Dysgeusia increases the risk for death and other side effects during antineoplastic systemic treatment for solid tumors: a cross-sectional study.

BACKGROUND: Chemotherapy (QT) is a systemic treatment using a combination of antineoplastic drugs, orally or intravenously, that inhibit tumor growth and fast-growing normal cells. Due to its nonspecificity, chemotherapy can cause a series of adverse effects, such as altered taste (dysgeusia), associated with malnutrition and, consequently, other adverse effects in the gastrointestinal tract and increased mortality risk. This study aimed to evaluate the influence of dysgeusia on the incidence of other adverse effects and overall survival during antineoplastic chemotherapy (chemotherapy). MATERIAL AND METHODS: An observational, retrospective, cross-sectional study was conducted using data from the Electronic Health Record system of the Cancer Institute of Ceará over two years. Before the CT session, the multi-professional team evaluated the patient for the presence and severity of adverse effects (AE), using scores from the CTCAE v5.0 scale. Dysgeusia scores were collected and associated with clinical pathological data, with other adverse effects (nausea, vomiting, diarrhea, oral mucositis, anorexia, constipation), and with overall survival. Chi-square and Mantel-Cox log-rank tests were used. RESULTS: Of 5744 patients evaluated, dysgeusia presented a frequency of 50.6%, being directly associated with female gender (p=0.001), overweight (p=0.022), high tumor stages (p=0.009), a combination of adjuvant and neoadjuvant (p=0.010) and four-year survival (p=0.030). Dysgeusia frequency was directly associated with diarrhea (p<0.001), anorexia (p<0.001), oral mucositis (p<0.001), nausea (p<0.001), constipation (p<0.001) and vomiting (p<0.001), and inversely associated with fatigue (p=0.035). CONCLUSIONS: Dysgeusia during CT increases the risk of other adverse effects and negatively impacts prognosis.

Tumor cell dissemination patterns and metastasis of murine mammary carcinoma.

Quantitative studies on the distribution kinetics of isotope-labeled cells from spontaneous murine mammary tumors injected intravenously or arterially showed that cells were rapidly distributed to all organs examined and indicated that the distribution patterns of metastases from such tumors are not primarily determined by the dose of cells delivered to each organ. The preferential colonization of certain organs is therefore considered to depend as much on differential survival and growth of the disseminated tumor cells in unfamiliar metabolic microenvironments, as on vascular sieving effects in organ capillary networks. Further experiments involved transplantation of pieces of nonpulmonary tissue containing trapped mammary tumor cells into syngeneic mice, followed by observation of the animals for several months. From these studies it is concluded that the absence of tumor colonies in extrapulmonary sites after i.v. inoculation is due to their inability to thrive in the organs concerned and not to early death of the original host from heavy pulmonary tumor growth. These results provide further evidence strengthening the conclusion emerging from several independent lines of investigation (Potter et al., Invasion Metastasis, 3: 221-233, 1983; Tarin et al., Cancer Res., 41: 3604-3609, 1981; Tarin et al., Cancer Res., 44: 3584-3592, 1984; Horak et al., J. Natl. Cancer Inst., 76: 913-922, 1986; Nicolson et al., Int. J. Cancer, 38: 289-294, 1986; Naito et al., Invasion Metastasis, 7: 16-29, 1987) that the growth of disseminated tumor cells is inhibited or even abrogated by many of the organs in which the cells sequester after vascular dissemination.

Vascular dissemination of tumor cells in relation to temperature-dependent metastasis in frogs.

Metastasis is a temperature-related phenomenon in the North American leopard frog (Rana pipiens) affected with the Lucké renal adenocarcinoma. The frog is a poikilothermic vertebrate whose internal body temperature closely follows that of the environment, and tumor-bearing frogs living in a warm (28 degrees C) environment have a much higher incidence of metastasis (greater than 75%) than those in cold (4 degrees C) conditions (less than 6%). In this investigation it was found that Lucké tumor cells labeled with fluorescein isothiocyanate could be detected in frozen sections of all organs examined within 15 minutes, regardless of whether the hosts were adapted to a warm or a cold environment. Separate experiments involving inoculation of isotope-labeled tumor cells demonstrated that large numbers of cells arrived in the liver and other organs of animals kept at either end of the temperature range. These findings show that the infrequency of metastasis by Lucké adenocarcinomas in chilled frogs is not due to failure of dissemination of tumor cells consequent upon temperature-mediated changes in blood viscosity or flow patterns. Thus they establish the important baseline that the effects of temperature on metastasis in this vertebrate are exerted directly on the tumor cells and/or the internal environment of the host and that the system therefore provides new opportunities for probing the biology and biochemistry of tumor metastasis.

Collagenase secretion by human breast neoplasms: a clinicopathologic investigation.

Evidence is presented that biopsy specimens from fibroadenomas, benign cystic lesions, and carcinomas of the human breast can produce in organ culture a neutral protease capable of digesting type I collagen. This enzyme activity, measured with the use of a radioactive release assay, was characterized as true vertebrate collagenase and occurred in both active and latent (requiring trypsin activation) forms. For the two types of benign breast lesion studied, collagenase secretion was significantly higher from fibroadenomas than from benign cystic tissue. Breast carcinomas, however, exhibited a wide quantitative spectrum of collagenase secretion, encompassing the extremes observed for the benign lesions and showing no correlation with histologic type. These results, while providing a plausible mechanism for the marked collagen degradation seen in disseminating neoplasms, demonstrate that high collagenase secretory activity is not pathognomonic of invasive behavior. The findings, however, indicate disordered regulation of collagenase activity in malignant tumors.

Observations on organ distribution of fluorescein-labelled tumour cells released intravascularly.

By labelling cells with fluorescein isothiocyanate (FITC) and other fluorescent dyes and examining frozen sections of several organs of the recipients with an ultraviolet microscope, it has been demonstrated that viable tumour cells arrive in all organs examined within 15 min of inoculation either intravenously or arterially and are still detectable in various organs 30 days later. Although the method is not quantitatively accurate, its advantages are that the cells can be directly visualised and it can be confirmed that the label is attached to whole viable cells and not to cellular fragments. The findings effectively dispose of the possibility that the consistent absence of deposits in certain sites in animals inoculated with cells from spontaneous murine mammary tumours is due to failure of the cells to reach them. It has also been confirmed that FITC-labelled cells are still capable of forming deposits and occasional fluorescent cells are detected in these secondary neoplasms.

Organ preferences in metastatic colony formation by spontaneous mammary carcinomas after intra-arterial inoculation.

We have demonstrated earlier that cells from some spontaneous murine mammary tumours heavily colonise the lungs of every inoculated animal when injected intravenously, whereas those from others do so weakly or not at all. Extrapulmonary deposits are rare when cells are inoculated by this route. In the current experiments, we have found that if the cells are inoculated retrograde along the subclavian artery into the arch of the aorta, or directly into the abdominal aorta, they are capable of colonising organs other than the lungs and that individual tumours have reproducible preferences for establishing colonies in certain sites. The combination of organs favoured vary from tumour to tumour but most still showed a predilection for forming pulmonary deposits. Several organs are not colonised by any tumour in any recipient. It is concluded that the distribution of metastatic colonies formed by these spontaneous mammary tumours is influenced by interplay between intrinsic properties of tumour cells, microenvironmental influences in the organs in which the cells arrest, and rheological considerations.