The relevance of occult axillary micrometastasis in ductal carcinoma in situ

Abstract

Electrospray ionization (ESI) of tetrameric platinum(II) acetate, [Pt4(CH3COO)8], in methanol generates the formal platinum(III) dimeric cation [Pt2(CH3COO)3(CH2COO)(MeOH)2]+, which, upon harsher ionization conditions, sequentially loses the two methanol ligands, CO2, and CH2COO to form the platinum(II) dimer [Pt2(CH3COO)2(CH3)]+. Next, intramolecular sequential double hydrogen‐atom transfer from the methyl group concomitant with the elimination of two acetic acid molecules produces Pt2CH+ from which, upon even harsher conditions, PtCH+ is eventually generated. This degradation sequence is supported by collision‐induced dissociation (CID) experiments, extensive isotope‐labeling studies, and DFT calculations. Both PtCH+ and Pt2CH+ react under thermal conditions with the hydrocarbons C2Hn (n=2, 4, 6) and C3Hn (n=6, 8). While, in ion–molecule reactions of PtCH+ with C2 hydrocarbons, the relative rates decrease with increasing n, the opposite trend holds true for Pt2CH+. The Pt2CH+ cluster only sluggishly reacts with C2H2, but with C2H4 and C2H6 dihydrogen loss dominates. The reactions with the latter two substrates were preceded by a complete exchange of all of the hydrogen atoms present in the adduct complex. The PtCH+ ion is much less selective. In the reactions with C2H2 and C2H4, elimination of H2 occurs; however, CH4 formation prevails in the decomposition of the adduct complex that is formed with C2H6. In the reaction with C2H2, in addition to H2 loss, C3H3+ is produced, and this process formally corresponds to the transfer of the cationic methylidyne unit CH+ to C2H2, accompanied by the release of neutral Pt. In the ion–molecule reactions with the C3 hydrocarbons C3H6 and C3H8, dihydrogen loss occurs with high selectivity for Pt2CH+, but in the reactions of these substrates with PtCH+ several reaction routes compete. Finally, in the ion–molecule reactions with ammonia, both platinum complexes give rise to proton transfer to produce NH4+; however, only the encounter complex generated with PtCH+ undergoes efficient dehydrogenation of the substrate, and the rather minor formation of CNH4+ indicates that CN bond coupling is inefficient.

The clinical significance of sentinel lymph node micrometastasis in breast cancer

“…In another study of 102 patients with DCIS and negative axillary nodes, MM were identified in 13% on retrospective analysis. After 10-28 years of follow-up, the overall disease recurrence rate was 12% although none of these patients had been found to harbour MM and the recurrence site was not found to be the axilla in any case [67]. The low rate of local recurrence and excellent overall survival in these patients has been suggested to provide further circumstantial evidence against the significance of MM.…”

Meta-analysis of sentinel node biopsy in ductal carcinomain situof the breast

“…Another aspect of the argument against performing SLN biopsy in patients with a presumed diagnosis of DCIS is the problem of a positive SLN in this setting. The management of such patients is controversial as metastatic involvement of the SLN is frequently in the form of micrometastases (defined as small metastases no larger than 2 mm but larger than 0·2 mm) detected using immunohistochemistry alone 21,29,30,57 . The prognostic significance and clinical consequences of micrometastases in the SLN even in invasive breast cancer remain matters of debate.…”

Sentinel lymph node biopsy in clinically detected ductal carcinomain situ

“…The incidence and clinical significance of nodal meta stasis in DCIS has been evaluated in both the pre-and the post-screening era. In the pre-screening era, ALND was not performed in DCIS because of the low incidence of axillary metastasis (1%-2%), and the high morbidity associated with ALND [12,13] . This low rate of axillary lymph node involvement in pure DCIS was attributed to missed diagnosis of invasion in the final pathology of the breast specimen [2,12] .…”