterwards, they were given a single dose of cyclophosphamide (0.5 mg/10 g b.wt.) before being sacrificed. The relationship between age and the clastogenic action of cyclophosphamide can be observed in the bone marrow cells of male mice but not in those of female mice. 12-week-old males on a 75% protein-deficient diet have a lower frequency of cells with cyclophosphamide-induced chromosome aberrations than has the control group. On the contrary, 7-week-old males and females, and 12-week-old females, show that protein-deficient diets act synergistically with the clastogenic action of cyclophosphamide. These results are discussed taking the metabolism of the drug into account. Animal age also plays a role in the formation of chromosome rearrangements; this type of aberration is significantly more frequent in younger animals of both sexes than in older ones exposed to the drug.