Prospective study: Impact of breast magnetic resonance imaging on oncoplastic surgery and on indications of mastectomy in patients who were previously candidates to breast conserving surgery.

Background: Routine use of magnetic resonance imaging (MRI) in the staging of patients with early breast cancer is still controversial. Oncoplastic surgery (OP) allows for wider resections without compromising the aesthetic results. This study aimed to assess the impact of preoperative MRI on surgical planning and on indications of mastectomy. Methods: Prospective study including T1-T2 breast cancer patients treated between January 2019 and December 2020 in the Breast Unit of the Hospital Nossa Senhora das Graças in Curitiba, Brazil. All patients had indication for breast conserving surgery (BCS) with OP and did a breast MRI after conventional imaging. Results: 131 patients were selected. Indication for BCS was based on clinical examination and conventional imaging (mammography and ultrasound) findings. After undergoing breast MRI, 110 patients (84.0%) underwent BCS with OP and 21 (16.0%) had their surgical procedure changed to mastectomy. Breast MRI revealed additional findings in 52 of 131 patients (38%). Of these additional findings, 47 (90.4%) were confirmed as invasive carcinoma. Of the 21 patients who underwent mastectomies, the mean tumor size was 2.9 cm (± 1,7cm), with all having additional findings on breast MRI (100% of the mastectomies group vs 28.2% of the OP, p<0.01). Of the 110 patients submitted to OP, the mean tumor size was 1,6cm (± 0,8cm), with only 6 (5.4%) presenting positive margins at the final pathology assessment. Conclusion: Preoperative breast MRI has an impact on the OP scenario, bringing additional information that may help surgical planning. It allowed selecting the group with additional tumor foci or greater extension to convert to mastectomy, with a consequent low reoperation rate of 5.4% in the BCS group. This is the first study to assess the impact of breast MRI in the preoperative planning of patients undergoing OP for the treatment of breast cancer.

Câncer de mama oculto em homem com metástase para tecido celular subcutâneo axilar: relato de caso / Occult breast cancer in man with axillary subcutaneous tissue metastasis: case report

O câncer oculto de mama, que representa menos de 1% de todos os casos de câncer de mama, é definido como doença não identificada durante o exame físico do paciente nem por exames de imagem da mama, mas que apresenta linfadenopatia axilar compatível para câncer por meio de exames imuno-histoquímicos. Apenas 1% dos casos de câncer de mama acomete indivíduos do sexo masculino. Além disso, representa menos de 1% de todos os cânceres em homens, e tal o câncer representa menos de 1% de todos os cânceres em homens. Apresentou-se o caso de um homem de 54 anos com câncer de mama oculto apresentando metástase para tecido subcutâneo axilar, apresentado como nódulo em topografia axilar esquerda. Após a exérese da lesão, o paciente foi submetido à adenomastectomia bilateral e linfadenectomia axilar à esquerda, sendo o exame anatomopatológico das peças negativo para neoplasia. O paciente realizou radioterapia complementar e encontra-se em hormonioterapia com tamoxifeno (cinco anos). No momento, encontra-se em seguimento sem evidência de doença em atividade. Concluiu-se que o câncer de mama oculto em homem é raro e, por isso, ainda existem divergências sobre o tratamento definitivo, não devendo nunca se subestimar queixas mamárias.

Occult breast cancer, which represents less than 1% of all the cases of breast cancer, is defined as axillary metastasis without clinically and/or radiologically evident primary tumor, but the axillary metastasis is compatible with cancer through immunohistochemistry examinations. Only 1% of the cases of breast cancer occurs in men, and breast cancer accounts for less than 1% of all cancers in men. The authors presented a case study of a 54 year old man with occult breast cancer presenting axillary metastasis to subcutaneous tissue in the left axillary node topography. After excision, the patient underwent bilateral adenomastectomy and left axillary lymphadenectomy, with the pathologic diagnosis negative for any trace of malignancy. The patient underwent radiotherapy and is on hormone therapy with tamoxifen for five years. At the moment, he lies in tracking without evidence of active disease. It was concluded that occult breast cancer is rare in men and, due to that, there are still disagreements over the definitive treatment that can be done to this disease. Another important point is that breast complaints should never be underestimate in male patients.

Selective inhibition of Human Immunodeficiency Virus type 1 (HIV-1) by a novel family of tricyclic nucleosides.

Nucleoside 1, with an unusual tricyclic carbohydrate moiety, specifically inhibits HIV-1 replication while being inactive against HIV-2 or other (retro) viruses. In an attempt to increase the inhibitory efficacy against HIV-1, and to further explore the structural features required for anti-HIV-1 activity, different types of modifications have been carried out on this prototype compound. These include substitution of the ethoxy group at the C-4″ position by alkoxy groups of different length, branching, conformational freedom or functionalization. In addition, the 4″-ethoxy group has been removed or substituted by other functional groups. The role of the tert-butyldimethylsilyl (TBDMS) group at the 2' position has also been studied by preparing the corresponding 2'-deprotected derivative or by replacing it by other silyl (tert-hexyldimethylsilyl) or acyl (acetyl) moieties. Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl. Some of these compounds were endowed with a 6- to 7-fold higher selectivity than the prototype 1. The tricyclic nucleosides here described represent a novel type of selective anti HIV-1 inhibitors, targeted at the HIV-1-encoded reverse transcriptase.

Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators.

Searching for a novel family of inactivators of the human DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) which is known to bind to the DNA minor groove, we have computationally modelled and synthesised two series of 2-amino-6-aryloxy-5-nitropyrimidines with morpholino or aminodiaryl substituents (potential minor groove binders) at the 4-position. Synthesis of these compounds was achieved by successive substitution of each of the two Cl atoms of 2-amino-4,6-dichloro-5-nitropyrimidine by the corresponding amino and aryloxy derivatives. Biochemical evaluation of these compounds as MGMT inactivators showed poor activities, but in general the 4-bromothenyloxy derivatives showed better inactivation than the benzyloxy versions. DNA binding assessment was not possible due to insolubility problems.

One-pot synthesis of polycyclic nucleosides with unusual molecular skeletons.

An alpha hydroxy pyrrolidine tricyclic nucleoside 3 and its spontaneous reaction with acetone is described. In this transformation highly functionalized polycyclic nucleosides with rather unusual molecular skeletons are formed in a complete regio- and stereoselective way. The reaction involves the formation of three new bonds, two of them novel carbon-carbon bonds, in a one-pot way. An enamine-iminium mechanism with participation of carbinolamine, iminium ion, and enamine intermediates is proposed as a plausible explanation for this transformation. The scope of the reaction is briefly studied concluding that the nature of the ketone (R(1)COR(2)) is critical for the initial attack of the NH to the carbonyl group.

Synthesis of highly condensed polycyclic carbohydrates by reaction of a spirocyclic enamino sulfonate derived from d-xylofuranose with bifunctional reagents.

The appropriately substituted 5-O-tosyl derivative (1), easily prepared from 1,2-O-isopropylidene-alpha-d-xylofuranose, serves as a useful precursor for the preparation of highly condensed cyclic carbohydrates. The synthesis involves a first cyclization of the 5-O-tosyl sugar derivative 1 to a highly reactive cyclic enamine, which subsequently undergoes the nucleophilic attack of a bifunctional reagent X(CH2)nZ in a regio- and stereospecific way. Finally, a spontaneous cyclization step allows the formation of a stereochemically defined extra ring, fused to the sugar backbone. The functionalization and size of this ring can be varied by the proper choice of the bifunctional reagent. X-ray diffraction analysis and intensive NMR studies with one of these carbohydrates were performed to highlight the strained nature of these compounds.

A cyclic enamine derived from 1,2-O-isopropylidene-alpha-D-xylofuranose as a novel carbohydrate intermediate to achieve skeletal diversity.

The commercially available carbohydrate 1,2-O-isopropylidene-alpha-D-xylofuranose was efficiently transformed into the high-added-value synthetic scaffold 8. The transformation requires the synthesis of the 5-O-tosyl derivative 7 and its subsequent intramolecular cyclization under basic conditions to give the cyclic enamine 8. Reaction of 8 with O-, N-, S-, and C-nucleophiles and amino acids allowed its efficient transformation (one-step, high yields, and easy purifications) into fused cyclic sugar derivatives with rather unusual molecular skeletons in a completely regio- and stereoselective manner. The characteristics of the sugar derivative 8 established here, high reactivity, synthetic accessibility, and the potential for conversion into a vast collection of products by the action of different nucleophiles, indicate that it will prove to be a useful chiral intermediate for achieving skeletal diversity. The constrained structures and dense functionalization of the polycyclic sugar derivatives generated from 8 make these compounds promising candidates for use as starting agents for the production of new analogues and as drugs.

Novel [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2" -dioxide) derivatives with anti-HIV-1 and anti-human-cytomegalovirus activity.

New [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-d-ribofuranosyl]-3'-spiro-5' '-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives substituted at the 4' '-amino group of the spiro moiety with different carbonyl functionalities have been designed and synthesized. Various synthetic procedures, on the scarcely studied reactivity of the 3'-spiroaminooxathioledioxide moiety, have been explored. The compounds were evaluated for their inhibitory effect on both wild-type and TSAO-resistant HIV-1 strains, in cell culture. The presence of a methyl ester (10) or amide groups (12) at the 4''-position conferred the highest anti-HIV-1 activity, while the free oxalyl acid derivative (11) was 10- to 20-fold less active against the virus. In contrast, the presence at this position of (un)substituted ureido or acyl groups markedly diminished or annihilated the anti-HIV-1 activity. Surprisingly, some of the target compounds also showed inhibition of human cytomegalovirus (HCMV) replication at subtoxic concentrations. This has never been observed previously for TSAO derivatives. In particular, compound 26 represents the first TSAO derivative with dual anti-HIV-1 and -HCMV activity.

Synthesis of novel Bi-, Tri-, and tetracyclic nucleosides by reaction of a common cyclic enamine derived from TSAO-T with nucleophiles.

We report here the efficient regio- and stereoselective synthesis of new polycyclic nucleosides using a common cyclic enamine (7) as the starting material. In fact, the reaction of 7, easily prepared by reaction of 5'-O-Tosyl TSAO-T under basic nonnucleophilic conditions (potassium carbonate), with different classes of nucleophiles, for example, nitrogen-, oxygen-, sulfur-, and carbon-based nucleophiles, or with amino acids afforded, with total regio- and stereoselectivity, new bi-, tri-, and tetracyclic nucleosides. This straighforward route represents an original and unambiguously regio- and stereoselective pathway to these compounds. Some of these polycyclic nucleosides may be useful intermediates for a second series of reactions that may lead to the generation of structurally new nucleosides.