Intra-mammary tumor location does not influence prognosis but influences the prevalence of axillary lymph-node metastases

Background The number of axillary lymph-node metastases is not only a function of disease progression in primary breast cancer, but is also influenced by the intra-mammary location of the tumor. Nevertheless, the prognostic role of the tumor site is discussed controversially. The objective of this study was to analyze the impact of primary-tumor location on axillary lymph-node involvement, relapse, and mortality risk by univariate and multivariate analysis, in patients both with and without systemic and loco-regional treatment.Method Retrospective analysis was conducted on 2,414 patients at the I. Frauenklinik, Ludwig-Maximilians University, Munich and Berlin-Charlottenburg, who underwent R₀ resection of the primary tumor and systematic axillary lymph-node dissection (at least five lymph nodes resected) for UICC I-III-stage breast cancer. Patients with unknown tumor site, multifocal tumor spread, central tumor location, or tumor location within 15° of the border between outer and inner quadrants were excluded from the study. Median observation time was 6.7 years.Results The primary tumor site was within or between the medial quadrants of the breast in 33.6% of the patients (n=810) and in the lateral hemisphere of the breast in 66.4% (n=1,604). Tumor size, histopathological grading, and estrogen receptor status were balanced between patients with lateral and medial tumor location. Metastatic axillary lymph-node involvement was significantly associated with a lateral tumor location (P<0.0001). The mean number of axillary lymph-node metastases was increased by 29% in cases with lateral tumor location (2.2 vs 1.7, P=0.003). In a multivariate logistic regression analysis allowing for tumor location, estrogen receptor status, grading and tumor size, tumor location was confirmed as a significant risk factor (P=0.02) for axillary lymph-node involvement. Tumor location, however, did not correlate with either disease-free survival (DFS) or overall survival (OS), by univariate (DFS: P=0.41; OS: P=0.57) or by multivariate analysis (DFS: P=0.16; OS: P=0.98).Conclusion We conclude that there is no sufficient evidence to support any independent prognostic significance of intra-mammary tumor location in early breast cancer. However, medial tumor location may lead to the underestimation of axillary lymph-node involvement.     

Management of skin-sparing mastectomy: results of a survey of German hospitals

BACKGROUND: The aim of this study was to evaluate the current management of skin-sparing mastectomy in German hospitals and to determine its oncologic safety. For this purpose, 100 surgeons were surveyed regarding their use of skin-sparing mastectomy. RESULTS: Almost all surveyed hospitals performed skin-sparing mastectomy. Most of them believe that the recurrence rate is equal to that of conventional mastectomy. 95% regard inflammatory cancer as a contraindication to skin-sparing surgery. Most of the hospitals thin out the skin without leaving any macroscopic glandular tissue behind, and 73% leave the nipple-areola complex (NAC) on the basis of frozen sections. Volume replacement is most commonly done with latissimus dorsi muscle flaps and pedicled TRAM flaps. In 76% of the surveyed hospitals, reconstruction after mastectomy is performed by the gynecological department. CONCLUSION: Skin-sparing mastectomy is considered to be the best cosmetic option for breast reconstruction in selected breast cancer patients. At present, statistical proof of its oncologic safety is lacking. The surgical techniques used for skin-sparing mastectomy have not yet been standardized. In order to achieve standardization, careful discussion-making and evaluation remain important.     

Pregnancy-associated breast cancer -- special features in diagnosis and treatment

For obvious psychological reasons it is difficult to associate pregnancy -- a life-giving period of our existence -- with life-threatening malignancies. Symptoms pointing to malignancy are often ignored by both patients and physicians, and this, together with the greater difficulty of diagnostic imaging, probably results in the proven delay in the detection of breast cancers during pregnancy. The diagnosis and treatment of breast cancer are becoming more and more important, as the fulfillment of the desire to have children is increasingly postponed until a later age associated with a higher risk of carcinoma, and improved cure rates of solid tumors no longer exclude subsequent pregnancies. The following article summarizes the special features of the diagnosis and primary therapy of pregnancy-associated breast cancer with particular consideration of cytostatic therapy.     

Cigarette smoke inhibits cytosolic but not microsomal epoxide hydrolase of human lung.

The effect of cigarette smoke exposure on the activity of cytosolic and microsomal epoxide hydrolase (EH) has been investigated in human lung. Patients were classified as 'recent smokers' (n = 9) or 'non-recent smokers' (n = 10) according to whether they were or were not still smoking 1 month before surgery. Cytosolic EH was measured with [3H]trans-stilbene oxide as a substrate, whereas microsomal EH was measured with [7-3H]styrene oxide as a substrate. Microsomal EH activity did not differ between recent smokers (2.51 +/- 0.93 nmol min-1 mg-1) and non-recent smokers (2.74 +/- 1.10 nmol min-1 mg-1), whereas cytosolic EH activity was significantly lower in recent smokers (6.46 +/- 1.79 pmol min-1 mg-1) than in non-recent smokers (8.41 +/- 2.09 pmol min-1 mg-1, P less than 0.05). Cytosolic EH activity was correlated with the number of days that had passed since the cessation of smoking (r = 0.58, P less than 0.05) and the effect was dose-dependent, since the enzyme activity was inversely correlated with the number of cigarettes smoked per day (r = 0.85, P less than 0.01). This suggests that recent smoking exposure inhibits the activity of cytosolic EH but not microsomal EH, and that the inhibition increases with the number of cigarettes smoked per day. The contribution of cytosolic enzymes to xenobiotic metabolism may be remarkable in extrahepatic tissues. The inhibition of cytosolic EH by tobacco smoke may reduce the inactivation of carcinogenic epoxides in human lung tissues and so may increase a person's susceptibility to lung cancer.     

Modelling the potential prevention benefits of a treat‐all hepatitis C treatment strategy at global,regional and country levels: A modelling study

The World Health Organization (WHO) recently produced guidelines advising a treat‐all policy for HCV to encourage widespread treatment scale‐up for achieving HCV elimination. We modelled the prevention impact achieved (HCV infections averted [IA]) from initiating this policy compared with treating different subgroups at country, regional and global levels. We assessed what country‐level factors affect impact. A dynamic, deterministic HCV transmission model was calibrated to data from global systematic reviews and UN data sets to simulate country‐level HCV epidemics with ongoing levels of treatment. For each country, the model projected the prevention impact (in HCV IA per treatment undertaken) of initiating four treatment strategies; either selected randomly (treat‐all) or targeted among people who inject drugs (PWID), people aged ≥35, or those with cirrhosis. The IA was assessed over 20 years. Linear regression was used to identify associations between IA per treatment and demographic factors. Eighty‐eight countries (85% of the global population) were modelled. Globally, the model estimated 0.35 (95% credibility interval [95%CrI]: 0.16‐0.61) IA over 20 years for every randomly allocated treatment, 0.30 (95%CrI: 0.12‐0.53) from treating those aged ≥35 and 0.28 (95%CrI: 0.12‐0.49) for those with cirrhosis. Globally, treating PWID achieved 1.27 (95%CrI: 0.68‐2.04) IA per treatment. The IA per randomly allocated treatment was positively associated with a country's population growth rate and negatively associated with higher HCV prevalence among PWID. In conclusion, appreciable prevention benefits could be achieved from WHO’s treat‐all strategy, although greater benefits per treatment can be achieved through targeting PWID. Higher impact will be achieved in countries with high population growth.     

The Association of Stigma with Self-Reported Access to Medical Care and Antiretroviral Therapy Adherence in Persons Living with HIV/AIDS

Background  

The stigma of HIV-infection may profoundly affect the lives of persons living with HIV/AIDS (PLHA). However few studies have examined the association of HIV stigma with multiple components of HIV treatment and care.     

Expression and function of pvcrt-o, a Plasmodium vivax ortholog of pfcrt, in Plasmodium falciparum and Dictyostelium discoideum

Chloroquine resistance in Plasmodium vivax threatens the use of this drug as first-line treatment for millions of people infected each year worldwide. Unlike Plasmodium falciparum, in which chloroquine resistance is associated with mutations in the pfcrt gene encoding a digestive vacuole transmembrane protein, no point mutations have been associated with chloroquine resistance in the P. vivax ortholog gene, pvcrt-o (also called pvcg10). However, the question remains whether pvcrt-o can affect chloroquine response independent of mutations. Since P. vivax cannot be cultured in vitro, we used two heterologous expression systems to address this question. Results from the first system, in which chloroquine sensitive P. falciparum parasites were transformed with pvcrt-o, showed a 2.2-fold increase in chloroquine tolerance with pvcrt-o expression under a strong promoter; this effect was reversed by verapamil. In the second system, wild type pvcrt-o or a mutated form of the gene was expressed in Dictyostelium discoideum. Forms of PvCRT-o engineered to express either lysine or threonine at position 76 produced a verapamil-reversible reduction of chloroquine accumulation in this system to 60% of that in control cells. Our data support an effect of PvCRT-o on chloroquine transport and/or accumulation by P. vivax, independent of the K76T amino acid substitution.