Cardiac troponin T as a serum biomarker of respiratory impairment in amyotrophic lateral sclerosis.

OBJECTIVE: Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis. METHODS: In this retrospective observation, we analyzed two independent hospital-based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (nd = 298; nv = 49), serum neurofilament light chain (nd = 117; nv = 17), and respiratory tests (nd = 93; nv = 49). RESULTS: Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = -0.45, p = 0.001) and slow vital capacity % (r = -0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62-0.84) and <50% (AUC 0.80, 95% CI 0.68-0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61-0.83) and <50% (AUC 0.79, 95% CI 0.67-0.91). INTERPRETATION: Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function.

Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2ß1 Is Associated with Aggressive Epithelial Ovarian Cancer.

Hepatocyte growth factor receptor (HGFR), also known as c-mesenchymal-epithelial transition factor (c-MET), plays a crucial role in the carcinogenesis of epithelial ovarian cancer (EOC). In contrast, the mechanisms contributing to aberrant expression of HGFR in EOC are not fully understood. In the present study, the expression of HGFR with its prognostic and predictive role was evaluated immunohistochemically in a cohort of 42 primary ovarian cancer patients. Furthermore, we analyzed the dual expression of HGFR and other druggable biomarkers. In the multivariate Cox regression analysis, high HGFR expression was identified as an independent prognostic factor for a shorter progression-free survival (PFS) (hazard ratio (HR) 2.99, 95% confidence interval (CI95%) 1.01-8.91, p = 0.049) and overall survival (OS) (HR 5.77, CI95% 1.56-21.34, p = 0.009). In addition, the combined expression of HGFR, human epidermal growth factor receptor 2 (Her2/neu), epithelial growth factor receptor (EGFR), insulin-like growth factor 1 (IGF1R), Mucin-1 and Integrin α2ß1 further significantly impaired PFS, platinum-free interval (PFI) and OS. Protein co-expression analyses were confirmed by transcriptomic data in a large, independent cohort of patients. In conclusion, new biomarker-directed treatment targets were identified to fight poor prognosis of primary EOC.

Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.

Late Presentation at Primary Diagnosis of Breast Cancer: Patients' Personality Characteristics and Attitudes.

INTRODUCTION: Breast cancer (BC) is the most common cancer in women worldwide. Despite screening and information efforts, about 10% of patients present with tumor size T3 or T4 at primary diagnosis. Late presentation is associated with more advanced tumor stage and consecutively with worse survival rates. OBJECTIVE: This study aimed to evaluate whether patients with a late presentation at primary BC diagnosis differ in their personality from those with early diagnosis. METHODS: In this bicentric, observational study, personality traits, positive and negative affectivity, anxiety, spirituality, illness beliefs, and sociodemographic characteristics were assessed in BC patients who presented with T-stages 3 or 4 (late presenters) and T-stages 1 or 2 (controls) at initial diagnosis. RESULTS: Forty patients (20 controls, 20 late presenters) were interviewed. "Late presenters" perceived their disease as long lasting and had significantly more "positive affectivity" in the current trait. Although no significant associations were found, there was a trend for late presenters to have higher education levels, less spiritual longing, less accurate explanation of their illness, less anxiety in the trait scale, and more conscientiousness than the controls. CONCLUSION: As patients with late presentation for BC differ in specific psychological and sociodemographic characteristics from patients with early BC, the findings of this pilot project warrant additional investigations to identify further specific characteristics and motivations. Identifying patients at risk for late presentation and encouraging them to accept an earlier diagnosis could help to improve their therapy and, finally, their outcome.

Post-Neoadjuvant Gemcitabine and Cisplatin with Regional Hyperthermia for Patients with Triple-Negative Breast Cancer and Non-pCR after Neoadjuvant Chemotherapy: A Single-Institute Experience.

BACKGROUND: Patients with triple-negative primary breast cancer (TNBC) who have residual invasive carcinoma after neoadjuvant chemotherapy have poor prognosis. Proven adjuvant approaches to reduce the risk of recurrence and improve outcome in patients with non-pathological complete response (non-pCR) are limited. METHODS: From our institutional registry, a consecutive case series of patients with operable, unilateral, primary invasive noninflammatory early TNBC of stage I-IIIB and pathologically verified residual cancer cells (no pathological complete response) after neoadjuvant chemotherapy underwent adjuvant treatment with gemcitabine plus cisplatin combined with regional hyperthermia. For quality assurance, we analyzed feasibility, efficacy, and toxicity of all treated patients. Outcome was evaluated for the entire group of patients as well as for the subgroups of patients with or without lymph node involvement at baseline (cN0/ cN+). RESULTS: From August 2012 to January 2019, we offered this treatment to 53 patients at our center as part of routine care. The median follow-up was 38 months. The majority of patients (64.2%) had cT2 tumors at baseline. Twenty-four patients (45%) were clinically node positive as evaluated by sonography. Thirty-nine patients (74%) had grade 3, and 14 patients (26%) had grade 2 tumors. Forty-one patients (76%) showed a regression grade 1 according to Sinn. Patients received a median of six treatment cycles of gemcitabine and cisplatin (range 1-6) combined with 12 applications of regional hyperthermia (median 12, range 2-12). Disease-free survival (DFS) at 3 years was 57.5%. In patients with no lymph node involvement at baseline (cN0), DFS at 3 years was significantly higher than in initially node-positive (cN+) patients (80 vs. 31%; p = 0.001). Overall survival (OS) at 3 years was 81.6%. In patients with no lymph node involvement at baseline (cN0), OS at 3 years was significantly higher than in node-positive (cN+) patients (93 vs. 70.4%; p = 0.02). Overall, grade 3/4 toxicities were leukopenia (38%), thrombocytopenia (4%), and anemia (4%). CONCLUSION: After standard neoadjuvant chemotherapy containing anthracycline plus cyclophosphamide followed by taxanes, addition of adjuvant gemcitabine plus cisplatin in combination with regional hyperthermia was safe and effective in TNBC patients with non-pCR.

Growth restricted placentas show severely reduced volume of villous components with perivascular myofibroblasts.

INTRODUCTION: The restricted placental growth in IUGR is associated with a simultaneous weight and volume restriction for the placental villous tree. It is unknown whether the whole villous tree or only specific parts of it are growth restricted in IUGR. In the case of uniform growth restriction of the villous tree, IUGR placentas could be interpreted as symmetrically smaller versions of normal placentas. Otherwise, IUGR placentas would be morphologically, developmentally and, therefore, functionally different from normal placentas. METHODS: We investigated ten normal and eleven IUGR placentas with quantitative microscopic techniques. Using immunohistochemical detection of placental myofibroblasts (γ-sm-actin) and foetoplacental endothelium (CD34), we distinguished between more centrally located villi showing the presence of myofibroblasts (contractile villi; C-villi) and more peripherally located villi showing the absence of myofibroblasts (noncontractile villi; NC-villi). RESULTS: Compared to normal placentas, IUGR placentas showed significantly reduced mean volume of C-villi, but not of NC-villi. The volume of vessels in both, C-villi and NC-villi, was significantly reduced in IUGR. Additional stereologic estimates confirmed the known alterations in the morphology of NC-villi in IUGR. DISCUSSION: Our results suggest that IUGR placentas are not just smaller but morphologically (and therefore functionally) different from normal placentas. We propose that the reduced volume of C-villi and vessels in C-villi reflects a developmental disturbance in the formation of C-villi, which are mostly composed of stem villi. As such, key pathological villous alterations in IUGR placentas could begin before the formation of intermediate and terminal villi, possibly already in the late first trimester of pregnancy.

Integrin α2ß1 Represents a Prognostic and Predictive Biomarker in Primary Ovarian Cancer.

Currently, the same first-line chemotherapy is administered to almost all patients suffering from primary ovarian cancer. The high recurrence rate emphasizes the need for precise drug treatment in primary ovarian cancer. Being crucial in ovarian cancer progression and chemotherapeutic resistance, integrins became promising therapeutic targets. To evaluate its prognostic and predictive value, in the present study, the expression of integrin α2ß1 was analyzed immunohistochemically and correlated with the survival data and other therapy-relevant biomarkers. The significant correlation of a high α2ß1-expression with the estrogen receptor alpha (ERα; p = 0.035) and epithelial growth factor receptor (EGFR; p = 0.027) was observed. In addition, high α2ß1-expression was significantly associated with a low number of tumor-infiltrating immune cells (CD3 intratumoral, p = 0.017; CD3 stromal, p = 0.035; PD-1 intratumoral, p = 0.002; PD-1 stromal, p = 0.049) and the lack of PD-L1 expression (p = 0.005). In Kaplan-Meier survival analysis, patients with a high expression of integrin α2ß1 revealed a significant shorter progression-free survival (PFS, p = 0.035) and platinum-free interval (PFI, p = 0.034). In the multivariate Cox regression analysis, integrin α2ß1 was confirmed as an independent prognostic factor for both PFS (p = 0.021) and PFI (p = 0.020). Dual expression of integrin α2ß1 and the hepatocyte growth factor receptor (HGFR; PFS/PFI, p = 0.004) and CD44v6 (PFS, p = 0.000; PFI, p = 0.001; overall survival [OS], p = 0.025) impaired survival. Integrin α2ß1 was established as a prognostic and predictive marker in primary ovarian cancer with the potential to stratify patients for chemotherapy and immunotherapy, and to design new targeted treatment strategies.

Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer.

CD3+ and CD8+ lymphocytes are well known prognostic markers in primary ovarian cancer. In contrast, the predictive value of the immune infiltrate concerning treatment response and the involvement of immune heterogeneity between primary and metastatic lesions are poorly understood. In this study, the immune infiltrate of 49 primary tumors and 38 corresponding lesions in the omentum (n = 23) and the peritoneum (n = 15) was immunohistochemically analyzed and correlated with clinicopathological factors and platinum-sensitivity. Immune heterogeneity was observed between paired primary and metastatic lesions for all immune cell phenotypes. The stromal immune infiltrate was higher in the omental lesions than in the primary tumors, which was reflected by CD45 (p=0.007), CD3 (p=0.005), CD8 (p=0.012), and PD-1 (programmed cell-death protein 1) (p=0.013). A higher stromal infiltrate of both CD45+ and CD3+ cells in the omental lesions was associated with the detection of lymph node metastasis (CD45, p=0.018; CD3, p=0.037). Platinum-sensitive ovarian cancers revealed a higher intratumoral CD8+ infiltrate in the peritoneal lesions compared to the primary tumors (p=0.045). In contrast, higher counts of stromal PD-1+ cells in the peritoneal lesions have been associated with reduced platinum-sensitivity (p=0.045). Immune heterogeneity was associated with platinum response and might represent a selection marker for personalized therapy.

The Density of Cell Nuclei at the Materno-Fetal Exchange Barrier is Sexually Dimorphic in Normal Placentas, but not in IUGR.

Placental sexual dimorphism is of special interest in prenatal programming. Various postnatal diseases with gender dependent incidence, especially neuropsychiatric disorders like schizophrenia and autism spectrum disorders, have prenatal risk factors established. However, the functional relevance of placental microarchitecture in prenatal programming is poorly investigated, mainly due to a lack of statistically efficient methods. We hypothesized that the recently established 3D microscopic analysis of villous trees would be able to identify microscopic structural correlates of human placental sexual dimorphism. We analyzed the density of cell nuclei of villous trophoblast, i.e. the materno-fetal exchange barrier, in placentas from term pregnancies. The cell nuclei were grouped into proliferative and non-proliferative nuclei by detection of a proliferation marker (PCNA). Normal female placentas showed a higher density of non-proliferating nuclei (PCNA-negative) in villous trophoblast than normal male placentas. The density of PCNA-negative cell nuclei was higher in placentas of pregnancies with intrauterine growth retardation (IUGR) than in control placentas. The data of the present study shows that the density of non-proliferative cell nuclei in the syncytial layer of villous trophoblast is influenced by fetal sex and by IUGR, while proliferation remains unchanged. A novel concept of post-fusion regulation of syncytial structure and function is proposed.

Current challenges in the diagnosis of zearalenone toxicosis as illustrated by a field case of hyperestrogenism in suckling piglets.

BACKGROUND: The mycotoxin zearalenone (ZEN) causes functional and morphological alterations in reproductive organs of pigs. In the field, diagnosis of ZEN-induced disorders is often challenging, as relevant feed lots are no longer available, or feed analysis results are not conclusive. Here, we report a field case of hyperestrogenism in newborn piglets. Surprisingly, more than 50 fungal metabolites were detected in hay pellets fed to gestating sows, including ZEN and its modified form zearalenone-14-sulfate (ZEN-14-S). Despite the broad contamination range in this unconventional feed component, a definite diagnosis of mycotoxicosis could not be achieved. In this context, current limitations regarding the confirmation of suspected cases of ZEN-induced disorders are discussed, covering both feed analysis and the biomarker approach. CASE PRESENTATION: A piglet producer with 200 sows experienced a sudden increase in suckling piglet losses up to 30% by lower vitality and crushing. Predominant clinical signs were splay legs and signs of hyperestrogenism such as swollen and reddened vulvae in newborn piglets. The first differential diagnosis was ZEN mycotoxicosis although feed batches had not been changed for months with the exception of ground hay pellets, which had been included in the diet five months before. Analysis of hay pellets resulted in a sum value of ZEN and its modified forms of more than 1000 µg/kg, with ZEN-14-S alone accounting for 530 µg/kg. Considering the inclusion rate of 7% in the diet for gestating sows, the severe impact of the additional ZEN load due to the contaminated hay pellets seemed unrealistic but could not be completely excluded either. One month after hay pellets had been removed from the diet no further clinical signs were observed. CONCLUSIONS: Enrichment materials and other fibre sources can contain significant amounts of mycotoxins and should be therefore included in feed analysis. Adequate methods for broad spectrum mycotoxin determination, including modified mycotoxins, are important. As highlighted by this field case, there is a need to establish reliable biomarkers for ZEN exposure in pigs. Currently, available biomarkers do not allow a solid prediction of the ZEN intake of pigs under field conditions, which limits their application to experimental studies.

Weekly High-dose 5-Fluorouracil as 24-hour Infusion Combined with Sodium Folinic Acid (AIO regimen) Plus Irinotecan in Second-line and Sequential Therapy of Metastatic Colorectal Cancer (CRC).

BACKGROUND/AIM: The aim of this work was to evaluate the efficacy and safety of second-line treatment with weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) combined with sodium folinic acid (FA) (AIO-regimen) plus irinotecan (Iri.) after pretreatment with AIO-regimen plus oxaliplatin (L-OHP). PATIENTS AND METHODS: Patients with non-resectable distant CRC metastases were enrolled in a prospective phase II study for palliative second-line treatment after previous progression of first-line treatment in accordance with the AIO-regimen plus oxaliplatin. On an outpatient basis, the patients received a treatment regimen comprising of weekly 80 mg/m2 irinotecan in the form of a 1-hour i.v. infusion and 2,000 mg/m2 5-FU combined with 500 mg/m2 sodium folinic acid administered as a 24-h infusion i.v. once weekly. RESULTS: During second-line treatment, a total of 59 patients received 520 chemotherapy applications. As the main higher-grade symptom of toxicity, diarrhea (NCI-CTC-toxicity grade 3) presented in 8 patients (13.6%, 95%CI=5.1-23.7), followed by leukocytopenia (CTC grade 3) in 3 patients (5.1%, 95%CI=0-11.9), followed by thrombocytopenia (CTC grade 3) in 1 patient (1.7%, 95%CI=0-5.1). Fifty-nine patients were evaluable for treatment response. The remission data can be summarized as follows: complete remission (CR); n=0; partial remission (PR); n=6 (10%; 95%CI=3.4-18.6); stable disease (SD); n=31 (53%; 95%CI=39.0-64.4); progressive disease (PD); n=19 (33%; 95%CI=20.3-44.1). The median progression-free survival (PFS) rate (n=59) was 4.2 months (range=3.8-5.8 months). The median survival time counted from the start of second-line treatment (n=59) 14.2 months (range 8.2-17.3 months) and the median survival time counted from the start of first-line therapy (n=59) 25 months (range 19-27 months). CONCLUSION: Palliative second-line treatment according to the AIO regimen plus irinotecan offers both a favourable toxicity profile and promising efficacy in second-line and palliative sequential therapy.

Chemotherapy and Post-traumatic Stress in the Causation of Cognitive Dysfunction in Breast Cancer Patients.

Background: Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy; this explanation, however, fails to account for cognitive dysfunction observed in chemotherapy-naïve patients. In a controlled, longitudinal, multisite study, we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress. Methods: Newly diagnosed breast cancer patients and healthy control subjects, age 65 or younger, underwent three assessments within one year, including paper-and-pencil and computerized neuropsychological tests, clinical diagnostics of post-traumatic stress disorder (PTSD), and self-reported cognitive function. Analysis of variance was used to compare three groups of participants-patients who did or did not receive chemotherapy and healthy control subjects-on age- and education-corrected cognitive performance and cognitive change. Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models. All statistical tests were two-sided. Results: Of 226 participants (166 patients and 60 control subjects), 206 completed all assessment sessions (attrition: 8.8%). Patients demonstrated overall cognitive decline (group*time effect on composite z -score: -0.13, P = .04) and scored consistently worse on Go/Nogo errors. The latter effect was mediated by PTSD symptoms (mediation effect: B = 0.15, 95% confidence interval = 0.02 to 0.38). Only chemotherapy patients showed declined reaction time on a computerized alertness test. Overall cognitive performance correlated with self-reported cognitive problems at one year ( T = -0.11, P = .02). Conclusions: Largely irrespective of chemotherapy, breast cancer patients may encounter very subtle cognitive dysfunction, part of which is mediated by cancer-related post-traumatic stress. Further factors other than treatment side effects remain to be investigated.

Increased trace amine-associated receptor 1 (TAAR1) expression is associated with a positive survival rate in patients with breast cancer.

PURPOSE: A correlation between breast cancer and thyroid disorders has been described in previous studies. Degraded thyroid hormones are referred to as trace amines. These endogenous amines have the ability to bind to the G-protein-coupled receptor TAAR1 (trace amine-associated receptor) and thereby activate it. TAAR1 is able to modulate the serotonergic and dopaminergic system in the brain and has so far been studied in the neurological field. The following study represents the first investigation of the regulation of TAAR1 in primary breast cancer (no metastases, M0). METHODS: Immunohistochemical analyses were carried out to detect TAAR1 expression in formalin fixed paraffin embedded breast cancer samples. Survival times of primary breast cancer patients (M0) with and without TAAR1 expression in their tumours were compared by Kaplan-Meier curves, and correlations between ordinal variables were determined with Spearman's rank correlation coefficient. RESULTS: The investigation showed a correlation between TAAR1 expression and tumour differentiation grade. A well differentiated tumour grade (G1) was associated with higher TAAR1 expression and HER2 and HER4 positivity predicted higher TAAR1 expression. A TAAR1 overexpression (IRS ≥ 6) was associated with significantly longer overall survival (OS) (p = 0.02) than that of reduced TAAR1 expression (IRS < 6) during a maximum follow-up of 14 years, demonstrating that TAAR1 has a favourable effect on OS of early breast cancer patients. CONCLUSIONS: We conclude that TAAR1 seems to be an independent predictor for breast cancer survival. Modulation of TAAR1 may represent a novel targeting strategy for breast cancer prevention and therapy.

Dynamic modeling of uteroplacental blood flow in IUGR indicates vortices and elevated pressure in the intervillous space - a pilot study.

Ischemic placental disease is a concept that links intrauterine growth retardation (IUGR) and preeclampsia (PE) back to insufficient remodeling of uterine spiral arteries. The rheological consequences of insufficient remodeling of uterine spiral arteries were hypothesized to mediate the considerably later manifestation of obstetric disease. However, the micro-rheology in the intervillous space (IVS) cannot be examined clinically and rheological animal models of the human IVS do not exist. Thus, an in silico approach was implemented to provide in vivo inaccessible data. The morphology of a spiral artery and the inflow region of the IVS were three-dimensionally reconstructed to provide a morphological stage for the simulations. Advanced high-end supercomputing resources were used to provide blood flow simulations at high spatial resolution. Our simulations revealed turbulent blood flow (high-velocity jets and vortices) combined with elevated blood pressure in the IVS and increased wall shear stress at the villous surface in conjunction with insufficient spiral artery remodeling only. Post-hoc histological analysis of uterine veins showed evidence of increased trophoblast shedding in an IUGR placenta. Our data support that rheological alteration in the IVS is a relevant mechanism linking ischemic placental disease to altered structural integrity and function of the placenta.

Clinically assessed posttraumatic stress in patients with breast cancer during the first year after diagnosis in the prospective, longitudinal, controlled COGNICARES study.

OBJECTIVE: There is ongoing debate whether cancer qualifies as traumatic stressor. We investigated prevalence and course of posttraumatic stress in patients with early breast cancer (BC) during their first year after diagnosis and determined effects of mastectomy and chemotherapy. METHODS: Patients with stage 0-III BC aged ≤65 years were evaluated with the Structured Clinical Interview for DSM-IV modules for acute and posttraumatic stress disorder (ASD and PTSD, respectively) before treatment, after chemotherapy, and 1 year after diagnosis. Matched controls were assessed at matched intervals. Effects of time, mastectomy, and chemotherapy on BC-related PTSD symptom severity were tested with linear mixed model analysis. RESULTS: Stress disorder (ASD or PTSD) related to BC was diagnosed in 6 (3.6%) of 166 patients before treatment and in 3 patients (2.0%) 1 year later. The rate of patients who experienced PTSD symptoms related to BC decreased from 82.5 to 57.3% (p < 0.001), and the mean of BC-related PTSD symptoms diminished from 3.1 to 1.7 (p < 0.001). Only university education significantly predicted the course of BC-related PTSD symptom severity (p = 0.009). In 60 controls, no diagnosis of stress disorder, a rate of 18% women experiencing PTSD symptoms, and a mean of 0.4 PTSD symptoms (p vs. patients <0.001) were found. CONCLUSIONS: Most newly diagnosed patients with BC experience PTSD symptoms, whereas full diagnoses of DSM-IV stress disorder are rare. Symptoms diminish somewhat within 1 year furthered by university education but independently from mastectomy and chemotherapy. Throughout the year after diagnosis, having BC entails markedly increased PTSD symptom burden. Copyright © 2016 John Wiley & Sons, Ltd.

Successful Multidisciplinary Treatment with Secondary Metastatic Liver Resection after Downsizing by Palliative Second-Line Treatment of Colorectal Cancer: A Curative Option.

INTRODUCTION: The prognostic outcome following progression after palliative first-line treatment for patients suffering from metastatic colorectal adenocarcinoma is generally poor. Long-term relapse-free survival with palliative second-line treatment may be achieved in only a limited number of individual cases. CASE REPORT: A 37-year-old patient presented with bilobar liver metastases of colon cancer confirmed by histology with wild-type K-RAS (exon 2). Due to progressive disease after eight cycles of first-line therapy with FOLFIRI plus cetuximab, second-line chemotherapy with modified FOLFOX4 (mFOLFOX4) plus bevacizumab was initiated. During four cycles of mFOLFOX4 plus bevacizumab (2 months), no higher-grade toxicity occurred. Liver MRI with contrast medium revealed downsizing of the segment II/III metastases, as well as regressive, small, faint, hardly definable lesions in segments VI and IVb. The interdisciplinary tumor board of the University of Erlangen thus decided to perform resection of the liver metastases. Segments II and III were resected, and the liver metastases in segments IVa and VI were excised (R0). Histopathology confirmed three of the R0-resected metastases to be completely necrotic, with residual scarring. As perioperative therapy, four additional cycles of mFOLFOX4 plus bevacizumab were administered postoperatively. No higher-grade toxicity was observed. Three years after the initial diagnosis, the patient is relapse free, professionally fully reintegrated, and has an excellent performance status. CONCLUSION: Patients suffering from metastatic colorectal cancer may benefit from multidisciplinary treatment with secondary metastatic liver resection after downsizing by palliative second-line treatment. In individual cases, patients may even have a curative treatment option, provided that close interdisciplinary collaboration exists.

Novel 3D light microscopic analysis of IUGR placentas points to a morphological correlate of compensated ischemic placental disease in humans.

The villous tree of the human placenta is a complex three-dimensional (3D) structure with branches and nodes at the feto-maternal border in the key area of gas and nutrient exchange. Recently we introduced a novel, computer-assisted 3D light microscopic method that enables 3D topological analysis of branching patterns of the human placental villous tree. In the present study we applied this novel method to the 3D architecture of peripheral villous trees of placentas from patients with intrauterine growth retardation (IUGR placentas), a severe obstetric syndrome. We found that the mean branching angle of branches in terminal positions of the villous trees was significantly different statistically between IUGR placentas and clinically normal placentas. Furthermore, the mean tortuosity of branches of villous trees in directly preterminal positions was significantly different statistically between IUGR placentas and clinically normal placentas. We show that these differences can be interpreted as consequences of morphological adaptation of villous trees between IUGR placentas and clinically normal placentas, and may have important consequences for the understanding of the morphological correlates of the efficiency of the placental villous tree and their influence on fetal development.