Lymphovascular invasion in hormone-positive, human epidermal growth factor-negative, low-burden axillary disease in early breast cancer patients tested for oncotype DX recurrence score.

Introduction: The oncotype DX recurrence score (ODX-RS) is a validated 21-gene assay that can quantify the recurrence risk and assess the likelihood of adjuvant chemotherapy benefit in breast cancer. The presence of lymphovascular invasion (LVI) in breast cancer patients is regarded as a predictor for worse prognosis. This study sought to explore the association of ODX-RS with LVI in oestrogen receptor-positive, human epidermal growth factor receptor-2-negative, low-burden nodal disease, early breast cancer. Material and methods: After clinical improvement unit approval, an institutional database was queried to identify the breast cancer cases diagnosed in the period between 2017-2021 that fulfilled the inclusion criteria. The total resected tumours comprised 107 in 102 patients (5 patients had bilateral disease). The data related to patients' age and tumour grade, LVI detection, nodal status, and ODX-RS were analysed. Results: Lymphovascular invasion was identified in 32.6% of 107 tumours. In the age group > 50 years, 13 tumours had lymphovascular invasion (LVI +ve), 9 tumours had ODX-RS < 15 (69%), and only one tumour (8%) had ODX-RS ≤ 25, and this is associated with substantial chemotherapy benefit. In the age group ≤ 50 years, 21 tumours were LVI +ve, and 18 tumours had ODX-RS ≤ 25 (86%), which is associated with no chemotherapy benefit; only 3 tumours (14%) had ODX-RS > 25, and this indicated substantial chemotherapy benefit. Conclusions: This study revealed that in the targeted patient population lympho-vascular invasion did not have a statistically significant impact on ODX-RS (p = 0.29).

The Challenge of COVID-19: The Biological Characteristics and Outcomes in a Series of 130 Breast Cancer Patients Operated on During the Pandemic.

Background: The worldwide outbreak of the 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China close to the end of 2019. We analyse the clinical characteristics and management outcomes of a small group of patients who have been treated in the early stage of the COVID-19 disease, and discuss the impact of the pandemic on the service delivered to breast cancer patients. Material Methods: We analysed a cohort of 130 breast cancer patients who underwent elective surgical procedures during the early period of COVID-19. The patients were operated on in the period from March 16th, 2020 to May 18th, 2020. Results: All the patients were female, with an age range of 33-88 years, with a median age of 57.6 years. Most of the cases were admitted as a day case surgery after passing through a preoperative screening pathway, which was developed gradually. Patients were contacted by phone after their surgery to ensure that they have had no symptoms and were reviewed in person two weeks after the procedure with histology results. Only one patient developed COVID-19 symptoms after surgery and recovered. Conclusions: Early and careful implementation of modified practice policies during emerging situation of viral pandemics will reduce the risk of perioperative complications, reduce the risk of patient to staff to patient transmission and minimize the negative impact of COVID-19 on breast cancer management.

Breast Adenoid Cystic Carcinoma in a patient with Previous Contra-lateral Breast Ductal Carcinoma in-situ: A Case Report.

Breast adenoid cystic carcinoma (BACC) is a rarely encountered malignant breast neoplasm with a favourable outcome, despite its triple-negative receptor status. It is comprising less than 0.1% of all breast cancers. The more usual primary site of the adenoid cystic carcinoma is seen in the salivary glands, however BACC prognosis is better than the one for salivary gland and also than that of other breast invasive carcinoma. BACC also known to have fewer lymph node metastases as well as fewer distant metastases, hereby we present 73 years old female with previous history of breast ductal carcinoma in-situ, then developed contralateral breast adenoid cystic carcinoma.

Colonic Goblet Cell Carcinoid: Rarity of a Rarity! A Case Report and Review of Literature.

Goblet cell carcinoids (GCC) are extremelyrare neuroendocrine tumours, and characterised by their unique combination of two types of cancer cells âÃÂ" neuroendocrine (carcinoid) and epithelial (adeno-carcinoma). In spite of the fact that GCC is regarded as Neuro-Endocrine Tumour (NET), it does not illicit carcinoid syndrome. GCC usually arises in the appendix and accounting for less than 14% of all appendiceal tumours.Primary extra-appendiceal GCC have been reported as stomach, duodenum, small intestine, colon and rectum. The paper presents a rare case of GCC of the ascending colon in a 57-year-old male.

Breast Metastasis as a Presentation of Malignant Melanoma.

The majority of malignant breast lesions are primary tumors originated from breast tissue. These primary breast cancers usually metastasize to lymph nodes, lungs, bones and brain. Metastases from cancers of other organs to the breast are very rare, but have been encountered in patients with malignant melanoma, carcinoid tumors or lung carcinoma. The present paper reports a case of mammary metastasis from malignant melanoma.

Aerobic exercise inhibits obesity-induced respiratory phenotype.

PURPOSE: Obesity results in decreased lung function and increased inflammation. Moderate aerobic exercise (AE) reduced lung inflammation and remodeling in a variety of respiratory disease models. Therefore, this study investigated whether AE can attenuate a diet-induced obesity respiratory phenotype; including airway hyper-responsiveness (AHR), remodeling and inflammation. METHODS: Sixty C57Bl/6 male mice were distributed into four groups: control lean (CL), exercise lean (EL), obese (O) and obese exercise (OE) groups (2 sets of 7 and 8 mice per group; n = 15). A classical model of diet-induced obesity (DIO) over 12 weeks was used. AE was performed 60 min/day, 5 days/week for 5 weeks. Airway hyperresponsiveness (AHR), lung inflammation and remodeling, adipokines and cytokines in bronchoalveolar lavage (BAL) was determined. RESULTS: A high fat diet over 18 weeks significantly increased body weight (p < .0001). Five weeks of AE significantly reduced both AHR and pulmonary inflammation. AHR in obese mice that exercised was reduced at the basal level (p < .05), vehicle (PBS) (p < .05), 6.25 MCh mg/mL (p < .05), 12.5 MCh mg/mL (p < .01), 25 MCh mg/mL (p < .01) and 50 MCh mg/mL (p < .05). Collagen (p < .001) and elastic (p < .001) fiber deposition in airway wall and also smooth muscle thickness (p < .001) were reduced. The number of neutrophils (p < .001), macrophages (p < .001) and lymphocytes (p < .01) were reduced in the peribronchial space as well as in the BAL: lymphocytes (p < .01), macrophages (p < .01), neutrophils (p < .001). AE reduced obesity markers leptin (p < .001), IGF-1 (p < .01) and VEGF (p < .001), while increased adiponectin (p < .01) in BAL. AE also reduced pro-inflammatory cytokines in the BAL: IL-1ß (p < .001), IL-12p40 (p < .001), IL-13 (p < .01), IL-17 (p < .001, IL-23 (p < .05) and TNF-alpha (p < .05), and increased anti-inflammatory cytokine IL-10 (p < .05). CONCLUSIONS: Aerobic exercise reduces high fat diet-induced obese lung phenotype (AHR, pulmonary remodeling and inflammation), involving anti-inflammatory cytokine IL-10 and adiponectin.

Evaluating the Effect of 3% Papain Gel Application in Cutaneous Wound Healing in Mice.

While the US Food and Drug Administration has not approved the use of 3% papain gel in the United States, the authors feel this study adds to the literature regarding its use. INTRODUCTION: The aim of this study was to evaluate the effect of 3% papain gel on wounds in mice. MATERIALS AND METHODS: Thirty healthy C57BL mice (25-30 g) aged 10 weeks were randomly divided into 2 groups: mice treated with 3% papain gel and mice treated with placebo gel. Skin incisions were performed with a 6-mm metallic punch with a cutting blade edge. On days 3 and 7 after creating the lesion, the mice were euthanized and lesion samples were collected. The lesion samples were processed and sectioned into 3 fragments of skin to be stained with 3 types of dye: hematoxylin and eosin, Picrosirius red, and Weigert. In addition, immunohistochemical analysis (α-SM actin and Ki67) followed by real-time polymerase chain reaction (PCR) protocol was performed on the samples. RESULTS: On gross examination, the 3% papain-treated group took less time to heal the wounds compared with the control. On day 7, microscopic examination showed the 3% papain-treated group had lower numbers of inflammatory cells, increased neovascularization, and improved organization of collagen and elastic fibers. Using PCR analysis, the 3% papain-treated group showed a significant increase in transforming growth factor beta and interleukin-6 expression compared with the control (P < .05). CONCLUSION: Due to a reduced local inflammatory response, increased angiogenesis, and improved organization of collagen deposition, these findings demonstrate 3% papain gel can improve cutaneous wound healing in mice.

Treatment with Parkinsonia aculeata combats insulin resistance-induced oxidative stress through the increase in PPARγ/CuZn-SOD axis expression in diet-induced obesity mice.

Parkinsonia aculeata L. (Caesalpiniaceae) is a traditional ethnomedicine and has been used for the empiric treatment of hyperglycemia, without scientific background. Mechanistic analyses at molecular level from the antioxidant mechanism observed by P. aculeata are required. Herein the effects of the treatment by hydroethanolic extract partitioned with ethyl acetate of P. aculeata aerial parts (HEPa/EtOAc) in mice fed a high-fat diet that share many obesity phenotypes with humans were evaluated. The animals were treated orally with HEPa/EtOAc (125 and 250 mg/kg/day) and pioglitazone (5 mg/kg/day), for 16 days. After the treatment, HEPa/EtOAc reduced fasting serum glucose and insulin levels, as well as homeostasis model assessment for insulin resistance. In addition, an improvement in glucose intolerance was also observed. Indeed, a reduction in the circulating levels of TNF-α and IL-6 was also observed. Furthermore, at molecular level, it was demonstrated that the HEPa/EtOAc treatment was able to improve these physiological parameters, through the activation of peroxisome proliferator-activated receptor γ (PPARγ) per si, as well as the enhancement of antioxidant mechanism by an increase in PPARγ/Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD) axis expression in liver and adipose tissue. In sum, P. aculeata is effective to improve insulin resistance in a mouse model of obesity and this effect seems to involve the antioxidant and anti-inflammatory mechanisms through the increase in PPARγ/CuZn-SOD axis expression.

Agreement analysis between critical power and intensity corresponding to 50% ∆ in cycling exercise / Análise de concordância entre a potência crítica e a intensidade correspondente ao 50% ∆ no exercício de ciclismo

Abstract The purpose of this study was to determine the level of agreement between critical power (CP) and intensity corresponding to 50% of the difference (50% ∆) between oxygen uptake (VO2) at lactate threshold (LT) and maximal oxygen uptake (VO2max) in untrained subjects during cycling exercise. Fifteen healthy male subjects (age: 26.0 ± 3.5 years; body weight: 76.6 ± 10.4 kg; height: 178.2 ± 7.6 cm) volunteered to participate in the study. Each subject performed a series of tests to determine LT, VO2LT, CP, VO2CP, 50% ∆, VO250% ∆, and VO2max. The values LT, CP, VO2CP, 50% ∆, VO250% ∆ and VO2max were 109 ± 15 W, 1.84 ± 0.23 L.min-1, 207 ± 17 W, 2.78 ± 0.27 L.min-1, 206 ± 19 W, 2.77 ± 0.29 L.min-1, and 3.71 ± 0.49 L.min-1, respectively. No signficant difference was found between CP and 50% ∆ (t = 0.16; p = 0.87) or between VO2CP and VO250% ∆ (t = 0.12; p = 0.90). However, the bias ± 95% limits of agreement for comparison between CP and 50% ∆ and between VO2CP and VO250% ∆ were 1 ± 27 W (0.3 ± 14.1%) and 0.01 ± 0.24 L.min-1 (0.2 ± 8.9%), respectively. In summary, the mean CP and 50% ∆ values were not significantly different. However, considering the limits of agreement between the two intensities, CP estimated based on 50% ∆ might result in a remarkable error when the absolute variability of individual differences is taken into account.

Resumo A proposta deste estudo foi determinar o nível de concordância entre a potência crítica (PC) e a intensidade correspondente a 50% da diferença (50% ∆) entre o consumo de oxigênio (VO2) no limiar de lactato (LL) e o consumo máximo de oxigênio (VO2max) em sujeitos não treinados durante o exercício de ciclismo. Quinze sujeitos saudáveis do sexo masculino (idade: 26,0 ± 3,5 anos; massa corporal: 76,6 ± 10,4 kg; estatura: 178,2 ± 7,6 cm) participaram deste estudo. Cada sujeito realizou uma série de testes para determinar o LL, VO2.LL, PC, VO2.PC, 50% ∆, VO250% ∆ e VO2max. Os valores de LL, VO2LL, PC, VO2PC, 50% ∆, VO250% ∆ e VO2max foram 109 ± 15 W, 1,84 ± 0,23 L.min-1, 207 ± 17 W, 2,78 ± 0,27 L.min-1, 206 ± 19 W, 2,77 ± 0,29 L.min-1 e 3,71 ± 0,49 L.min-1, respectivamente. Nenhuma diferença significavita foi encontrada entre a PC e o 50% ∆ (t = 0.16; p = 0.87) e entre o VO2PC e o VO250% ∆ (t = 0.12; p = 0.90). Entretanto, o bias ± 95% dos limites de concordância para as comparações entre a PC e o 50% ∆ e entre o VO2PC e o VO250% ∆ foram 1 ± 27 W (0,3 ± 14,1%) e 0,01 ± 0,24 L.min-1 (0,2 ± 8,9%), respectivamente. Em resumo, os valores médios de PC e 50% ∆ não foram significativamente diferentes. No entanto, a PC estimada pelo 50% ∆ pode resultas em um erro significativo quando a cariabilidade individual absoluta é considerada.

Parkinsonia aculeata (Caesalpineaceae) improves high-fat diet-induced insulin resistance in mice through the enhancement of insulin signaling and mitochondrial biogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: The search for natural agents that minimize obesity-associated disorders is receiving special attention. Parkinsonia aculeata L. (Caesalpineaceae) has long been used in Brazil as a hypoglycaemic herbal medicine, without any scientific basis. AIMS OF THE STUDY: In this context, we aimed to use molecular and physiological methods to study the effect of a hydroethanolic extract partitioned with ethyl acetate from the aerial parts of Parkinsonia aculeata (HEPa/EtOAc) on insulin resistance in a mouse model of diet-induced obesity (DIO). MATERIAL AND METHODS: Firstly, C57BL/6J mice were fed either with standard rodent chow diet or a high-fat diet (HFD) for 12 consecutive weeks. Then, the animals were treated with HEPa/EtOAc at two doses (125 and 250mg/kg/day) or metformin (200mg/kg/day) for 16 days. At the end of the experiment, body weight, fat pad weight, fasting serum glucose (FSG), insulin (FSI) and leptin were measured. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. Glucose, insulin and pyruvate tolerance tests were performed. The expression and phosphorylation of IRß(tyr), Akt(ser473), AMPKα and PGC1α in liver, muscle and adipose tissue were determined by Western blot analyses. RESULTS: Herein we demonstrate for the first time an improvement in insulin resistance following HEPa/EtOAc administration in obese mice, as shown by increased glucose, insulin and pyruvate tolerance, as well as an improvement in FSG, FSI, HOMA-IR and circulating leptin levels, which together are in part due to enhancement of the insulin signaling pathway in its main target tissues. Surprisingly, the increase in activation of the AMPKα-PGC1-α axis by HEPa/EtOAc was similar to that produced by metformin treatment in the liver and muscle tissues. CONCLUSION: In conclusion, P. aculeata appears to be a source of therapeutic agent against obesity-related complications.

Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma.

The phenotype and function of cells enriched in tumor-propagating activity and their relationship to the phenotypic architecture in multiple myeloma (MM) are controversial. Here, in a cohort of 30 patients, we show that MM composes 4 hierarchically organized, clonally related subpopulations, which, although phenotypically distinct, share the same oncogenic chromosomal abnormalities as well as immunoglobulin heavy chain complementarity region 3 area sequence. Assessed in xenograft assays, myeloma-propagating activity is the exclusive property of a population characterized by its ability for bidirectional transition between the dominant CD19(-)CD138(+) plasma cell (PC) and a low frequency CD19(-)CD138(-) subpopulation (termed Pre-PC); in addition, Pre-PCs are more quiescent and unlike PCs, are primarily localized at extramedullary sites. As shown by gene expression profiling, compared with PCs, Pre-PCs are enriched in epigenetic regulators, suggesting that epigenetic plasticity underpins the phenotypic diversification of myeloma-propagating cells. Prospective assessment in paired, pretreatment, and posttreatment bone marrow samples shows that Pre-PCs are up to 300-fold more drug-resistant than PCs. Thus, clinical drug resistance in MM is linked to reversible, bidirectional phenotypic transition of myeloma-propagating cells. These novel biologic insights have important clinical implications in relation to assessment of minimal residual disease and development of alternative therapeutic strategies in MM.

Regulation of multiple myeloma survival and progression by CD1d.

Down-regulation of conventional human leukocyte antigen (HLA) class I and II molecules from the surface of tumor cells is an important mechanism for tumor immune evasion, survival, and progression. Whether CD1d, a nonconventional, glycolipid-presenting HLA class I-like molecule instructing the function of the immunoregulatory invariant NKT cells can affect tumor cell survival is not known. Here we show that CD1d is highly expressed in premalignant and early myeloma, but with disease progression its expression is reduced and eventually in advanced stages and myeloma cell lines is lost altogether, suggesting that CD1d impacts negatively on myeloma cell survival. Consistent with this, engagement of CD1d by anti-CD1d monoclonal antibodies (mAbs) induces cell death of myeloma cell lines with restored CD1d expression and primary myeloma cells. Cell death induced by monoclonal antibody engagement of CD1d is associated with overexpression of proapoptotic Bax and mitochondrial membrane potential loss but it is caspase-activation independent; in addition, it requires the cytoplasmic tail but not the Tyr residue critical for lysosomal sorting of CD1d. Finally, anti-CD1d cooperates with antimyeloma agents in the killing of myeloma cells. Thus, this work provides evidence linking a novel function of CD1d in the regulation of cell death with tumor survival and progression in humans.

Myeloproliferative disorder as the cause of peripheral ischemia in a young patient.

A 35-year-old patient with rest pain and peripheral gangrene was referred with a diagnosis of Takayasu's disease but had myeloproliferative disorder (primary thrombocythemia). The angiogram revealed surgically noncorrectable small vessel occlusive disease with no evidence of atheroma. Medical therapy with cytotoxic and antiplatelet agents achieved satisfactory results with excellent wound healing after surgical amputation of necrotic tissue. The need for early diagnosis of this condition is emphasized.

Case 37: Neutropenia and macrocytosis in a middle-aged man.

A myelodysplastic syndrome (MDS) was suspected in a middle-aged man who presented with neutropenia and macrocytosis. The correct non-neoplastic diagnosis was not made for 5 years. It is of crucial importance to exclude treatable causes of cytopenia and dysplasia when MDS is suspected.

Mesenteric adipose tissue alterations resulting from experimental reactivated colitis.

BACKGROUND: Adipose tissue secretes a large number of hormones that act either locally or at distant sites, modulating immune responses, inflammation, and many endocrine and metabolic functions. Abnormalities of fat in the mesentery have been long recognized in surgical specimens as characteristic features of Crohn's disease; however, the importance of this in chronic inflammatory disease is unknown. Additionally, adipocytes in depots that enclose lymph nodes or other dense masses of lymphoid tissue have many site-specific physiological properties. METHODS: In this study, the alterations of mesenteric and perinodal mesenteric adipose tissue during experimental colitis, induced by repeated intracolonic trinitrobenzene sulfonic acid instillations, were evaluated, focusing on morphological and activity alterations and the adipocytokine production profile. RESULTS: After a 35-day protocol, the colitis animals presented greater mesenteric fat masses despite their lower body weights. Another adipose tissue depot, epididymal adipose tissue, was also evaluated and no change in mass was observed. The mesenteric adipocyte from colitis animals had a reduced diameter, normal PPAR-gamma-2 expression, and higher basal lipolysis and TNF-alpha production when compared to normal rats. Perinodal mesenteric adipocytes present normal diameters, downregulated levels of PPAR-gamma-2, higher basal lipolysis and TNF-alpha, and leptin and adiponectin production. CONCLUSIONS: The findings suggest that mesenteric adipose tissue has a site-specific response during experimental inflammation, where perinodal adipose tissue retains the ability to produce different adipocytokines. These substances may interfere in many lymph node aspects, while mesenteric adipose tissue produces substances that could contribute directly to aggravate the inflammatory process.

Case 32. Eosinophilia: reactive or neoplastic?

A diagnosis of eosinophilic leukemia was suspected in a patient who presented with eosinophilia and a mild macrocytic anemia and was found to have trisomy 8. Further tests and the subsequent clinical course permitted an accurate diagnosis.

Case 34: acute leukemia in a patient with a previous history of breast cancer.

A 56-year-old woman presented with acute myeloid leukemia 3 years after presenting with carcinoma of the breast. Detailed investigations led to a precise diagnosis.