Risk of residual breast tissue after skin-sparing mastectomy

Abstract: Skin‐sparing mastectomy (SSM) is an accepted surgical option for breast cancer treatment. SSM allows for preservation of the skin envelope and improved cosmesis. Despite initial concerns, large series have not revealed higher recurrence rates. There is, however, a paucity of data regarding the rates of residual breast tissue (RBT) left behind after SSM, what factors influence this, and the oncologic implications of RBT. Retrospective review identified 288 total mastectomies. Patients who had undergone SSM with excision of additional skin for reconstructive purposes, either at the initial oncologic surgery or at subsequent revision, were included in the final study group. Pathologic analysis was performed to evaluate excised skin. Data regarding demographics, tumor type, and treatment were collected. Comparison between patients who had pathologically confirmed RBT in the excised skin and those who did not was performed. Of 288 total mastectomies, 92 were SSM’s, and 66 had skin specimens removed for nononcologic reasons, of these, 4 (6%) had RBT. Age at diagnosis (p = 0.806), BMI (p = 0.531), tumor size (p = 0.922), and estrogen receptor status (p > 0.999) did not contribute to increased RBT risk. At median follow‐up of 33.5 months, there have been no recurrences. In addition, cost analysis reveals it is likely not cost‐effective to perform pathologic evaluation of these specimens. SSM, performed at an academic medical center by fellowship‐trained surgeons, has a very low rate of RBT, and does not compromise oncologic outcomes. Routine pathologic assessment of these skin specimens, removed for nononcologic reasons, may not be required.     

The role of the kidney in blood volume regulation: the kidney as a regulator of the hematocrit

The kidney plays a pivotal role in the regulation of blood volume by controlling the plasma volume and red blood cell (RBC) mass. Further, it is proposed that the kidney coordinates the relative volumes of these 2 blood components and in so doing regulates the hematocrit. This novel function as proposed is a functional concept whereby the kidney does not simply produce erythropoietin, but that the kidney regulates the hematocrit is termed the critmeter function. The kidney is unique in that it can indirectly report on blood volume as a tissue oxygen signal. It is proposed that the kidneys detect small changes in tissue oxygen tension for erythropoietin production at the critmeter, a functional unit of marginal oxygen tension within the kidneys. As the production of erythropoietin is modulated by angiotensin II, the renin-angiotensin system entrains the production of erythropoietin as part of the effector signals of the feedback loop of blood volume regulation. Collectively, the consideration of these points generates a paradigm shift in our understanding of blood volume regulation in that the role of the kidney may be expanded from simply "producing" erythropoietin to regulating the hematocrit. Further, this concept broadens the scope of the traditionally identified effector mechanisms of plasma volume regulation to include the modulation of erythropoietin production and hence RBC mass. The inclusion of both plasma volume and RBC mass as factors targeted by the effector signals recapitulates that whole blood volume is sensed and reported in the afferent signals. In summary, distinct sensing and effector mechanisms for regulating the volume of the two components of whole blood (plasma and red cell mass) are recognized. The coupling of the regulation of these 2 components of blood volume is highlighted.     

Intratumoral expression level of epidermal growth factor receptor and cytokeratin 5/6 is significantly associated with nodal and distant metastases in patients with basal-like triple-negative breast carcinoma

Triple-negative (TN) breast carcinoma, characterized by estrogen receptor, progesterone receptor, and HER2 negativity, is a group of aggressive tumors that can be further classified into 2 subtypes: basal-like, defined as CK5/6 and/or epidermal growth factor receptor (EGFR) positive by immunohistochemistry; and non-basal-like. Clinical characteristics and tumor profiles were analyzed in 105 cases of TN tumors. Among these cases, 35 had distant metastasis, 34 had axillary nodal metastasis only, and 36 were nodal negative. Our results indicate basal-like TN breast tumors with nodal and distant metastases are significantly associated with a higher intratumoral expression of EGFR and CK5/6 compared to those in the nodal negative group. High level of intratumoral EGFR and CK5/6 expression may play a role in development of nodal or distant metastases in patients with basal-like TN tumors and may be predictive of metastatic disease. Furthermore, EGFR targeted therapy may be potentially useful in the treatment of basal-like TN breast cancer.     

Disease burden of human papillomavirus infection in the Netherlands, 1989–2014: the gap between females and males is diminishing

Purpose

Besides cervical cancer, HPV infection is linked to a multitude of diseases in both males and females, suggesting that vaccination programmes should be re-evaluated, with a judicious assessment made of the disease burden stratified by sex, age, and genotype. Projections of burden into the near future are also needed to provide a benchmark for evaluating the impact of vaccination programmes, and to assess the need for scaling-up preventive measures.

Methods

Using the disability-adjusted life-years (DALY) measure, we estimated the total HPV-associated disease burden in the Netherlands. Annual cancer registrations over the period 1989–2014 for all cancers with an aetiological link to HPV infection were retrieved, supplemented by incidence data on high-grade cervical intraepithelial neoplasia (CIN) and anogenital warts.

Results

Over the recent period 2011–2014, the average annual HPV disease burden was 10,600 DALYs (95% credible interval (CrI):10,260–10,960) in females and 3,346 DALYs (95% CrI: 2,973–3,762) in males. Burden was dominated by cervical cancer, but its share amongst women decreased from 89% in 1989 to 77% in 2014. The male share of the total disease burden increased from 9.8% in 1989 to 26% in 2014. In 2023 (before the expected clinical impact from vaccinating girls), total burden is forecasted at 1.3-fold larger than in 2014.

Conclusions

The HPV-associated disease burden is higher than that reported for any other infectious disease in the Netherlands, with a larger burden observed in women than in men. The rapidly rising male share of the total burden underlines the prioritization of male HPV-related disease in prevention programmes.