Predicting Nipple–Areolar Involvement Using Preoperative Breast MRI and Primary Tumor Characteristics

Background

Preoperative assessment of the nipple–areolar complex (NAC) is invaluable when considering nipple-sparing mastectomy. Our hypothesis is that breast magnetic resonance imaging (MRI) may predict involvement of the NAC with tumor.

Methods

Clinical, histopathologic, and imaging data were compiled for patients who underwent preoperative breast MRI followed by mastectomy or nipple-sparing mastectomy for malignancy between 2006 and 2009. Blinded rereview of all MRI studies was performed by a breast MRI imager and compared to initial MRI findings. Multivariate analysis identified variables predicting NAC involvement with tumor.

Results

Of 77 breasts, 18 (23 %) had tumor involving or within 1 cm of the NAC. The sensitivity of detecting histopathologically confirmed NAC involvement was 61 % with history and/or physical examination, and 56 % with MRI. Univariate analysis identified the following variables as significant for NAC involvement: large tumors near the nipple on preoperative MRI, node-positive disease, invasive lobular carcinoma, advanced histopathologic T stage, and neoadjuvant chemotherapy. On multivariate analysis, only tumor size >2 cm and distance from tumor edge to the NAC <2 cm on MRI maintained significance. Pearson correlation coefficient for MRI size compared to histopathologic size was 0.53 (P < 0.0001).

Conclusions

MRI is not superior to thorough clinical evaluation for predicting tumor in or near the NAC. However, MRI-measured tumor size and distance from the NAC are correlated with increased risk of NAC involvement. The combination of preoperative history and physical examination, tumor characteristics, and breast MRI can aid the surgeon in predicting a tumor-involved nipple more than any single modality alone.     

Evidence for a Better Nodal Staging System for Melanoma: The Clinical Relevance of Metastatic Disease Confined to the Sentinel Lymph Nodes

Background

The hypothesis tested in this study was whether patients with stage III metastatic melanoma confined to their sentinel lymph nodes (SLNs) had a more favorable prognosis than patients who had SLN and non-SLN (NSLN) metastases.

Methods

Patients were identified who were clinically negative in their regional basins but with lymphatic mapping were found to have positive SLNs (331 patients). All patients subsequently underwent a complete lymph node dissection of the lymphatic basin involved, and the total number of metastatic SLNs and NSLNs were documented.

Results

As the regional metastatic disease involves NSLNs, disease-free survival (DFS) and overall survival (OS) decreases. For patients with a total of 2 nodes positive, those with disease confined to the SLNs had a significant better prognosis (DFS and OS: P < .00001) than those in whom 1 SLN and 1 non-SLN was involved. This difference was apparent for those patients with N2 and N3 disease (2 or more nodes positive in their regional basin). A multivariate regression analysis that included Breslow thickness, ulceration, number of positive nodes, and NSLN positivity showed that NSLN positivity (P = .0019) was the most powerful predictor of DFS and OS.

Conclusions

When metastatic melanoma overwhelms the SLN and involves NSLNs, the biologic behavior changes to portend a worse survival, regardless of the total node count positive. These data make the argument that the current N staging system should be changed to incorporate SLN vs NSLN involvement.     

Penetrating Aortic Ulcer and Intramural Hematoma

CardioVascular and Interventional Radiology - Acute aortic syndromes include a variety of overlapping clinical and anatomic diseases. Penetrating aortic ulcer (PAU), intramural hematoma (IMH) and...     

Pharmacokinetic drug evaluation of dolutegravir plus rilpivirine for the treatment of HIV

Introduction: The search for simple, potent, metabolic-friendly and nucleoside/nucleotide sparing antiretroviral regimens has led clinical investigators to move steps towards dual therapies. Among these the association of rilpivirine and dolutegravir is emerging as a twin randomized clinical trial (SWORD1&2) and at least three observational cohort describe it as a safe and highly effective regimen for switch from other therapies

Areas covered: We review the evidence supporting the use of dolutegravir plus rilpivirine for the treatment of HIV in virologically suppressed patients taking other antiretroviral regimens. The reasons for the switch in clinical practice may range from simplification to tolerability/toxicity issues, to the prevention of future metabolic damage, to predicted drug-drug interactions when treatment of HCV co-infection is planned. Articles searchable on MEDLINE/PubMed and from the main international congresses in the field of HIV therapy were reviewed to provide context for use of dolutegravir plus rilpivirine

Expert opinion: This treatment is highly effective in maintaining HIV-1 RNA <50 copies/mL. Although the studies up to date requested patient to switch to drugs they had no experience of, a predictable ‘radical change’ effect did not impact negatively on the results. Further data from these studies may help elucidate the possible advantage in terms of safety and metabolic effect in the next few months.     

Ejaculation induced by i.c.v. injection of the preferential dopamine D(3) receptor agonist 7-hydroxy-2-(di-N-propylamino)tetralin in anesthetized rats

In addition to serotonin, dopamine within the CNS is known to play a primary role in the control of ejaculation. However, whether D(2) and/or D(3) dopamine receptor subtypes mediate this effect is still unclear. In order to clarify this issue, a pharmacological competitive study using the preferential D(3) agonist 7-hydroxy-2-(di-N-propylamino)tetralin (7-OH-DPAT) alone or in combination with competitive nonpreferential or preferential D(2) and D(3) antagonists delivered intracerebroventricularly (i.c.v.) was undertaken in anesthetized rats. Urethane-anesthetized male rats were implanted into the cerebral ventricle with a cannula for i.c.v. injections, and recording electrodes were placed within the bulbospongiosus (BS) muscle to monitor BS muscle contractions, which were used as a marker for the expulsion phase of ejaculation. Following i.c.v. injection, 7-OH-DPAT induced ejaculation and rhythmic BS muscle contractions. Co-injected i.c.v. with 7-OH-DPAT, the nonselective D(2)/D(3) antagonist (raclopride), and the preferential D(3) antagonist (S(-)-N[n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyanonaphtalene-2-carboxamide; nafadotride) but not the preferential D(2) antagonist ((+/-)-3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole; L 741,626) inhibited the occurrence of ejaculation and BS muscle contractions. These results suggest that i.c.v. delivery of 7-OH-DPAT does represent a pertinent model to investigate the physio-pharmacology of ejaculation. It is inferred that targeting brain D(3) receptors may provide a therapeutic approach for treating ejaculatory disorders in humans.     

Compartmentalization of small ruminant lentivirus between blood and colostrum in infected goats

The compartmentalization of small ruminant lentivirus (SRLV) subtype A (Maedi-Visna virus) and B (caprine arthritis-encephalitis virus) variants was analyzed in colostrum and peripheral blood mononuclear cells of four naturally infected goats. Sequence analysis of DNA and RNA encompassing the V4-V5 env regions showed a differential distribution of SRLV variants between the two compartments. Tissue-specific compartmentalization was demonstrated by phylogenetic analysis in three of the four cases. In these animals colostrum proviral sequences were clustered relative to the blood viral sequences. In one goat, the blood and colostrum-derived provirus sequences were intermingled, suggesting trafficking of virus between the two tissues or mirroring a recent infection. Surprisingly, the pattern of free virus variants in the colostrum of all animals corresponded only partially to that of the proviral form, suggesting that free viruses might not derive from infected colostral cells. The compartmentalization of SRLV between peripheral blood and colostrum indicates that lactogenic transmission may involve specific viruses not present in the proviral populations circulating in the blood.     

Incubation of frozen-thawed llama sperm with seminal plasma

Seminal plasma is intimately connected to sperm physiology and particularly in South American Camelids, has demonstrated to be involved in multiple physiological reproductive events. Different percentages of seminal plasma (0%, 10% and 50%) were added to thawed llama semen samples with the objective of evaluating the interaction with cryopreserved sperm over time (0, 1.5 and 3 hr at 37°C). A total of 20 ejaculates from five adult llama males (n = 5; r = 4) were evaluated. A significant decrease in sperm motility, membrane function and live sperm was observed in all thawed samples (0%, 10% and 50%) at 0 hr when compared to raw semen. Neither morphology nor chromatin condensation was altered in all thawed samples (p > .05), but a significant increase in the percentage of spermatozoa with fragmented DNA was observed after thawing all samples versus raw semen. When evaluating thawed samples over time, a significant decrease of motility and membrane function was observed, while the percentages of total live sperm were preserved over the 3 hr of incubation in all final concentrations evaluated. To conclude, the addition of 10% or 50% of seminal plasma was incapable of preserving motility or membrane function of frozen-thawed llama sperm during 3 hr of incubation.     

Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison

BackgroundManagement of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC.MethodsThis is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups.Results1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14–2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22–2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54–0.69; p<0.001).ConclusionCurative approaches may guarantee long-term survival in case of recurrence.