Predictive validity of current sarcopenia definitions (EWGSOP2, SDOC, and AWGS2) for clinical outcomes: A scoping review.

Over the last 3 years new definitions of sarcopenia by the Sarcopenia Definition and Outcome Consortium (2020, SDOC), European Working Group on Sarcopenia in Older People (2019, EWGSOP2) and Asian Working Group on Sarcopenia (2019, AWGS2) have been proposed. The objective of this scoping review was to explore predictive validity of these current sarcopenia definitions for clinical outcomes. We followed the PRISMA checklist for scoping reviews. Based on a systematic search performed by two independent reviewers of databases (Pubmed and Embase) articles comparing predictive validity of two or more sarcopenia definitions on prospective clinical outcomes published since January 2019 (the year these definitions were introduced) were included. Data were extracted and results collated by clinical outcomes and by sarcopenia definitions, respectively. Of 4493 articles screened, 11 studies (mean age of participants 77.6 (SD 5.7) years and 50.0% female) comprising 82 validity tests were included. Overall, validity tests on the following categories of clinical outcomes were performed: fracture (n = 40, assessed in one study), mortality (n = 18), function (n = 11), institutionalization (n = 7), falls (n = 4), and hospitalization (n = 2). Thereby, EWGSOP2 was investigated in 15 validity tests (18.3%) on all categories of clinical outcomes, whereas SDOC was investigated in four validity tests (4.9%) in one study on fractures in men only, and none of the validity tests investigated predictive validity by the AWGS2. However, we were not able to pool the data using a meta-analytic approach due to important methodological heterogeneity between the studies. We identified various definitions of clinical outcomes that were used to test predictive validity of sarcopenia definitions suggesting that an agreement on an operational definition of a clinical outcome is key to advance in the field of sarcopenia. Moreover, data on predictive validity using the sarcopenia definitions by the SDOC and AWGS2 are still scarce and lacking, respectively. In a next step, prospective studies including both women and men are needed to compare predictive validity of current sarcopenia definitions on defined key clinical outcomes.

Phagocytosis of cancer cells by mast cells in breast cancer.

BACKGROUND: Mast cells (MCs) remain enigmatic more than 100 years after their discovery by Paul Ehrlich. Continuous research over the last 20 years has finally characterized the origin of MCs and determined many of the factors involved in MC differentiation and proliferation. MCs are traditionally known for mediating allergic reactions. In addition, these cells have been implicated in the pathogenesis of clinical conditions. Studies on the role of MCs in cancer have given contrasting results. MATERIALS AND METHODS: This study included 50 cases of invasive ductal breast cancer not otherwise specified (NOS): 25 of them were highly hormone-receptive (HHR) cancers with estrogen and progesterone receptor values not lower than 50%, 25 were minimally hormone-receptive (MHR) cancers (<5%). In both groups, mast cells were quantified in the peritumoral area. Twenty cases of surgical interventions without cancer were included as controls. RESULTS: It was found that in infiltrating ductal breast cancers having a high hormone receptor content (>50% for both estrogen and progesterone), there was a highly significant increase in MCs with respect to hypo-hormonal cancers in the same location and to controls (p<0.0001). MCs have thus proven to be very important cells because they have been found in sites playing an active role in opposing the aggression of the cancer cells (CCs). MCs may represent a protective factor of the human body against cancer aggresion. Two biological phenomena with the same goal can be observed: CCs are first phagocytized by MCs and then completely destroyed by karyocytoplasmic chemolysis through the action of toxicophore granulations. It was demonstrated that one or more CCs are surrounded by an MC's pseudopodia and then engulfed in its cytoplasm. The phagocytized cell progressively loses its chromatic and volumetric characteristics until complete achromia and almost complete reduction of its volume and consistency occur. The cell nucleus soon degenerates to pyknosis and becomes no longer detectable.

Ultrastructural observations on inflammatory angiogenesis in gastric carcinomas with massive neutrophil infiltration.

Neutrophils are traditionally thought of as terminal effectors of inflammatory reaction, but experimental studies suggest that they play a direct role in the inflammatory angiogenesis of tumors. Thus, further evidence in humans is required regarding the mechanisms by which neutrophils induce tumor angiogenesis. In this study, 4 cases of human gastric carcinomas with massive neutrophil infiltration were studied by light and electron microscopy, focusing on the inflammatory angiogenesis in the tumor stroma. At light microscopy, the tumors were advanced gastric carcinomas in which various degrees of tubular differentiation were present. Under an electron microscope, pericytes exhibited two major differentiated states with distinct ultrastructural features: a contractile phenotype and a synthetic phenotype. The contractile phenotype was characterized by abundant microfilaments. Synthetic pericytes contained abundant rough endoplasmic reticulum, lipid bodies, and numerous membrane-bound vesicles. These ultrastructural findings extend concept of contractile/synthetic phenotype modulation, originally described in smooth muscle cells, to tumor microvascular pericytes. Tumor microvasculature was also characterized by abortive or slit-like lumina, endothelial cell mitoses, and replicating basement membranes. These qualitative and observational transmission electron microscopy findings provide additional morphological evidence of active inflammatory angiogenesis in gastric carcinomas with massive neutrophil infiltration.

Mast cells in invasive ductal breast cancer: different behavior in high and minimum hormone-receptive cancers.

BACKGROUND: Studies on the role of mast cells (MC) in cancer have given contrasting results. In order to contribute to the clarification of their role, research on breast cancer was carried out, because some aspects of its carcinogenesis, such as the diversity of the hormonal component, differ greatly. MATERIALS AND METHODS: This study included 50 cases of invasive ductal breast cancer not otherwise specified (NOS): 25 of them were high hormone-receptive (HHR) cancers with estrogen and progesterone receptor values not lower than 50%, 25 were minimum hormone-receptive (MHR) cancers (< 5%). In both groups, mast cells were quantified in the peritumoral area. Twenty cases of surgical interventions for non-neoplastic esthetic prosthesis in healthy women were examined as controls. The proliferation index Ki-67 (MIB1) and the c-erb B2 receptor protein were also considered in cancer patients. Mast cells were detected using Giemsa and Alcian blue stains. RESULTS: The results obtained showed that there was a highly significant increase in the number of mast cells mainly in the peritumoral area in HHR cancer cases (p < 0.0001) compared to MHR cancers and controls (p < 0.0001). Comparison between mast cells in MHR cancer and control cases was not significant (p = 0.114). Hormone-receptive cancers have a less severe prognosis for their higher responsiveness to therapy. This element may suggest that the higher mast cell number present in these types of cancer is a favorable prognostic factor. Moreover, mast cells tend to accumulate around the cancer area and this can be seen as an attempt to oppose the progression of the anomalous tissue. Mast cells were reported to exhibit cytolytic activity against tumor cells.

Vitamins A, E, microelements and membrane lipid peroxidation in patients with neoplastic disease treated with calcium antagonists and antagonists of receptors H2.

We studied the serum levels of vitamins A, E, zinc and copper in two hundred and twenty-five subjects of both sexes. They were divided into two groups: 87 healthy subjects who served as controls and 138 patients with neoplastic disease. The patients were subdivided according to the absence (n = 79) or the presence of metastatic disease (n =59). In 59 patients with cancer, who were in therapy with scavenger drugs of free radical such as calcium antagonists and the antagonists of receptors H2, we also studied the possible effect of the same therapy on the serum levels of vitamins, on the concentrations of the microelements and on membrane lipid peroxidation. We found that membrane lipid peroxidation, evaluated from the time of in vitro formation in the blood of so-called "Heinz bodies," decreased in all patients treated with scavenger drugs. In these patients the permeability of the erythrocyte membrane was similar to the controls and the serum levels of the vitamins were equal to the levels in patients who did not receive these therapies. Zinc concentration increased while copper remained unchanged. We also studied the levels of vitamins in some organs. The results are discussed considering the role of free radicals. We underline the importance of vitamins A and E in the protection from membranous peroxidation and from free radicals and the need to consider cancer as a systemic morbid event, apart from the contingent actual location.