Validity of central pain processing biomarkers for predicting the occurrence of oncological chronic pain: a study protocol.

BACKGROUND: Despite recent improvements in cancer detection and survival rates, managing cancer-related pain remains a significant challenge. Compared to neuropathic and inflammatory pain conditions, cancer pain mechanisms are poorly understood, despite pain being one of the most feared symptoms by cancer patients and significantly impairing their quality of life, daily activities, and social interactions. The objective of this work was to select a panel of biomarkers of central pain processing and modulation and assess their ability to predict chronic pain in patients with cancer using predictive artificial intelligence (AI) algorithms. METHODS: We will perform a prospective longitudinal cohort, multicentric study involving 450 patients with a recent cancer diagnosis. These patients will undergo an in-person assessment at three different time points: pretreatment, 6 months, and 12 months after the first visit. All patients will be assessed through demographic and clinical questionnaires and self-report measures, quantitative sensory testing (QST), and electroencephalography (EEG) evaluations. We will select the variables that best predict the future occurrence of pain using a comprehensive approach that includes clinical, psychosocial, and neurophysiological variables. DISCUSSION: This study aimed to provide evidence regarding the links between poor pain modulation mechanisms at precancer treatment in patients who will later develop chronic pain and to clarify the role of treatment modality (modulated by age, sex and type of cancer) on pain. As a final output, we expect to develop a predictive tool based on AI that can contribute to the anticipation of the future occurrence of pain and help in therapeutic decision making.

Aerobic exercise prevents cardiomyocyte damage caused by oxidative stress in early cardiovascular disease by increasing vascularity while L-arginine supplementation prevents it by increasing activation of the enzyme nitric oxide synthase.

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Aerobic exercise prevents cardiomyocyte damage caused by oxidative stress in early cardiovascular disease by increasing vascularity while L-arginine supplementation prevents it by increasing activation of the enzyme nitric oxide synthase

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Sanitary sewage disinfection with ultraviolet radiation and ultrasound.

Currently, the world is facing a horrible situation due to SARS-CoV-2. Though its RNA was found in wastewater, there are still no studies on RNA contamination detected in sewage. Hence, a possible treatment of sewage is suggested in this work. The disinfection stage is extremely important in the treatment of effluents, minimizing the impacts on the receiving body of water and promoting public health. In this context, the sequential use of ultrasound and ultraviolet radiation, on a bench scale, was investigated as a way to improve the disinfection of anaerobically treated effluents. Two types of treated effluents were tested, by septic tank and anaerobic filter, for which, two ultrasound frequencies, 25 and 40 kHz, and four doses of UV, 3.6; 9.0; 18 and 36 mJ cm-2 were applied. Physicochemical and microbiological parameters were observed for individual and sequential assays. The better quality of the anaerobic filter effluent influenced the performance of both processes, decreasing the concentration of organic load and turbidity, even though a concentration of total coliforms and Escherichia coli occurred in the lowest quality effluent (septic tank). The application of ultrasound has a positive effect on the inactivation of total coliforms and E. coli up to 1.0 log and provides better conditions for ultraviolet radiation to be sequentially applied. The UV radiation applied for the septic tank and the anaerobic filter inactivates 2.5 log for total coliforms and 3.5 log for E. coli, respectively. It is suggested that the disinfection methods applied in this work to inactivate gram-negative bacteria (E. coli) can also be applied to secondary treatment effluents, as well as being better tested for viruses, protozoa, and helminths. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-021-03764-7.

HPV infection as a risk factor for atherosclerosis: A connecting hypothesis.

Atheromatous plaques occurring in large arteries are common and life-threatening lesions. Multiple factors are involved in the pathogenesis of atheromatous plaques, such as hyperlipidaemia and hypercholesterolaemia, high blood pressure and chronic systemic inflammation. Recent findings have suggested that infection with high-risk human papillomavirus (HPV) may increase the risk of developing atheromatous plaques. However, HPV is considered a tissue-specific virus with a strong tropism towards squamous epithelial cells, and the mechanisms whereby it may promote the development of atheromas remain unclear. Here, we propose a connecting hypothesis to explain the possible causative role of HPV on atheroma development. We hypothesize that HPV infection may promote atheroma formation in infected patients by enhancing systemic inflammation or by directly targeting blood vessels via nucleic acids carried by extracellular vesicles such as exosomes. The pro-inflammatory effects of HPV and the release of extracellular vesicles by HPV-transformed cells are well documented in scientific literature. Possible experimental approaches to test this hypothesis are also discussed, especially experiments employing transgenic mice bearing HPV16 transgenes. If correct, this hypothesis would have major implications for the prevention of cardiovascular diseases, especially due to the preventable nature of HPV infection through vaccination.

Drinking water treatment by multistage filtration on a household scale: Efficiency and challenges.

Universalising actions aimed at water supply in rural communities and indigenous populations must focus on simple and low-cost technologies adapted to the local context. In this setting, this research studied the dynamic gravel filter (DGF) as a pre-treatment to household slow-sand filters (HSSFs), which is the first description of a household multistage filtration scale to treat drinking water. DGFs (with and without a non-woven blanket on top of the gravel layer) followed by HSSFs were tested. DGFs operated with a filtration rate of 3.21 m3 m-2.d-1 and HSSFs with 1.52 m3 m-2.d-1. Influent water contained kaolinite, humic acid and suspension of coliforms and protozoa. Physical-chemical parameters were evaluated, as well as Escherichia coli, Giardia spp. cysts and Cryptosporidium spp. oocyst reductions. Removal was low (up to 6.6%) concerning true colour, total organic carbon and absorbance (λ = 254 nm). Nevertheless, HMSFs showed turbidity decrease above 60%, E. coli reduction up to 1.78 log, Giardia cysts and Cryptosporidium oocysts reductions up to 3.15 log and 2.24 log, respectively. The non-woven blanket was shown as an important physical barrier to remove solids, E. coli and protozoa.

Single Nucleotide Polymorphisms Influence Histological Type and Grade of Canine Malignant Mammary Tumours.

Histological examination of canine mammary tumours is mandatory for determining the histological type and grade of the lesions, features that provide relevant information regarding the biological behaviour of the disease. Different histological classification systems and grading methods have been used to characterize canine mammary tumours. In this study, the relationship between the genetic profile of 87 female dogs (i.e. single nucleotide polymorphisms [SNPs] in genes known to be involved in mammary carcinogenesis) and the histological type and grade of malignant mammary tumours was assessed. The results demonstrated a significant relationship between genetic variation in genes RAD51, BRCA2, CHEK2, HER2, CDH1, COMT and PGR and these morphological features of the mammary lesions. Specifically, SNPs in RAD51 (rs23623251 and rs23642734), CHEK2 (rs397511718), HER2 (rs24537329) and PGR (rs8875007) were related to aggressive histotypes, with moderate to high histological grade. In contrast, SNPs in BRCA2 (rs23255542), HER2 (rs24537331), CDH1 (rs852280880 and rs850805755) and COMT (rs851328636, rs853133060 and rs85346495) were associated with tumour histotypes of good prognosis and of low histological grade. These data provide preliminary evidence for a genotypic-phenotypic correlation in canine mammary tumours, highlighting the mechanisms of their genesis, development and progression.

PERFORMANCE OF THE INSTADOSETM DOSEMETER FOR INTERVENTIONAL RADIOLOGY AND CARDIOLOGY APPLICATION.

The aim of this article was to verify the performance of the Mirion InstadoseTM dosemeter under clinical conditions and to compare its response in typical X-ray fields used during interventional and cardiology procedures with the TLD-100, usually used for radiation dosimetry. It was also objective of this study to verify the feasibility of using the InstadoseTM dosemeter response at the chest level for estimation of occupational eye lens dose in cardiology and interventional radiology. Initially the response of the dosemeter was tested using continuous X-ray beams and the results showed that the Instadose dosemeter present a satisfactory behavior of the most important dosimetric properties based on the tests as described in the IEC 62387 standard. The measurements performed in clinical conditions showed that the InstadoseTM dosemeter response was comparable to that of TL dosemeters used in interventional radiology and cardiology procedures and there is a correlation between the eye lens doses and the chest doses measured with the InstadoseTM. Based on the results obtained, we recommend the use of the InstadoseTM dosemeter for purposes of occupational whole-body monitoring of medical staff in interventional radiology and cardiology procedures.

Laurus nobilis (laurel) aqueous leaf extract's toxicological and anti-tumor activities in HPV16-transgenic mice.

Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16-/- without treatment, group II: treated HPV16-/-, group III: HPV16+/- without treatment and group IV: treated HPV16+/-). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wild-type animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers.

Ozone therapy prevents the onset of dysplasia in HPV16-transgenic mice-A pre-clinical efficacy and safety analysis.

Infection with high-risk human papillomavirus (HPV), most often HPV16, is associated with the development of anogenital and oropharyngeal cancers. Recently, ozone therapy was reported to have considerable efficacy against rabbit VX2 tumors, induced by the cottontail rabbit papillomavirus. The present study aims to determine whether similar results can be obtained in HPV16-transgenic mice, possibly paving the way for new therapeutic options against HPV-induced cancers. HPV16-transgenic and wild-type, female, 20 weeks-old mice were injected intraperitoneally with medical O3/O2 (80░mL/kg, at O3 50░µg/mL), once a day, for 5 consecutive days. The animals were sacrificed at 25 weeks-old, and skin samples were analyzed histologically to study tumour progression. Blood and internal organ samples were used to study toxicological parameters. 85.7% of untreated transgenic mice showed dysplastic skin lesions, compared with 28.6% of O3-treated mice. This was associated with a marked reduction of dermal inflammation associated with those lesions. No significant changes were observed in any toxicological parameters. These preliminary results support the hypothesis that O3 therapy is effective against papillomavirus-induced lesions, particularly against those induced by the most common high-risk virus, HPV16. Further studies are needed to confirm the mechanisms underlying these effects.

Long-term assessment of a modified tibial tuberosity advancement technique in dogs / Avaliação em longo prazo da técnica de avanço da tuberosidade tibial modificada em cães

The purpose of study was to assess long-term clinical and radiographic aspects of dogs' stifle joints which had undergone a modified tibial tuberosity advancement technique (mTTA). A total of 15 stifles that had undergone mTTA for CCL disease of 11 patients were included in this study. Assessments involved patient's gait analysis, cranial drawer and tibial compression tests, stifle goniometry range of articular motion, thigh and leg girth and radiographic evidence of progression of osteoarthrosis. Variables were compared between operated and healthy limbs and among moments (M0) on the early postop; (M1) 120 days postop; and (M2) approximately 5 years following surgery. A questionnaire regarding owner's perceptions after approximately 5 years of surgery was assessed. Most dogs presented positive response to cranial drawer and tibial compression tests on operated knees. There was also decrease on goniometry and thigh girth and increase in leg girth. Radiographic evidence of progression of osteoarthritis was seen especially on the long-term follow-up (M2). On gait analysis, most animals presented some degree of lameness in different conditions, in contrast to owners' perceptions. Osteoarthritis still develops in dogs following mTTA surgery for CCL disease. However, owners were overall satisfied with their recovery and would be willing to accept indication of mTTA for dogs with ruptured CCL.(AU)

O objetivo deste estudo foi avaliar, em longo prazo, aspectos clínicos e radiográficos do joelho de cães submetidos à técnica modificada de avanço da tuberosidade da tíbia (mTTA). Um total de 15 joelhos de 11 pacientes foram submetidos à mTTA para correção de doença do ligamento cruzado cranial. A avaliação envolvia análise de marcha do paciente, teste de compressão tibial e de gaveta, goniometria do joelho para amplitude articular, circunferência das pernas e coxas e evidência radiográfica de progressão da osteoartrose. As variáveis foram comparadas entre membros operados e saudáveis e entre os momentos (M0) no pós-operatório imediato; (M1) 120 dias de pós-operatório; e (M2) aproximadamente cinco anos após a cirurgia. Foi avaliado um questionário sobre as percepções do proprietário após aproximadamente cinco anos de cirurgia. A maioria dos cães apresentou resposta positiva aos testes de gavetas e de compressão tibial em joelhos operados. Houve também diminuição na goniometria e na circunferência da coxa e aumento do perímetro das pernas. Evidências radiográficas de progressão da osteoartrite foram observadas especialmente no seguimento de longo prazo (M2). Na análise de marcha, a maioria dos animais apresentou algum grau de claudicação em diferentes condições, em contraste com as percepções dos proprietários. A osteoartrite ainda se desenvolve em cães após a cirurgia de mTTA para doença CCL. No entanto, os proprietários estavam, em geral, satisfeitos com a recuperação dos animais e estavam dispostos a aceitar a indicação de mTTA para cães com doença do ligamento cruzado cranial.(AU)

Evaluation of the papilla level adjacent to implants placed in fresh, healing or healed sites: A systematic review.

A better understanding of factors that can lead to papilla formation or recession, such as the type of site where the implant was placed, is of fundamental importance to the aesthetic success of the rehabilitation. The aim of this study was to perform a systematic review of the literature regarding the formation or recession of papilla adjacent to implants placed in fresh, healing or healed sites. The protocol for this study was registered in the PROSPERO database (registration number CRD 42016033784). An electronic search was performed by two independent reviewers who applied the inclusion and exclusion criteria on the PubMed/MEDLINE, Scopus, and Embase databases from January 2005 up to February 2016. The initial screening yielded 1,065 articles, from which 15 were selected for a systematic review after applying the inclusion and exclusion criteria. Nine studies compared fresh and healed sites, four studies compared healing and healed sites, one study compared fresh and healing sites, and one study analysed all three sites. The majority of studies identified by this systematic review showed no difference between groups after the longer follow-up period. The sites where the implants were placed did not have a long-term influence on papilla formation or recession.

Immunogenetic profiling of 23 SNPs of cytokine and chemokine receptor genes through a minisequencing technique: Design, development and validation.

The minisequencing technique offers accuracy and robustness to genotyping of polymorphic DNA variants, being an excellent option for the identification and analyses of prognostic/susceptibility markers in human diseases. Two multiplex minisequencing assays were designed and standardized to screen 23 candidate SNPs in cytokine, chemokine receptor and ligand genes previously associated with susceptibility to cancer and autoimmune disorders as well as to infectious diseases outcome. The SNPs were displayed in two separate panels (panel 1-IL2 rs2069762, TNFα rs1800629, rs361525; IL4 rs2243250; IL6 rs1800795; IL10 rs1800896, rs1800872; IL17A rs8193036, rs2275913 and panel 2-CCR3 rs309125, CCR4 rs6770096, rs2228428; CCR6 rs968334; CCR8 rs2853699; CXCR3 rs34334103, rs2280964;CXCR6 rs223435, rs2234358; CCL20 rs13034664, rs6749704; CCL22 rs4359426; CXCL10/IP-10 rs3921, rs56061981). A total of 305 DNA samples from healthy individuals were genotyped by minisequencing. To validate the minisequencing technique and to encompass the majority of the potential genotypes for all 23 SNPs, 20 of these samples were genotyped by Sanger sequencing. The results of both techniques were 100% in agreement. The technique of minisequencing showed high accuracy and robustness, avoiding the need for high quantities of DNA template samples. It was easily to be conducted in bulk samples derived from a highly admixed human population, being therefore an excellent option for immunogenetic studies.

Lymphoepithelial infiltrate of palatal minor salivary glands: implications for diagnostic work-up.

Benign lymphoepithelial lesions (BLLs) usually affect the parotid glands, resulting in their asymmetrical enlargement. The condition can be associated with Sjögren's syndrome (SS), which in turn may predispose the affected patient to the development of malignant lymphoma. BLLs arising in the intraoral minor salivary glands are rare; such a lesion should prompt the work-up for SS. In some instances, a BLL of a minor salivary gland could represent the initial stage of a mucosa-associated lymphoid tissue (MALT) lymphoma. A case of BLL arising in the palatal minor salivary glands is reported here. The importance of an appropriate diagnostic work-up is emphasized and the relationship of BLL with SS is reinforced.

Are intra-articular injections of hyaluronic acid effective for the treatment of temporomandibular disorders? A systematic review.

This systematic review aimed to investigate whether intra-articular injections of hyaluronic acid (HA) are better than other drugs used in temporomandibular joint arthrocentesis, for the improvement of temporomandibular disorder (TMD) symptoms. Two independent reviewers performed an electronic search of the MEDLINE and Web of Science databases for relevant studies published in English up to March 2016. The key words used included a combination of 'hyaluronic acid', 'viscosupplementation', 'intra-articular injections', 'corticosteroids', or 'non steroidal anti inflammatory agents' with 'temporomandibular disorder'. Selected studies were randomized clinical trials and prospective or retrospective studies that primarily investigated the application of HA injections compared to other intra-articular medications for the treatment of TMD. The initial screening yielded 523 articles. After evaluation of the titles and abstracts, eight were selected. Full texts of these articles were accessed and all fulfilled the inclusion criteria. Intra-articular injections of HA are beneficial in improving the pain and/or functional symptoms of TMDs. However, other drug therapies, such as corticosteroid and non-steroidal anti-inflammatory drug injections, can be used with satisfactory results. Well-designed clinical studies are necessary to identify an adequate protocol, the number of sessions needed, and the appropriate molecular weight of HA for use.

5'UTR +24T>C CR2 is not associated with nasopharyngeal carcinoma development in the North Region of Portugal.

OBJECTIVE: We have analysed the association of the +24T>C polymorphism (rs3813946) in CR2, the cellular receptor for Epstein-Barr virus (EBV), in the susceptibility for the development of nasopharyngeal carcinoma (NPC). METHODS: A retrospective case-control study was developed with peripheral blood samples from 111 individuals with NPC and 608 healthy individuals (controls) from the North region of Portugal. The genotyping analysis was performed by allelic discrimination real-time PCR using a TaqMan(®) SNP Genotyping Assay. RESULTS: The genotype distribution was 62.2% TT, 34.2% TC and 3.6% CC for NPC patients; and 65.0%, 30.6% and 4.4%, respectively, for controls. Our study showed no statistical association between the genotype distribution in controls and all types of NPC (P = 0.717); nevertheless, the analysis showed statistically significant differences (P = 0.038) regarding cases with well- or moderately differentiated types of NPC suggesting that +24CC/CT genotypes are associated with increased risk (OR = 4.16; 95% CI 1.28-15.7; P = 0.016). CONCLUSIONS: This is the first study in Western populations to characterize the association of the CR2 +24T>C polymorphism in NPC development, and our results suggest that more studies are required to clarify the impact on NPC susceptibility in different populations.

Fluorescent membrane markers elucidate the association of Borrelia burgdorferi with tick cell lines

This study aimed to describe the association of Borrelia burgdorferi s.s. with ixodid tick cell lines by flow cytometry and fluorescence and confocal microscopy. Spirochetes were stained with a fluorescent membrane marker (PKH67 or PKH26), inoculated into 8 different tick cell lines and incubated at 30°C for 24 h. PKH efficiently stained B. burgdorferi without affecting bacterial viability or motility. Among the tick cell lines tested, the Rhipicephalus appendiculatus cell line RA243 achieved the highest percentage of association/internalization, with both high (90%) and low (10%) concentrations of BSK-H medium in tick cell culture medium. Treatment with cytochalasin D dramatically reduced the average percentage of cells with internalized spirochetes, which passed through a dramatic morphological change during their internalization by the host cell as observed in time-lapse photography. Almost all of the fluorescent bacteria were seen to be inside the tick cells. PKH labeling of borreliae proved to be a reliable and valuable tool to analyze the association of spirochetes with host cells by flow cytometry, confocal and fluorescence microscopy.

Surgical time and complications of total transvaginal (total-NOTES), single-port laparoscopic-assisted and conventional ovariohysterectomy in bitches / Tempo cirúrgico e das complicações entre as técnicas de ovário-histerectomia totalmente transvaginal (total-NOTES), videoassistida com único portal e convencional em cadelas

The recently developed minimally invasive techniques of ovariohysterectomy (OVH) have been studied in dogs in order to optimize their benefits and decrease risks to the patients. The purpose of this study was to compare surgical time, complications and technical difficulties of transvaginal total-NOTES, single-port laparoscopic-assisted and conventional OVH in bitches. Twelve bitches were submitted to total-NOTES (NOTES group), while 13 underwent single-port laparoscopic-assisted (SPLA group) and 15 were submitted to conventional OVH (OPEN group). Intra-operative period was divided into 7 stages: (1) access to abdominal cavity; (2) pneumoperitoneum; approach to the right (3) and left (4) ovarian pedicle and uterine body (5); (6) abdominal or vaginal synthesis, performed in 6 out of 12 patients of NOTES; (7) inoperative time. Overall and stages operative times, intra and postoperative complications and technical difficulties were compared among groups. Mean overall surgical time in NOTES (25.7±6.8 minutes) and SPLA (23.1±4.0 minutes) groups were shorter than in the OPEN group (34.0±6.4 minutes) (P<0.05). The intraoperative stage that required the longest time was the approach to the uterine body in the NOTES group and abdominal and cutaneous sutures in the OPEN group. There was no difference regarding the rates of complications. Major complications included postoperative bleeding requiring reoperation in a bitch in the OPEN group, while minor complications included mild vaginal discharge in four patients in the NOTES group and seroma in three bitches in the SPLA group. In conclusion, total-NOTES and SPLA OVH were less time-consuming then conventional OVH in bitches. All techniques presented complications, which were properly managed.

O emprego de novas técnicas minimamente invasivas de ovário-histerectomia (OHE) vem sendo estudado em cães com o intuito de otimizar seus benefícios e reduzir os riscos aos pacientes. O presente estudo objetivou comparar o tempo cirúrgico, as complicações e dificuldades técnicas entre as abordagens por total-NOTES transvaginal, videoassistida com único portal e por celiotomia para ovário-histerectomia (OVH) em cadelas. Foram operados 12 animais por total-NOTES (grupo NOTES), 13 pela técnica videoassistida (grupo SPLA) e 15 pela técnica convencional (grupo OPEN). O período intraoperatório foi dividido em sete etapas: (1) acesso à cavidade abdominal; (2) criação do pneumoperitônio; abordagem ao pedículo ovariano direito (3), esquerdo (4) e ao corpo uterino (5); (6) síntese abdominal ou vaginal, realizado em seis de 12 pacientes do grupo NOTES; (7) tempo inoperante. Os parâmetros avaliados foram o tempo cirúrgico total e de cada etapa intraoperatória, a frequência de complicações intra e pós-operatórias e dificuldades técnicas. O tempo cirúrgico total médio dos grupos NOTES (25,7±6,8 minutos) e SPVA (23,1±4,0 minutos) foram menores que o do grupo OPEN (34,0±6,4 minutos) (P<0.05). A etapa intraoperatória que demandou maior tempo de execução foi a abordagem ao corpo uterino para o grupo NOTES, e síntese abdominal e cutânea para o grupo OPEN. Uma cadela do grupo OPEN necessitou de reintervenção para controle de hemorragia como complicação maior, e três cadelas do grupo SPVA apresentaram seroma de ferida cirúrgica como complicações menores. Concluiu-se que as técnicas de total-NOTES e SPLA apresentaram menor tempo cirúrgico que a abordagem convencional de OVH em cadelas. Todas as técnicas apresentaram complicações que foram adequadamente manejadas.

CYP2D6*4 polymorphism: A new marker of response to hormonotherapy in male breast cancer?

BACKGROUND: Tamoxifen remains the standard hormonotherapy for Male breast cancer patients (MBC). Previous studies, in women, tried to evaluate the impact of CYP2D6 polymorphisms in tamoxifen efficacy with conflicting results. Herein we analyze the relation between CYP2D6*4 polymorphism and survival in MBC patients. PATIENTS AND METHODS: Fifty-three patients, proposed to tamoxifen in adjuvant setting, were enrolled. Clinical information was collected from records and histological revision with additional immunochemistry analysis was done to better characterize the tumors. Comprehensive CYP2D6*4 genotyping from blood or tumor tissue was performed and translated into two predicted metabolic activity groups. RESULTS: Patients included in the two CYP2D6*4 groups did not differ concerning to age, histological characteristics, and primary treatments performed. Median age at diagnosis was 63 years-old and patients were submitted at least to mastectomy and adjuvant hormonotherapy. Recurrence was observed in 7 patients (13.2%) and 13 patients (25.5%) died with a 5-year disease-free survival of 86.2%. The poorer metabolizer group had a high risk for recurrence (p = 0.034) and this outcome effect remains in different subgroups: in tumors larger than 2 cm (p < 0.001), nodal status, N0 vs N+ (p = 0.04) and in advanced stage, stage III (p < 0.001). Poorer metabolizer patients had also a worse overall survival when tumors were larger than 2 cm (p = 0.03). CONCLUSIONS: In our series, there was an association between CYP2D6*4 polymorphism and a probability of recurrence, with a consistent effect in risk groups defined by classic prognostic factors. Multicentric studies with larger samples are needed to validate these results.