Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial

Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab.     

Transcirculation Silk Vista Baby-assisted coiling in half-T configuration for the treatment of posterior communicating artery aneurysms associated with a fetal posterior circulation: An alternative flow diversion strategy

Flow diverter devices have become a routine first-line option for treatment of an increasing population of intracranial aneurysms at many neurovascular centers. Despite the promising results of flow diverter stents on anterior circulation, incomplete occlusion on the presence of fetal posterior circulation has been described on several reports. Here we describe a novel technical alternative to conventional flow diversion approach for this specific subgroup of aneurysms using the low-profile flow diverter, Silk Vista Baby. The device was selectively placed into the fetal type posterior cerebral artery in half-T configuration for the treatment of a posterior communicating aneurysm using a transcirculation approach through the anterior communicating artery. This represents a useful and effective technique and should be considered when encountering the above-described situation.     

Tenosynovial complications identify TTR cardiac amyloidosis among patients with hypertrophic cardiomyopathy phenotype

Recent evidence suggests that carpal tunnel syndrome (CTS) and brachial biceps tendon rupture (BBTR) represent red flags for ATTR cardiac amyloidosis (ATTR-CA). The prevalence of upper limb tenosynovial complications in conditions entering differential diagnosis with CA, such as HCM or Anderson–Fabry disease (AFD), and hence their predictive accuracy in this setting, still remains unresolved. Objective: To investigate the prevalence of CTS and BBTR in a consecutive cohort of ATTR-CA patients, compared with patients with HCM or AFD and with individuals without cardiac disease history. Participants: Consecutive patients with a diagnosis of ATTR-CA, HCM and AFD were evaluated. A control group of consecutive patients was recruited among subjects hospitalized for noncardiac reasons and no cardiac disease history. The presence of BBTR, CTS or prior surgery related to these conditions was ascertained. Results: 342 patients were prospectively enrolled, including 168 ATTR-CA (141 ATTRwt, 27 ATTRm), 81 with HCM/AFD (N = 72 and 9, respectively) and 93 controls. CTS was present in 75% ATTR-CA patients, compared with 13% and 10% of HCM/AFD and controls (P = 0.0001 for both comparisons). Bilateral CTS was present in 60% of ATTR-CA patients, while it was rare (2%) in the other groups. BBTR was present in 44% of ATTR-CA patients, 8% of controls and 1% in HCM/AFD. Conclusions: CTS and BBTR are fivefold more prevalent in ATTR-CA patients compared with cardiac patients with other hypertrophic phenotypes. Positive predictive accuracy for ATTR-CA is highest when involvement is bilateral. Upper limb assessment of patients with HCM phenotypes is a simple and effective way to raise suspicion of ATTR-CA.     

Adult-Onset Ligneous Conjunctivitis with Detection of a Novel Plasminogen Gene Mutation and Anti-Plasminogen IgA Antibody: A Clinicopathologic Study and Review of Literature

Purpose: To report a novel plasminogen gene mutation and detection of anti-plasminogen antibodies in a patient with ligneous conjunctivitis successfully treated with 60% fresh frozen plasma (FFP). Methods: Retrospective data collected on a 45-year-old Caucasian female presenting with unilateral chronic membranous lesions. Results: Laboratory investigation demonstrated decreased plasminogen antigen level, plasminogen activity, and rate of plasminogen activation by u-PA or t-PA, and elevated plasminogen activator inhibitor-1. Anti-plasminogen IgG and IgA antibodies were detected. DNA analysis revealed a novel Asp432Asn heterozygous missense mutation in the plasminogen gene (exon 11). The patient was treated with topical 60% FFP, achieved complete remission after four months, and remained membrane-free for over five years of follow-up. Conclusions: A novel plasminogen gene mutation, deficiency of plasminogen antigen and activity, and anti-plasminogen IgG and IgA antibodies were identified in a patient with adult-onset ligneous conjunctivitis. Sixty percent FFP maintained this patient disease-free for over five years.     

VGLUT‐VGAT expression delineates functionally specialised populations of vasopressin‐containing neurones including a glutamatergic perforant path‐projecting cell group to the hippocampus in rat and mouse brain

The origin and functional significance of vasopressin (AVP)‐containing fibres in limbic regions has been an ongoing subject of investigation for several years. We have previously identified AVP‐magnocellular neurones of rat hypothalamus that provide glutamatergic projections to the hippocampus, amygdala, lateral habenula and locus coeruleus. However, we also reported AVP‐immunopositive fibres in those regions that are thin and make Gray type II synapses, which are unlikely to be of magnocellular origin. Therefore, in the present study, we characterised AVP mRNA co‐expression with expression of mRNAs marking glutamatergic (vesicular glutamate transporter [VGLUT]) and GABAergic (vesicular GABA transporter [VGAT]) neuronal traits in rat and mouse brain, using high‐resolution in situ hybridisation methods, including a radio‐ribonucleotide and RNAscope 2.5 HD duplex assay, with Slc17a7, Slc17a6, Slc32a1 and Avp probes corresponding to mRNAs of VGLUT1, VGLUT2, VGAT and AVP, respectively. We located 18 cell groups expressing Avp and identified their molecular signatures for VGLUT and VGAT mRNA expression. Avp cell groups of hypothalamus and midbrain are mainly VGLUT mRNA‐expressing, whereas those in regions derived from cerebral nuclei are mainly VGAT mRNA‐expressing, suggesting a functional segregation of glutamate/GABA co‐transmission with AVP. A newly identified Slc17a7 and Slc17a6 (but not Slc32a1) expressing vasopressinergic cell group was found in layer II‐III neurones of the central entorhinal cortex, which projects to the hippocampus. These data support the notion of a complex role for AVP with respect to modulating multiple central circuits controlling behaviour in specific ways depending on co‐transmission with glutamate or GABA, potentially giving rise to a functional classification of AVPergic neurones in the central nervous system.     

Fertility-sparing surgery for patients with malignant ovarian germ cell tumors: 10 years of clinical experience from a tertiary referral center

Archives of Gynecology and Obstetrics - To describe a case series of patients with malignant ovarian germ cell tumors (MOGCT) treated exclusively with fertility-sparing surgery (FSS) with or...