Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy : Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical)

Purification of frog (Rana ridibunda) thyrotropin and its identification using a specific and sensitive bioassay

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Effects of TRH, bovine TSH, and pituitary extracts on thyroidal T4 release in Ambystoma mexicanum

Circulating levels of T4 are measured by radioimmunoassay after intravenous injection of TRH, bovine (b) TSH, and pituitary extracts in the Mexican axolotl (Ambystoma mexicanum). Very low control levels of T4 are found (53 ± 3 pg/ml (n = 27), but they are increased sevenfold following injection of 1/2 pars distalis extract or 1/2–1/10 IU b-TSH. Increased levels following these injections are found in plasma up to 48 hr after the injection. An in vitro assay also indicates that a 1/2 pars distalis of the axolotl is able to release T4 from the thyroid of R. ridibunda somewhat less effectively than a 1/50 pars distalis of the same size of R. ridibunda itself. TRH (50 and 100 μg) is unable to stimulate the release of T4 when injected intravenously into the axolotl. It is concluded that both the hypophysis and the thyroid gland of A. mexicanum may release optimal amounts of hormones necessary for metamorphosis following proper stimulation, but that TRH cannot function as a releasing hormone in this respect.status: publishe

Increased Plasma Levels of Thyroid Hormones in a Frog Rana ridibunda Following Intravenous Administration of TRH

The vena abdominalis of pentobarbital anesthetized frogs (Rana ridibunda) was cannulated for injection and blood sampling. After acetone and petroleum ether extraction, serum was concentrated 4 and 20 times and T3 and T4 were determined by radioimmunoassay. In 8 frogs, an injection of 10 μg synthetic TRH (pGlu-His-ProNH2) increased control levels of 0.35 ± 0.08 ng T4/ml after 1, 2, 4, and 8 hr, with a maximal increase up to 2.65 ± 0.48 ng/ml after 4 hr. In 7 frogs, 1 μg TRH raised control levels of 0.52 ± 0.22 ng/ml after 1, 2, and 4 hr, with a peak value of 1.74 ± 0.45 ng/ml after 2 hr. Control injections (Ringer), 0.01 and 0.1 μg TRH were without effect. Control levels of T3 (0.029 ± 0.005 ng/ml) were also raised after 4 hr (0.051 ± 0.007 ng/ml) in 7 animals, but only with the 10-μg TRH dose. Two days after removal of the pars distalis, circulating levels of T4 (but not T3) in frog serum were significantly depressed, whereas T3 and T4 content of thyroids remained unchanged. An intravenous injection of 10 μg TRH did not alter circulating levels of T3 and T4. These results indicate that the activity of the thyroid gland of R. ridibunda is stimulated by intravenous injections of TRH and that this effect is mediated through the hypophysis.status: publishe

Difference of the in vivo responsiveness to thyrotropin stimulation between the neotenic and metamorphosed axolotl, Ambystoma mexicanum : Failure of prolactin to block the thyrotropin-induced thyroxine release

Basal and TSH-induced plasma concentrations of T4 have been measured by radioimmunoassay in the neotenic and metamorphosed male axolotl Ambystoma mexicanum both before and after an ovine prolactin pretreatment. All injections are made into the vena abdominalis. Basal levels of T4 are low in neotenes (85 ± 19 pg/ml) and somewhat higher in metamorphosed Ambystoma (171 ± 39 pg/ml), but are increased during metamorphosis (1094 ± 138 pg/ml). Following injection of 5 mU bovine TSH circulating levels of T4 are raised about 4 times in neotenes, but more than 50 times in metamorphosed animals. Three intravenous injections, each of 640 mU prolactin and given, respectively, 24 and 13 hr before and simultaneously with 5 mU TSH, do not inhibit the TSH-induced release in both experimental groups. In the metamorphosed Ambystoma again a more than 50-fold T4 increase is present, whereas in neotenes a 10-fold TSH-induced T4 release is seen, which is more pronounced than before the prolactin treatment. It is concluded that in A. mexicanum ovine prolactin does not block a TSH-induced T4 release and that any antagonistic action with thyroid hormones is not mediated through the thyroid gland.status: publishe

Fetal growth inhibition and decreased thyroid activity after injection of oestradiol benzoate into pregnant rats

Pregnant rats were subcutaneously injected daily with 10 μg oestradiol benzoate (OB) and/or 1 mg bromocriptine starting on day 15 of gestation. After treatment with OB, but not bromocriptine, lower fetal body weight, fetal length and placental weight were observed. The administration of bromocriptine did not influence maternal plasma levels of prolactin, but fetal levels were decreased on day 22 of gestation. Oestradiol benzoate raised prolactin concentrations in maternal plasma on days 20 and 22, whereas fetal plasma levels were raised on day 22. This increase was counteracted by simultaneous administration of bromocriptine and OB, whereas impairment of fetal growth remained after treatment. A slight decline in fetal plasma levels of insulin was observed once, but thyroid content of triiodothyronine and thyroxine (T4) was decreased to a quarter and a third respectively of control levels in male and female fetuses of OB-treated rats, fetal circulating levels of T4 were also depressed. Maternal and fetal plasma glucose levels were decreased. A close correlation between T4 and placental or fetal weight was always present on day 22 of gestation. It was concluded that OB injected into pregnant rats will reach the fetal circulation as judged by increases in fetal plasma levels of prolactin. The observed fetal growth retardation after the OB injection was associated with thyroid deficiency, whereas plasma levels of prolactin and insulin were either not at all or only slightly altered. A direct effect of OB on placental blood flow and hence on the fetal food supply cannot, however, be excluded.status: publishe

Control strategies of thyroid hormone monodeiodination in vertebrates

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Purification of tilapia thyrotropin from a crude pituitary homogenate by immunoaffinity chromatography using a matrix of antibodies against porcine follicle stimulating hormone

An immunoadsorbent matrix using antibodies against porcine follicle-stimulating hormone (pFSH), a high heterothyrotropic stimulant in tilapia, was used to purify tilapia thyrotropic hormone (t-TSH) from crude pituitary extracts. A homologous bioassay monitored TSH bioactivity during the purification. Thyroid hormones (thyroxine, T4; triiodothyronine, T3; and reverse triiodothyronine, rT3) and testosterone were measured in vivo in Tilapia nilotica. TSH activity eluted as one major peak at pH 2.8 using a PBS-glycine buffer. The TSH fraction increased plasma T4 and plasma rT3. The potency of tTSH was comparable to that of pituitary extract or its Con A II fraction; however, pFSH was a stronger thyroid stimulant. tTSH had no effect on plasma T3 levels and was free of gonadotropic activity, as indicated by its failure to alter plasma testosterone concentrations. Chromatographic and electrophoretic analyses demonstrated a high degree of purity. Like other vertebrate TSHs, the tTSH appeared to have a subunit structure with a possible microgeneity in one subunit.status: publishe

Growth of heat-shock induced triploids of blue tilapia, Oreochromis aureus, reared in tanks and in ponds in Eastern Congo: feeding regimes and compensatory growth response of triploid females

In this study, triploids of Oreochromis aureus were obtained via the heat-shocking method. Triploid fishes were effectively sterile and predominantly female (80%). Diploid and triploid fishes were reared in tanks or ponds receiving organic manure. In tanks, the survival rate was 65.3% and 60.7% for diploids and triploids, respectively. Triploids, mostly females, grew slower (P < 0.05) than diploids consisting of almost equal number of females and males. In ponds, a significant difference in body weight (P < 0.05) in favour of diploids was also recorded, but both lines grew slower than in tanks. In another tank trial, growth of diploid and triploid females was compared using a normal feeding regime (7 days/week of feeding) or a restricted feeding regime (5 days/week of feeding). A little difference in growth was recorded in favour of triploids under the normal feeding regime. However, a high significant difference (P < 0.001) between diploids (71.8 +/- 5.8 g) and triploids (118.5 +/- 8.9 g) was recorded under the restricted feeding regime. While the diploids under the restricted feeding regime grew slower than diploids under the normal feeding regime, no difference in growth between triploids in the normal and restricted feeding regime was observed. (C) 2001 Elsevier Science B.V. All rights reserved.status: publishe