Perioperative management of rare coagulation factor deficiency states in cardiac surgery

Abstract

Rare bleeding disorders (RBDs) include the hereditary deficiency of fibrinogen, factor (F)II, FV, FV + FVIII, FVII, FX, FXI or FXIII. RBDs do not confer a protective effect against atheromatous plaque formation, and thus the need for cardiovascular (CV) surgery in RBD patients is expected to increase with improved healthcare access (diagnosis and management) and longevity of the population. Clinical data regarding the management of RBDs in this setting are sparse, but the perioperative care team is obliged to gain a better understanding on available biological and pharmacological hemostatic agents. Perioperative management of RBDs in CV surgery is further complicated by heparin anticoagulation, haemodilution, and consumption of procoagulant and anticoagulant proteins associated with cardiopulmonary bypass (CPB). The aims of this review are to summarize pathophysiology of RBDs and laboratory monitoring pertinent to CV surgery, available factor replacement agents, and to provide the framework for perioperative coagulation management of RBD patients.

http://ift.tt/2wAxtK5

High quality of evidence is uncommon in Cochrane systematic reviews in Anaesthesia, Critical Care and Emergency Medicine.

BACKGROUND: The association between the quality of evidence in systematic reviews and authors' conclusions regarding the effectiveness of interventions relevant to anaesthesia has not been examined. OBJECTIVE: The objectives of this study were: to determine the proportion of systematic reviews in which the authors made a conclusive statement about the effect of an intervention; to describe the quality of evidence derived from outcomes in reviews that used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) working group system for grading the quality of evidence; and to identify review characteristics associated with conclusiveness. DESIGN: Cross-sectional analysis of Cochrane systematic reviews from the Anaesthesia, Critical Care and Emergency Review Group was undertaken. DATA SOURCES: The Cochrane webpage was used to identify reviews for inclusion ( http://.ace.cochrane.org/). ELIGIBILITY CRITERIA: New and updated versions of systematic reviews published up to 17 September 2015 were eligible. Protocols for systematic reviews were excluded. RESULTS: A total of 159 reviews were included. GRADE was used in 103 reviews (65%). Of these, high-level evidence for the primary outcome was identified in 11 reviews (10%). The main reasons that quality of evidence for the primary outcome was downgraded were risk of bias (n = 44; 43%) and imprecision (n = 36; 35%). Authors of 47% (n = 75) of the total number of reviews made conclusive statements about the effects of interventions. Independent predictors of conclusiveness in the subgroup of reviews with GRADE assessments were quality of evidence for the primary outcome (odds ratio 2.03; 95% confidence interval: [1.18 to 3.52] and an increasing number of studies included in reviews (OR 1.05; 95% CI: [1.01 to 1.09]). CONCLUSION: It was common for conclusive statements to be made about the effects of interventions despite evidence for the primary outcome being rated less than high quality. Improving methodological quality of trials would have the greatest impact on improving the quality of evidence. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/OBJ4xP (C) 2017 European Society of Anaesthesiology

http://ift.tt/2w6n0TO

Enlighting the Shadow for Advanced Hepatocellular Carcinoma: Immunotherapy with Immune Checkpoint Inhibitors

Abstract

Hepatocellular carcinoma has still been one of the cancer with increasing incidence and highest mortality rate in the world. Although many new promising developments have been defined in hepatocarcinogenesis, with a short survival the treatment of patients with advanced hepatocellular carcinoma is an emerging issue. On the recent decade, only one anti-angiogenic agent sorafenib improved overall survival with costing a hardly manageable toxicity. Novel immunotherapeutic agents, especially immune checkpoint inhibitors are on the edge of more effective but less toxic treatments for these patients. In this article the activity of immune checkpoint inhibitors, anti-CTLA-4 and anti-PD1 antibodies for the treatment of patients with advanced hepatocellular cancer will be reviewed.

http://ift.tt/2vhKN1K

The impact of adjuvant therapy for patients with high-risk diffuse WHO grade II glioma

Abstract

Despite recent randomized, prospective evidence supporting use of RT and chemotherapy (CRT) for high-risk low-grade gliomas (LGG), many patients have historically received RT alone, chemotherapy alone or observation postoperatively. The purpose of this study is to evaluate outcomes for historical treatments in comparison to CRT for high-risk diffuse WHO grade II glioma patients. Records from 309 adults with WHO grade II glioma (1997–2008) eligible for RTOG 9802 (incomplete resection/biopsy or age ≥40 years) were retrospectively reviewed. Kaplan–Meier estimates were used for progression-free survival (PFS) and overall survival (OS). The Cox proportional hazards model was used for estimates of risk ratios for univariate and multivariate analyses. Median follow-up was 10.6 years. Adjuvant treatments included radiotherapy (RT) alone (45%), observation (31%), CRT (21%) and chemotherapy alone (3%). Non-astrocytic histology, TERT promoter mutation, 1p/19q codeletion and extensive resections were associated with improved PFS and OS on univariate analysis (all p < 0.05). IDH mutations and adjuvant CRT was associated with improved PFS (all p < 0.05). On multivariate analysis, histology, molecular grouping and extent of resection were significantly associated with PFS and OS. In addition, multivariate analysis revealed that CRT was associated with improved PFS and OS compared with RT alone, and improved PFS compared with observation. This study confirms the benefit of adding chemotherapy to RT compared with RT alone or observation. These findings emphasize the need for aggressive treatment in patients with high-risk LGG.

http://ift.tt/2vZTfW9

Biomarkers, imaging and multifocality in intraductal papillary mucinous neoplasms: relevant for decision making?

Future Oncology, Ahead of Print.


http://ift.tt/2vqEBnp

PDL-1/PD1 inhibitors: antibody or antinobody?

Future Oncology, Ahead of Print.


http://ift.tt/2v7EDp5

Do all aromatase inhibitors have similar efficacy and safety?

Future Oncology, Ahead of Print.


http://ift.tt/2vqtQBA

Single Dose of the CXCR4 Antagonist BL-8040 Induces Rapid Mobilization for the Collection of Human CD34+ Cells in Healthy Volunteers

Purpose: The potential of the high affinity CXCR4 antagonist BL-8040 as a monotherapy mobilizing agent and its derived graft composition and quality were evaluated in a phase I clinical study in healthy volunteers (NCT02073019). <p>Experimental Design: The first part of the study was a randomized, double-blind, placebo-controlled dose escalation phase. The second part of the study was an open label phase, in which 8 subjects received a single injection of BL-8040 (1mg/kg) and approximately 4hrs later underwent a standard leukapheresis procedure. The engraftment potential of the purified mobilized CD34+ cells was further evaluated by transplanting the cells into NSG immune deficient mice.</p> <p>Results: BL-8040 was found safe and well tolerated at all doses tested (0.5-1 mg/kg). The main treatment related AEs were mild to moderate. Transient injection site and systemic reactions were mitigated by methylprednisolone, paracetamol and promethazine pre-treatment. In the first part of the study BL-8040 triggered rapid and substantial mobilization of WBCs and CD34+ cells in all tested doses. 4hrs post dose, the count rose to a mean of 8, 37, 31 and 35cells/µL (placebo, 0.5, 0.75 and 1mg/kg, respectively). FACS analysis revealed substantial mobilization of immature dendritic, T, B and NK cells. In the second part the mean CD34+/kg collected were 11.6 x10⁶ cells/kg. The graft composition was rich in immune cells.</p> <p>Conclusion: The current data demonstrate that BL-8040 is a safe and effective monotherapy strategy for the collection of large amounts of CD34+ cells and immune cells in a one-day procedure for allogeneic HSPC transplantation.<br />

http://ift.tt/2xewR9Z

Sequential, Multiple Assignment, Randomized Trial Designs in Immuno-Oncology Research

Clinical trials investigating immune checkpoint inhibitors have led to the approval of anti-CTLA-4 (cytotoxic T-lymphocyte antigen-4), anti-PD-1 (programmed death-1) and anti-PD-L1 (PD-ligand 1) drugs by the United States Food & Drug Administration (FDA) for numerous tumor types. In the treatment of metastatic melanoma, combinations of checkpoint inhibitors are more effective than single agent inhibitors, but combination immunotherapy is associated with increased frequency and severity of toxicity. There are questions about the use of combination immunotherapy or single agent anti-PD-1 as initial therapy and the number of doses of either approach required to sustain a response. In this paper, we describe a novel use of sequential multiple assignment randomized trial (SMART) design to evaluate immune checkpoint inhibitors to find treatment regimens that adapt within individual based on intermediate response and lead to the longest overall survival. We provide a hypothetical example SMART design for BRAF wild-type metastatic melanoma as a framework for investigating immunotherapy treatment regimens. We compare implementing a SMART design to implementing multiple traditional randomized clinical trials. We illustrate the benefits of a SMART over traditional trial designs and acknowledge the complexity of a SMART.  SMART designs may be an optimal way to find treatment strategies that yield durable response, longer survival, and lower toxicity.

http://ift.tt/2vZOYSt

Targeting phosphatidylinositol 3-kinase signaling pathway for therapeutic enhancement of vascular-targeted photodynamic therapy

Vascular-targeted photodynamic therapy (PDT) selectively disrupts vascular function by inducing oxidative damages to the vasculature, particularly endothelial cells. Although effective tumor eradication and excellent safety profile are well demonstrated in both preclinical and clinical studies, incomplete vascular shutdown and angiogenesis are known to cause tumor recurrence after vascular-targeted PDT. We have explored therapeutic enhancement of vascular-targeted PDT with phosphatidylinositol 3-kinase (PI3K) signaling pathway inhibitors because the activation of PI3K pathway was involved in promoting endothelial cell survival and proliferation after PDT. Here three clinically relevant small molecule inhibitors (BYL719, BKM120 and BEZ235) of the PI3K pathway were evaluated in combination with verteporfin-PDT. Although all three inhibitors were able to synergistically enhance PDT response in endothelial cells, PDT combined with dual PI3K/mTOR inhibitor BEZ235 exhibited the strongest synergism, followed in order by combinations with pan-PI3K inhibitor BKM120 and p110α isoform-selective inhibitor BYL719. Combination treatments of PDT and BEZ235 exhibited a cooperative inhibition of anti-apoptotic Bcl-2 family protein Mcl-1 and induced more cell apoptosis than each treatment alone. In addition to increasing treatment lethality, BEZ235 combined with PDT effectively inhibited PI3K pathway activation and consequent endothelial cell proliferation after PDT alone, leading to a sustained growth inhibition. In the PC-3 prostate tumor model, combination treatments improved treatment outcomes by turning a temporary tumor regrowth delay induced by PDT alone to a more long-lasting treatment response. Our study strongly supports the combination of vascular-targeted PDT and PI3K pathway inhibitors, particularly mTOR inhibitors, for therapeutic enhancement.

http://ift.tt/2isFTNn

Estrogen receptor {beta} is a novel target in acute myeloid leukemia

Acute myeloid leukemia (AML) is a devastating disease characterized by poor patient outcome and suboptimal chemotherapeutics. Here, a high throughput screen identified diosmetin, a citrus flavonoid, with anti-AML activity. Diosmetin imparted selective toxicity against leukemia and leukemia stem cells in vitro and in vivo with no effect on normal hematopoietic stem cells. Mechanistically, we demonstrated that diosmetin targets estrogen receptor (ER) β. ERβ expression conferred cell sensitivity, as patient-derived AML cells with high levels of ERβ were sensitive whereas cells with low ERβ were insensitive to diosmetin. Knockdown of ERβ confirmed resistance whereas overexpression enhanced sensitivity to diosmetin; which was demonstrated to be mediated by ROS signaling.  In summary, these studies highlight targeting of ERβ with diosmetin as a potential novel therapeutic strategy for the treatment of AML.

http://ift.tt/2g76cb3

EZH2 inhibition by tazemetostat results in altered dependency on B-cell activation signaling in DLBCL

The EZH2 small molecule inhibitor tazemetostat (EPZ-6438) is currently being evaluated in phase II clinical trials for the treatment of non-Hodgkin's Lymphoma (NHL).  We have previously shown that EZH2 inhibitors display an anti-proliferative effect in multiple pre-clinical models of NHL, and that models bearing gain-of-function mutations in EZH2 were consistently more sensitive to EZH2 inhibition than lymphomas with wild-type (WT) EZH2. Here, we demonstrate that cell lines bearing EZH2 mutations show a cytotoxic response, while cell lines with WT-EZH2 show a cytostatic response and only tumor growth inhibition without regression in a xenograft model.  Previous work has demonstrated that co-treatment with tazemetostat and glucocorticoid receptor agonists lead to a synergistic anti-proliferative effect in both mutant and wild-type backgrounds, which may provide clues to the mechanism of action of EZH2 inhibition in WT-EZH2 models.  Multiple agents that inhibit the B-cell receptor pathway (e.g. ibrutinib) were found to have synergistic benefit when combined with tazemetostat in both mutant and WT- EZH2 backgrounds of diffuse large B-Cell Lymphomas (DLBCL). The relationship between B-cell activation and EZH2 inhibition is consistent with the proposed role of EZH2 in B-cell maturation.  To further support this, we observe that cell lines treated with tazemetostat show an increase in the B-cell maturation regulator, PRDM1/BLIMP1 and gene signatures corresponding to more advanced stages of maturation.  These findings suggest that EZH2 inhibition in both mutant and wild-type backgrounds leads to increased B-cell maturation and a greater dependence on B-cell activation signaling.

http://ift.tt/2isFMBr

Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers

Immunotherapy induces durable responses in a subset of patients with cancer. High TMB may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non-small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. We reviewed data on 1,638 patients who had undergone comprehensive genomic profiling and had TMB assessment. Immunotherapy-treated patients (N = 151) were analyzed for response rate (RR), progression-free and overall survival (PFS, OS). Higher TMB was independently associated with better outcome parameters (multivariable analysis). The RR for patients with high (≥ 20 mutations/mb) vs. low to intermediate TMB was 22/38 (58%) vs. 23/113 (20%) (P = 0.0001); median PFS, 12.8 vs. 3.3 months (P = <0.0001); median OS, not reached vs. 16.3 months (P = 0.0036) (Table). Results were similar when anti-PD-1/PD-L1 monotherapy was analyzed (N = 102 patients), with a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders vs. non-responders treated with anti-PD-1/PD-L1 monotherapy was 18.0 vs. 5.0 mutations/mb (P < 0.0001). Interestingly, anti-CTLA4/anti-PD-1/PD-L1 combinations vs. anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%) (P = 0.004) and PFS (P = 0.024). Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. Benefit from dual checkpoint blockade did not show a similarly strong dependence on TMB.

http://ift.tt/2g66yit

Adjuvant radiotherapy after radical cystectomy and ileal orthotopic neobladder

Publication date: Available online 23 August 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Mohmed S. Zaghloul, Tarek M. Zaghloul




http://ift.tt/2isFLgT

Preoperative radiotherapy improves survival in rectal signet-ring cell carcinoma-a population-based study

To investigate the clinical value of preoperative and postoperative radiotherapy (RT) in patients with rectal signet-ring cell carcinoma (SRCC).

http://ift.tt/2xugl57

A pilot study to assess near infrared laparoscopy with indocyanine green (ICG) for intraoperative sentinel lymph node mapping in early colon cancer

Publication date: Available online 23 August 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Andrew C. Currie, Adela Brigic, Siwan Thomas-Gibson, Noriko Suzuki, Morgan Moorghen, John T. Jenkins, Omar D. Faiz, Robin H. Kennedy
BackgroundPrevious attempts at sentinel lymph node (SLN) mapping in colon cancer have been compromised by ineffective tracers and the inclusion of advanced disease. This study evaluated the feasibility of fluorescence detection of SLNs with indocyanine green (ICG) for lymphatic mapping in T1/T2 clinically staged colonic malignancy.MethodsConsecutive patients with clinical T1/T2 stage colon cancer underwent endoscopic peritumoral submucosal injection of indocyanine green (ICG) for fluorescence detection of SLN using a near-infrared (NIR) camera. All patients underwent laparoscopic complete mesocolic excision surgery. Detection rate and sensitivity of the NIR-ICG technique were the study endpoints.ResultsThirty patients (mean age = 68 years [range = 38-80], mean BMI = 26.2 (IQR = 24.7-28.6) were studied. Mesocolic sentinel nodes (median= 3/patient) were detected by fluorescence within the standard resection field in 27/30 patients. Overall, ten patients had lymph node metastases, with one of these patients having a failed SLN procedure. Of the 27 patients with completed SLN mapping, nine patients had histologically positive lymph nodes containing malignancy. 3/9 had positive SLNs with 6 false negatives. In five of these false negative patients, tumours were larger than 35mm with four also being T3/T4.ConclusionICG mapping with NIR fluorescence allowed mesenteric detection of SLNs in clinical T1/T2 stage colonic cancer.ClinicalTrials.gov ID: NCT01662752.



http://ift.tt/2irFnPT

Hypofractionated radiation therapy for basal and squamous cell skin cancer: A meta-analysis

To characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell cancers (BCCs/SCCs).

http://ift.tt/2wzuUYH

Residual tumour hypoxia in head-and-neck cancer patients undergoing primary radiochemotherapy, final results of a prospective trial on repeat FMISO-PET imaging

Hypoxia is a well recognised parameter of tumour resistance to radiotherapy, a number of anticancer drugs and potentially immunotherapy. In a previously published exploration cohort of 25 head and neck squamous cell carcinoma (HNSCC) patients on [18F]fluoromisonidazole positron emission tomography (FMISO-PET) we identified residual tumour hypoxia during radiochemotherapy, not before start of treatment, as the driving mechanism of hypoxia-mediated therapy resistance. Several quantitative FMISO-PET parameters were identified as potential prognostic biomarkers.

http://ift.tt/2xu0qUE

Intermediate-term outcome after PSMA-PET guided high-dose radiotherapy of recurrent high-risk prostate cancer patients

By the use of PSMA positron emission tomography (PET) detection of prostate cancer lesions with a high sensitivity and specificity combined with a favorable lesion to background contrast is feasible. Therefore...

http://ift.tt/2vfRLUW

Neratinib Approved by FDA for HER2-Positive Breast Cancer

FDA has approved neratinib for patients with early-stage HER2-positive breast cancer who have finished at least 1 year of adjuvant therapy with trastuzumab.

http://ift.tt/2wFDF2L

Paradoxical worsening of hypoxemia in a patient treated by noninvasive positive pressure ventilation for obesity hypoventilation syndrome with concomitant obstructive sleep apnea: a case report

Noninvasive positive pressure ventilation is frequently prescribed to obese patients with obstructive sleep apnea syndrome and obesity hypoventilation syndrome. However, mechanical ventilation with a positive ...

http://ift.tt/2wFTINQ

Are heart toxicities in breast cancer patients important for radiation oncologists? A practice pattern survey in German speaking countries

Abstract

Background

To assess the personal beliefs of radiation oncologists regarding heart sparing techniques in breast cancer patients.

Methods

Between August 2015 and September 2015, a survey was sent to radiation oncology departments in Germany, Austria and Switzerland. 82 radiation oncology departments answered the questionnaire: 16 university clinics and 66 other departments. Most (87.2%) of the participants had >10 years of radiation oncology experience.

Results

89.2% of the participants felt that there is enough evidence to support heart sparing for breast cancer patients. The most important dose parameter was considered the mean heart dose (69.1%). The personal "safe" dose to the heart was considered to be 5 Gy (range: 0–40 Gy). The main impediment in offering all breast cancer patients heart-sparing techniques seems to be the fact that these techniques are time/ resource consuming (46.5% of the participants).

Conclusions

Most radiation oncologists believe that there is enough evidence to support heart sparing for breast cancer patients. But translating this belief into a wide practice will need better dosimetric and clinical data on what patients are expected to profit most, specific guidelines for which patients' heart sparing techniques should be performed, as well as recognition of the time/resource consumption of these techniques.

http://ift.tt/2g5Jale

Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial

Abstract

Background

Previous studies have investigated the protective effect of vitamin D serum levels, at diagnosis and during the follow-up period after treatment, on melanoma outcome. In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor.

Methods/design

This study is a multicenter randomized double blind placebo- controlled phase III trial. Patients between the age of 18 and 80 years diagnosed and treated surgically for a melanoma stage IB-III are eligible for randomization in a 1:1 ratio to active treatment or placebo. The study drug is taken each month and consists of either 100,000 International Unit cholecalciferol or arachidis oleum raffinatum used as a placebo. The primary endpoint is relapse free survival. The secondary endpoints are 25 hydroxyvitamin D3 serum levels at diagnosis and at 6 month intervals, melanoma subtype, melanoma site and stage of melanoma at diagnosis according to the 2009 American Joint Committee on Cancer melanoma staging and classification. At randomization a bloodsample is taken for DNA analysis. The study is approved by the local Ethics Committees.

Discussion

If we can confirm our hypothesis that vitamin D supplementation after removal of the tumor has a protective effect on relapse of cutaneous malignant melanoma we may reduce the burden of CMM at several levels. Patients, diagnosed with melanoma may have a better clinical outcome and improved quality of life. There will be a decrease in health care costs related to treatment of metastatic disease and there will be a decrease in loss of professional years, which will markedly reduce the economic burden of the disease.

Trial registration

Clinical Trial.gov, NCT01748448, 05/12/2012

http://ift.tt/2iqPWTn

Clinical decision-making and health-related quality of life during first-line and maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC): findings from a real-world setting

Abstract

Background

Maintenance therapy (MT) with pemetrexed has been shown to improve overall and progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC), without impairing patients' health-related quality of life (HRQOL) substantially. Comprehensive data on HRQOL under real-life conditions are necessary to enable informed decision-making. This study aims to (1) assess HRQOL during first-line chemotherapy and subsequent MT and (2) record patients' and physicians' reasons leading to clinical decisions on MT.

Methods

Patients treated for NSCLC at three Austrian medical centres were included. HRQOL was assessed at every chemotherapy cycle using the EORTC QLQ-C30/+LC13 questionnaire. Semi-structured interviews were conducted before MT initiation and at the time of discontinuation to evaluate patients' and physicians' reasons for treatment decisions. Longitudinal QOL analysis was based on linear mixed models.

Results

Sixty-one (73%) out of 84 patients were considered for MT. Thirty-six patients (43%) received MT and 29 (35%) discontinued therapy. Decisions on MT initiation (in 20 cases by the physician vs 4 by the patient) and discontinuation (19 vs 10) were mainly voiced by the physician. Treatment toxicity of first-line chemotherapy was the main reason for rejection of MT in patients with stable disease and was more often indicated by patients than clinicians. HRQOL data were collected from 83 patients at 422 assessment time points and indicated significantly lower symptom severity during MT compared with first-line therapy for nausea and vomiting (p = 0.006), sleep disturbances (p < 0.001), appetite loss (p = 0.043), constipation (p = 0.017) and chest pain (p = 0.022), and a deterioration in emotional functioning (p = 0.023) and cognitive functioning (p = 0.044) during MT.

Conclusions

Our results indicate that HRQOL and symptom burden improve between first-line treatment to MT in some respects, although some late toxicity persists. Discrepancies between patients' and physicians' perception of reasons for rejecting MT were evident. Thus, the integration of patient-reported outcomes, such as HRQOL, is required to enable shared decision-making and personalised healthcare based on mutual understanding of treatment objectives.

http://ift.tt/2irsx44

New classification for the thoracic paraaortic lymph nodes of patients with esophageal squamous cell carcinoma

Abstract

Purpose

To create a new classification for the thoracic paraaortic lymph nodes (No. 112ao) of patients with esophageal squamous cell carcinoma (ESCC). Classification of these nodes in ESCC patients has been the focus of very few reports.

Methods

The subjects of this study were 27 patients with positive No. 112ao nodes on computed tomography (CT) images before treatment. We divided the No. 112ao nodes into No. 112aoA, located on the esophageal side as anterior No. 112ao nodes, and No. 112aoP, located on the opposite side of the esophagus as posterior No. 112ao nodes. We examined the association between No. 112aoA and No. 112aoP and clinicopathological factors. Recurrence-free survival (RFS) was compared between the No. 112aoA- and No. 112aoP-positive groups.

Results

There were 12 patients in the No. 112aoA-positive group and 15 patients in the No. 112aoP-positive group. The No. 112aoP-positive group had significantly worse RFS than the No. 112aoA-positive group (p = 0.004). Cox multivariate analysis of RFS revealed that No. 112aoP positivity was an independent prognostic factor (p = 0.043).

Conclusions

Our new classification of No. 112ao nodes into No. 112aoA and No. 112aoP is useful clinically. No. 112aoP could correspond to the clinical N4 category of patients with ESCC.

http://ift.tt/2votDyF

The prognostic significance of inflammation-based markers in patients with recurrent gastric cancer

Abstract

Purpose

The aim of this study was to evaluate the prognostic impact of inflammation-based markers, including the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI), in patients with recurrent gastric cancer (RGC).

Methods

This study reviewed 167 patients with RGC. A receiver operating characteristics (ROC) curve analysis was performed to determine the NLR and PNI cutoff values. The prognostic significance of the NLR and PNI was evaluated by a multivariate analysis.

Results

The optimal NLR and PNI cutoff values for predicting the 1-year survival after recurrence were 2.2 and 47, respectively. A univariate analysis revealed that the NLR (p < 0.001) and PNI (p < 0.001) were significantly associated with the survival time after recurrence, along with the histology, peritoneal recurrence, carbohydrate antigen 19-9, and chemotherapy for recurrence. In the multivariate analysis, a higher NLR (p < 0.001) and a lower PNI (p = 0.002) were independent predictors of a shorter survival time. Among the patients who underwent chemotherapy, the NLR and PNI were also independent prognostic factors.

Conclusions

Inflammation-based markers, including the NLR and PNI, are simple and useful clinical biomarkers that can be used to predict the survival time of patients with RGC.

http://ift.tt/2v5gsrf

Cancers, Vol. 9, Pages 110: Integrins as Therapeutic Targets: Successes and Cancers

Cancers, Vol. 9, Pages 110: Integrins as Therapeutic Targets: Successes and Cancers

Cancers doi: 10.3390/cancers9090110

Authors: Sabine Raab-Westphal John Marshall Simon Goodman

Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we examine the current developments in integrin therapeutics, especially in cancer, and comment on the health economic implications of these developments.

http://ift.tt/2v5GMRW

Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma

Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma

British Journal of Cancer 117, 717 (22 August 2017). doi:10.1038/bjc.2017.228

Authors: Hiroaki Itamochi, Tetsuro Oishi, Nao Oumi, Satoshi Takeuchi, Kosuke Yoshihara, Mikio Mikami, Nobuo Yaegashi, Yasuhisa Terao, Kazuhiro Takehara, Kimio Ushijima, Hidemichi Watari, Daisuke Aoki, Tadashi Kimura, Toshiaki Nakamura, Yoshihito Yokoyama, Junzo Kigawa & Toru Sugiyama

http://ift.tt/2uNTnZv

Knowledge or noise? Making sense of General Practitioners’ and Consultant use of 2-week-wait referrals for suspected cancer

Knowledge or noise? Making sense of General Practitioners' and Consultant use of 2-week-wait referrals for suspected cancer

British Journal of Cancer 117, 597 (22 August 2017). doi:10.1038/bjc.2017.213

Authors: Conan Donnelly, Nigel Hart, Alan David McCrorie, Lesley Anderson, Michael Donnelly, Peter Murchie & Anna Gavin

http://ift.tt/2u38Y2I

Long-term outcomes of patients with 10 or more colorectal liver metastases

Long-term outcomes of patients with 10 or more colorectal liver metastases

British Journal of Cancer 117, 604 (22 August 2017). doi:10.1038/bjc.2017.218

Authors: M A Allard, R Adam, F Giuliante, R Lapointe, C Hubert, J N M Ijzermans, D F Mirza, D Elias, C Laurent, T Gruenberger, G Poston, C Letoublon, H Isoniemi, V Lucidi, I Popescu & J Figueras

http://ift.tt/2uO8Ys2

Leukocyte telomere length and renal cell carcinoma survival in two studies

Leukocyte telomere length and renal cell carcinoma survival in two studies

British Journal of Cancer 117, 752 (22 August 2017). doi:10.1038/bjc.2017.237

Authors: Catherine L Callahan, Kendra Schwartz, Julie J Ruterbusch, Brian Shuch, Barry I Graubard, Qing Lan, Richard Cawthon, Andrea A Baccarelli, Wong-Ho Chow, Nathaniel Rothman, Jonathan N Hofmann & Mark P Purdue

http://ift.tt/2v5S1t7

Hamburg-Glasgow classification: preoperative staging by combination of disseminated tumour load and systemic inflammation in oesophageal carcinoma

Hamburg-Glasgow classification: preoperative staging by combination of disseminated tumour load and systemic inflammation in oesophageal carcinoma

British Journal of Cancer 117, 612 (22 August 2017). doi:10.1038/bjc.2017.219

Authors: Matthias Reeh, Tarik Ghadban, Faik G Uzunoglu, Michael F Nentwich, Maximilian Bockhorn, Klaus Pantel, Jakob R Izbicki & Yogesh K Vashist

http://ift.tt/2uXlWRb

Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients

Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients

British Journal of Cancer 117, 704 (22 August 2017). doi:10.1038/bjc.2017.215

Authors: Anne Winther-Larsen, Christina Demuth, Joan Fledelius, Anne Tranberg Madsen, Karin Hjorthaug, Peter Meldgaard & Boe Sandahl Sorensen

http://ift.tt/2tXGoEn

The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

British Journal of Cancer 117, 619 (22 August 2017). doi:10.1038/bjc.2017.222

Authors: Usha Menon, Alistair J McGuire, Maria Raikou, Andy Ryan, Susan K Davies, Matthew Burnell, Aleksandra Gentry-Maharaj, Jatinderpal K Kalsi, Naveena Singh, Nazar N Amso, Derek Cruickshank, Stephen Dobbs, Keith Godfrey, Jonathan Herod, Simon Leeson, Tim Mould, John Murdoch, David Oram, Ian Scott, Mourad W Seif, Karin Williamson, Robert Woolas, Lesley Fallowfield, Stuart Campbell, Steven J Skates, Mahesh Parmar & Ian J Jacobs

http://ift.tt/2vYzJGP

Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium

Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium

British Journal of Cancer 117, 734 (22 August 2017). doi:10.1038/bjc.2017.231

Authors: Artitaya Lophatananon, Sarah Stewart-Brown, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch Garcia, David E Neal, Freddie C Hamdy, Jenny L Donovan, Graham G Giles, Liesel M Fitzgerald, Melissa C Southey, Paul Pharoah, Nora Pashayan, Henrik Gronberg, Fredrik Wiklund, Markus Aly, Janet L Stanford, Hermann Brenner, Aida K Dieffenbach, Volker Arndt, Jong Y Park, Hui-Yi Lin, Thomas Sellers, Chavdar Slavov, Radka Kaneva, Vanio Mitev, Jyotsna Batra, Amanda Spurdle, Judith A Clements, APCB BioResource, The PRACTICAL consortium, Douglas Easton, Rosalind A Eeles & Kenneth Muir

http://ift.tt/2tXoeyJ

Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models

Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models

British Journal of Cancer 117, 628 (22 August 2017). doi:10.1038/bjc.2017.205

Authors: Cristina Belgiovine, Ezia Bello, Manuela Liguori, Ilaria Craparotta, Laura Mannarino, Lara Paracchini, Luca Beltrame, Sergio Marchini, Carlos M Galmarini, Alberto Mantovani, Roberta Frapolli, Paola Allavena & Maurizio D'Incalci

http://ift.tt/2tXc64r

The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer

The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer

British Journal of Cancer 117, e2 (22 August 2017). doi:10.1038/bjc.2017.203

Authors: C B Lajer, E Garnæs, L Friis-Hansen, B Norrild, M H Therkildsen, M Glud, M Rossing, H Lajer, D Svane, L Skotte, L Specht, C Buchwald & F C Nielsen

http://ift.tt/2uXOvxO

HMGA1 expression levels are elevated in pancreatic intraepithelial neoplasia cells in the Ptf1a-Cre; LSL-KrasG12D transgenic mouse model of pancreatic cancer

HMGA1 expression levels are elevated in pancreatic intraepithelial neoplasia cells in the Ptf1a-Cre; LSL-KrasG12D transgenic mouse model of pancreatic cancer

British Journal of Cancer 117, 639 (22 August 2017). doi:10.1038/bjc.2017.216

Authors: Michelle J Veite-Schmahl, William C Joesten & Michael A Kennedy

http://ift.tt/2ufEbnB

Platelet releasate promotes breast cancer growth and angiogenesis via VEGF–integrin cooperative signalling

Platelet releasate promotes breast cancer growth and angiogenesis via VEGF–integrin cooperative signalling

British Journal of Cancer 117, 695 (22 August 2017). doi:10.1038/bjc.2017.214

Authors: Lei Jiang, Yun Luan, Xinyan Miao, Chao Sun, Kailin Li, Zhangsen Huang, Dawei Xu, Mingxiang Zhang, Feng Kong & Nailin Li

http://ift.tt/2uOqo4F

Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients

Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients

British Journal of Cancer 117, 648 (22 August 2017). doi:10.1038/bjc.2017.225

Authors: Roopma Wadhwa, Xuemei Wang, Veerabhadran Baladandayuthapani, Bin Liu, Hironori Shiozaki, Yusuke Shimodaira, Quan Lin, Elena Elimova, Wayne L Hofstetter, Stephen G Swisher, David C Rice, Dipen M Maru, Neda Kalhor, Manoop S Bhutani, Brian Weston, Jeffrey H Lee, Heath D Skinner, Ailing W Scott, Dilsa Mizrak Kaya, Kazuto Harada, Donald Berry, Shumei Song & Jaffer A Ajani

http://ift.tt/2voTqYX

A comparative study of germline BRCA1 and BRCA2 mutation screening methods in use in 20 European clinical diagnostic laboratories

A comparative study of germline BRCA1 and BRCA2 mutation screening methods in use in 20 European clinical diagnostic laboratories

British Journal of Cancer 117, 710 (22 August 2017). doi:10.1038/bjc.2017.223

Authors: Gillian Ellison, Andrew Wallace, Alexander Kohlmann & Simon Patton

http://ift.tt/2tOgsLr

TCTP as a therapeutic target in melanoma treatment

TCTP as a therapeutic target in melanoma treatment

British Journal of Cancer 117, 656 (22 August 2017). doi:10.1038/bjc.2017.230

Authors: M Boia-Ferreira, A B Basílio, A E Hamasaki, F H Matsubara, M H Appel, C R V Da Costa, R Amson, A Telerman, O M Chaim, S S Veiga & A Senff-Ribeiro

http://ift.tt/2u3iEKB

Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma

Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma

British Journal of Cancer 117, 725 (22 August 2017). doi:10.1038/bjc.2017.233

Authors: Sarah Schumacher, Christoph Bartenhagen, Martin Hoffmann, Daniel Will, Johannes C Fischer, Stephan E Baldus, Christian Vay, Georg Fluegen, Levent Dizdar, Daniel Vallböhmer, Christoph A Klein, Wolfram T Knoefel, Nikolas H Stoecklein & Birte Möhlendick

http://ift.tt/2uOoYdJ

A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours

A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours

British Journal of Cancer 117, 666 (22 August 2017). doi:10.1038/bjc.2017.199

Authors: Matthew R Russell, Ciaren Graham, Alfonsina D'Amato, Aleksandra Gentry-Maharaj, Andy Ryan, Jatinderpal K Kalsi, Carol Ainley, Anthony D Whetton, Usha Menon, Ian Jacobs & Robert L J Graham

http://ift.tt/2sWQbJ1

Lung cancer prognostic index: a risk score to predict overall survival after the diagnosis of non-small-cell lung cancer

Lung cancer prognostic index: a risk score to predict overall survival after the diagnosis of non-small-cell lung cancer

British Journal of Cancer 117, 744 (22 August 2017). doi:10.1038/bjc.2017.232

Authors: Marliese Alexander, Rory Wolfe, David Ball, Matthew Conron, Robert G Stirling, Benjamin Solomon, Michael MacManus, Ann Officer, Sameer Karnam, Kate Burbury & Sue M Evans

http://ift.tt/2vpI9HU

RBM38 is involved in TGF-β-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer

RBM38 is involved in TGF-β-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer

British Journal of Cancer 117, 675 (22 August 2017). doi:10.1038/bjc.2017.204

Authors: Jing Wu, Xu-Jie Zhou, Xi Sun, Tian-Song Xia, Xiao-Xia Li, Liang Shi, Lei Zhu, Wen-Bin Zhou, Ji-Fu Wei & Qiang Ding

http://ift.tt/2uwCSxM

Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer

Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer

British Journal of Cancer 117, e1 (22 August 2017). doi:10.1038/bjc.2017.80

Authors: A Kenneth MacLeod, Lourdes Acosta-Jimenez, Philip J Coates, Michael McMahon, Frank A Carey, Tadashi Honda, John D Hayes, Colin J Henderson & C Roland Wolf

http://ift.tt/2o2pH3t

Thyrotoxicosis and Choledocholithiasis Masquerading as Thyroid Storm

A 26-year-old female, thirteen months postpartum, presented to the emergency department for four weeks of epigastric abdominal pain, pruritus, new onset jaundice, and 11.3 kgs (25 lbs) unintentional weight loss. On examination, she was afebrile, tachycardic, alert, and oriented and had jaundice with scleral icterus. Labs were significant for undetectable TSH, FT4 that was too high to measure, and elevated total bilirubin, direct bilirubin, alkaline phosphatase, and transaminases. Abdominal ultrasound revealed cholelithiasis without biliary ductal dilation. Treatment for presumed thyroid storm was initiated. Further work-up with magnetic resonance cholangiopancreatography (MRCP) revealed an obstructing cholelith within the distal common bile duct. With the presence of choledocholithiasis explaining the jaundice and abdominal pain, plus the absence of CNS alterations, the diagnosis of thyroid storm was revised to thyrotoxicosis complicated by choledocholithiasis. Endoscopic retrograde cholangiopancreatogram (ERCP) with sphincterotomy was performed to alleviate the biliary obstruction, with prompt symptomatic improvement. Thyroid storm is a rare manifestation of hyperthyroidism with a high rate of morbidity and mortality. The diagnosis of thyroid storm is based on clinical examination, and abnormal thyroid function tests do not correlate with disease severity. Knowledge of the many manifestations of thyroid storm will facilitate a quick and accurate diagnosis and treatment.

http://ift.tt/2vf28IC

Molecular study of ABCB1 gene and its correlation with imatinib response in chronic myeloid leukemia

Abstract

Purpose

The introduction and success of imatinib mesylate have become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, despite its high efficiency, resistance to imatinib has emerged as a significant problem, which may in part be caused by pharmacogenetic variability. Three single-nucleotide polymorphisms (C1236T, G2677T/A, C3435T) and/or mRNA expression changes of ABCB1 gene were demonstrated to be associated with inter-individual variability of imatinib response in CML patients. In this study, we aimed to examine whether genetic variations and/or altered expression of ABCB1 gene may influence response to imatinib.

Methods

Sixty nine CML Tunisian patients, undergoing imatinib therapy, were enrolled in this study. These were divided into two groups: responders and non-responders to imatinib. The relative transcript expression levels of ABCB1 gene and the distribution of allele and genotype frequency of ABCB1 SNPs were compared between these two categories of patients. Linkage disequilibrium tests and haplotypes analysis were also studied.

Results

Our results showed that the mRNA expression level of ABCB1 gene did not differ significantly between the two categories of patients. In addition, results obtained from ABCB1 polymorphisms study and their correlation with imatinib response showed that the optimal response rate to imatinib did not differ significantly between C1236T, G2677T/A or C3435T genotypes. However, haplotype analysis showed that the 1236C–2677A–3435C haplotype was observed only in imatinib non-responders' patients suggesting that CAC haplotype was linked to higher risk of imatinib resistance.

Conclusion

Furthermore, analyses of ABCB1 haplotypes should be taken into account to study the relationship between ABCB1 genotypes and imatinib efficacy.

http://ift.tt/2wEHR2N

Diagnostic value of prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) for early stage HBV related hepatocellular carcinoma

Abstract

Background

To evaluate the diagnostic efficacy of prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) for early stage hepatitis virus B (HBV) related hepatocellular carcinoma (HCC).

Methods

Serums levels of PIVKA-II and a-Fetoprotein (AFP) was detected and compared in 113 patients with clinical confirmed Barcelona Clinic Liver Cancer (BCLC) stage 0-A HBV-related HCC and 161 chronic hepatitis B (CHB) patients. Diagnostic efficiencies as well as cut-off values of PIVKA-II, AFP and combination of the two markers were calculated using receiver operator curve (ROC) analysis.

Results

The mean level of PIVKA-II among HCC patients were 79.64 ± 149.88, significantly higher than control group (P < 0.001). ROC results showed that among those AFP-negative HCC patients, the area under ROC curve (AUROC) of PIVKA-II was 0.73 (95%CI 0.640–0.815, P < 0.001). Among HCC patients diagnosed with small HCC (tumor size ≤2 cm), the AUROC of PIVKA- II was 0.692 (95%CI 0.597–0.788, P < 0.001). To evaluate the diagnostic value of PIVKA-II in HCC patient, all CHB cases were pooled together as control for analysis. The AUROC of PIVKA-II was 0.756 (95%CI 0.698–0.814, P < 0.001), and the optimal cutoff value of PIVKA-II was 32.09 mAU/ml with sensitivity of 52.21% and specificity of 81.49%. When serum levels of PIVKA-II and AFP were combined to obtain a new marker for HCC diagnosis, PIVKA-II + AFP further increased diagnostic efficiency, with AUROC of 0.868 (95%CI 0.822–0.913), higher than that of AFP (P < 0.01) or PIVKA-II (P < 0.001) alone. In addition, we found that HCC patients in poorly differentiated- undifferentiated group and in microvascular invasion group had higher levels of PIVKA-II. Multivariate analysis showed that high serum PIVKA-II level (OR = 1.003, 95%CI 1.001–1.007, P = 0.047) was an independent risk factor for microvascular invasion in HCC patients.

Conclusion

Serum PIVKA-II level is a potential marker for early diagnosis of HCC and microvascular invasion. The use of PIVKA-II may improve assessment of tumor prognosis and guide development of therapeutic strategy.

http://ift.tt/2v5wPUJ

A parallel-group randomized clinical trial of individually tailored, multidisciplinary, palliative rehabilitation for patients with newly diagnosed advanced cancer: the Pal-Rehab study protocol

Abstract

Background

The effect of early palliative care and rehabilitation on the quality of life of patients with advanced cancer has been only sparsely described and needs further investigation. In the present trial we combine elements of early, specialized palliative care with cancer rehabilitation in a 12-week individually tailored, palliative rehabilitation program initiated shortly after a diagnosis of advanced cancer.

Methods

This single center, randomized, controlled trial will include 300 patients with newly diagnosed advanced cancer recruited from the Department of Oncology, Vejle Hospital. The patients are randomized to a specialized palliative rehabilitation intervention integrated in standard oncology care or to standard oncology care alone. The intervention consists of a multidisciplinary group program, individual consultations, or a combination of both. At baseline and after six and 12 weeks the patients will be asked to fill out questionnaires on symptoms, quality of life, and symptoms of depression and anxiety. Among the symptoms and problems assessed, patients are asked to indicate the problem they need help with to the largest extent. The effect of the intervention on this problem is the primary outcome measure of the study. Secondary outcome measures include survival and economic consequences.

Discussion

To our knowledge the Pal-Rehab study is the first randomized, controlled, phase III trial to evaluate individually tailored, palliative rehabilitation in standard oncology care initiated shortly after an advanced cancer diagnosis. The study will contribute with evidence on the effectiveness of implementing early palliative care in standard oncology treatment and hopefully offer new knowledge and future directions as to the content of palliative rehabilitation programs.

Trial Registration

Clinicaltrials.gov Identifier: NCT02332317, registered retrospectively on December 30, 2014. One study participant had been enrolled at the time.

http://ift.tt/2w2Y2Vj

Development of nomograms to predict axillary lymph node status in breast cancer patients

Abstract

Background

Prediction of axillary lymph node (ALN) status preoperatively is critical in the management of breast cancer patients. This study aims to develop a new set of nomograms to accurately predict ALN status.

Methods

We searched the National Cancer Database to identify eligible female breast cancer patients with profiles containing critical information. Patients diagnosed in 2010–2011 and 2012–2013 were designated the training (n = 99,618) and validation (n = 101,834) cohorts, respectively. We used binary logistic regression to investigate risk factors for ALN status and to develop a new set of nomograms to determine the probability of having any positive ALNs and N2–3 disease. We used ROC analysis and calibration plots to assess the discriminative ability and accuracy of the nomograms, respectively.

Results

In the training cohort, we identified age, quadrant of the tumor, tumor size, histology, ER, PR, HER2, tumor grade and lymphovascular invasion as significant predictors of ALNs status. Nomogram-A was developed to predict the probability of having any positive ALNs (P_any) in the full population with a C-index of 0.788 and 0.786 in the training and validation cohorts, respectively. In patients with positive ALNs, Nomogram-B was developed to predict the conditional probability of having N2–3 disease (P_con) with a C-index of 0.680 and 0.677 in the training and validation cohorts, respectively. The absolute probability of having N2–3 disease can be estimated by P_any*P_con. Both of the nomograms were well-calibrated.

Conclusions

We developed a set of nomograms to predict the ALN status in breast cancer patients.

http://ift.tt/2w3n4U7

Ageing, exposure to pollution, and interactions between climate change and local seasons as oxidant conditions predicting incident hematologic malignancy at KINSHASA University clinics, Democratic Republic of CONGO (DRC)

Abstract

Background

The global burden of hematologic malignancy (HM) is rapidly rising with aging, exposure to polluted environments, and global and local climate variability all being well-established conditions of oxidative stress. However, there is currently no information on the extent and predictors of HM at Kinshasa University Clinics (KUC), DR Congo (DRC). This study evaluated the impact of bio-clinical factors, exposure to polluted environments, and interactions between global climate changes (EL Nino and La Nina) and local climate (dry and rainy seasons) on the incidence of HM.

Methods

This hospital-based prospective cohort study was conducted at Kinshasa University Clinics in DR Congo. A total of 105 black African adult patients with anaemia between 2009 and 2016 were included. HM was confirmed by morphological typing according to the French-American-British (FAB) Classification System. Gender, age, exposure to traffic pollution and garages/stations, global climate variability (El Nino and La Nina), and local climate (dry and rainy seasons) were potential independent variables to predict incident HM using Cox regression analysis and Kaplan Meier curves.

Results

Out of the total 105 patients, 63 experienced incident HM, with an incidence rate of 60%. After adjusting for gender, HIV/AIDS, and other bio-clinical factors, the most significant independent predictors of HM were age ≥ 55 years (HR = 2.4; 95% CI 1.4–4.3; P = 0.003), exposure to pollution and garages or stations (HR = 4.9; 95% CI 2–12.1; P < 0.001), combined local dry season + La Nina (HR = 4.6; 95%CI 1.8–11.8; P < 0.001), and combined local dry season + El Nino (HR = 4; 95% CI 1.6–9.7; P = 0.004). HM types included acute myeloid leukaemia (28.6% n = 18), multiple myeloma (22.2% n = 14), myelodysplastic syndromes (15.9% n = 10), chronic myeloid leukaemia (15.9% n = 10), chronic lymphoid leukaemia (9.5% n = 6), and acute lymphoid leukaemia (7.9% n = 5). After adjusting for confounders using Cox regression analysis, age ≥ 55 years, exposure to pollution, combined local dry season + La Nina and combined local dry season + El Nino were the most significant predictors of incident hematologic malignancy.

Conclusion

These findings highlight the importance of aging, pollution, the dry season, El Nino and La Nina as related to global warming as determinants of hematologic malignancies among African patients from Kinshasa, DR Congo. Cancer registries in DRC and other African countries will provide more robust database for future researches on haematological malignancies in the region.

http://ift.tt/2wnJnGM

New trend in colorectal cancer in Germany: are young patients at increased risk for advanced colorectal cancer?

Abstract

Background

The role of colonoscopy in the screening of colorectal cancer (CRC) has been unequivocally established. In Germany, screening colonoscopy with full insurance reimbursement is available for individuals aged 55 and above, and/or for persons with well-known risk factors for CRC. However, advanced CRC is not uncommon in individuals below 55 years. This study was designed to investigate the incidence of advanced CRC in patients < 55 years.

Methods

A retrospective analysis of data from a prospectively maintained CRC database of a university hospital in Germany was performed. Using the recommended age for screening colonoscopy as cutoff, the study population was divided into two groups: < 55 years (study group) and ≥ 55 years (control group). Both groups were compared with regard to the extent of CRC using the UICC stages. Only surgically managed patients were included for analysis. Advanced CRC was defined as UICC stage III or IV.

Results

Complete follow-up data was available for 609 patients treated between 2009 and 2013. The study group included 83 patients, 42 females and 41 males with a median age of 48.0 ± 10 years, while the control group was made up of 526 patients, 230 females and 296 males with a median age of 75.5 ± 8.3 years. Both groups were comparable with regard to gender distribution, p = 0.24. Significantly more patients from the study group were diagnosed with advanced CRC in comparison to the control group, 56.6 vs. 43.9%, p = 0.03. There was no statistically significant difference amongst both groups with respect to cancer-related mortality, 10.8 vs. 12.5%, p = 0.66.

Conclusion

Patients below the recommended age for screening colonoscopy might be at increased risk for advanced CRC. There is need to decrease the recommended age for screening colonoscopy to prevent CRC or enable an early diagnosis in patients below 55 years.

http://ift.tt/2veUDl2

Effects of exercise training on patients with lung cancer who underwent lung resection: a meta-analysis

Abstract

Background

The efficacy of exercise training in patients with lung cancer after lung resection has not been well established yet. Therefore, we performed a meta-analysis to investigate the efficiency of exercise training in patients with lung cancer after lung resection.

Methods

Several databases were searched for eligible randomised controlled trials (RCTs). The primary outcome was quality of life, and the secondary outcomes included 6-min walk distance (6MWD), forced expiratory volume in 1 s (FEV₁) and postoperative complications (POCs). Weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated by random-effects model.

Results

Six RCTs involving 438 patients were enrolled in this meta-analysis. The pooled WMDs of the scores were 2.41 (95% CI = −5.20 to 10.02; P = 0.54) and −0.46 (95% CI = −20.52 to 19.61; P = 0.96) for the physical and mental components of the 36-item short-form scale, respectively. The pooled WMDs were 23.50 m (95% CI = −22.04 to 69.03; P = 0.31) for 6MWD and 0.03 L (95% CI = −0.19 to 0.26; P = 0.76) for FEV₁. Finally, the pooled RRs were 0.79 (95% CI = 0.41 to 1.53; P = 0.49) for POCs.

Conclusions

Insufficient evidence is available to support the efficacy of exercise training in patients with lung cancer after lung resection. Further studies must confirm our findings and investigate the long-term effects of exercise training on patients with lung cancer following lung resection.

http://ift.tt/2wEvhRe

Rectal carcinoma and multiple gastrointestinal stromal tumors (GIST) of the small intestine in a patient with neurofibromatosis type 1: a case report

Abstract

Background

Neurofibromatosis type 1 (NF1) is an autosomally dominant inherited disorder characterized by multiple pigmented skin spots (café-au-lait spots) and neurofibroma. NF1 is associated with a wide variety of benign or malignant tumors. We report a NF1 patient who received surgical treatment for rectal carcinoma and multifocal small intestinal gastrointestinal stromal tumors (GISTs).

Case presentation

A 70-year-old female patient with NF1 was referred to our hospital after a positive fecal occult blood test. Locally advanced rectal carcinoma was detected in the upper rectum using colonoscopy. A submucosal tumor 20 mm in diameter was detected in the duodenal bulb during the upper gastrointestinal endoscopy. The biopsy specimen from the duodenum was GIST with positive immunostaining of KIT and CD34 microscopically. Laparoscopic low anterior resection for rectal carcinoma and local excision of the duodenal GIST were performed successfully. During the operation, five white small nodules were found on the serosa of the jejunum. One nodule was excised for histological examination. The resected rectal tumor was a well-differentiated adenocarcinoma with multiple lymph nodes metastases according to the histology. The duodenal tumor was found to be low-risk GIST. Moreover, the nodule from the jejunum was very low risk GIST. An excised skin wart was neurofibroma according to the histology.

Conclusions

GIST or carcinomas have been reported to occasionally occur in the digestive tract of the patients with NF1. We present a rare case of a NF1 patient with GISTs and colorectal carcinoma.

http://ift.tt/2veMM6V

Long-term survival following hepatectomy, radiation, and chemotherapy for recurrent pancreatic carcinoma: a case report

Abstract

Background

Recurrent pancreatic carcinoma (PC) is generally well known to have a poor prognosis. Cases in which multidisciplinary treatments have been remarkably effective are rare.

Case presentation

Herein, we reported a case of long-term survival following a combination of hepatectomy for a liver metastasis and radiation and chemotherapy for abdominal lymph node metastases after a curative pancreaticoduodenectomy for PC. A 51-year-old Japanese man underwent a pancreaticoduodenectomy following a PC diagnosis in December 2011. After the surgery, the patient received 16 cycles of gemcitabine (GEM) adjuvant chemotherapy. Abdominal computed tomography (CT) after therapy with GEM (17 months after surgery) revealed a 1-cm nodule in the liver, for which the patient underwent partial hepatectomy in May 2013. Approximately 1 month after the hepatectomy, the patient underwent adjuvant chemotherapy using tegafur/gimeracil/oteracil (S-1) for 12 months. Approximately 1 year after the second surgery, an abdominal CT scan detected the abdominal lymph node metastases, for which the patient underwent radiation therapy. After the radiation therapy, combination therapy with 5-fluorouracil(5-FU)/leucovorin plus oxaliplatin or irinotecan was started in September 2014; 59 cycles of this chemotherapy have been administered up to the time of this report. At 67 months after the pancreaticoduodenectomy and 50 months after the hepatectomy, the patient has remained healthy with no relapse or recurrent lesions.

Conclusion

We have managed a long-term survivor who underwent hepatectomy for liver metastasis and radiation therapy and chemotherapy for abdominal lymph node metastases after curative pancreaticoduodenectomy for PC.

http://ift.tt/2wE9PM8

Serum biomarkers to predict risk of testicular and penile cancer in AMORIS

Arunangshu Ghoshal, Hans Garmo, Rhonda Arthur, Niklas Hammar, Ingmar Jungner, Håkan Malmström, Mats Lambe, Göran Walldius and Mieke Van Hemelrijck

http://ift.tt/2w2NpC0

Malignant extra-adrenal pelvic paraganglioma in a paediatric patient

Gabriel Cao, Julian Mendez and Daniel Navacchia

http://ift.tt/2wnoMlK

Risk of second primary cancers among patients with a first primary gastric cancer: A population-based study in North Portugal

Publication date: October 2017
Source:Cancer Epidemiology, Volume 50, Part A
Author(s): Samantha Morais, Luís Antunes, Maria José Bento, Nuno Lunet
BackgroundThe growing number of incident cases of gastric cancer along with improved survival result in a rising population of survivors at risk of second primary cancers (SPC). We estimated the cumulative incidence of metachronous (diagnosed >2months after first primary cancer [FPC]) SPC in gastric FPC patients and compared the incidence of metachronous SPC with that expected in the general population.MethodsA cohort of gastric FPC patients from the North Region Cancer Registry of Portugal, diagnosed in 2000–2006 (n=7427) was followed to 31 December 2010 for synchronous and metachronous SPCs. Cumulative incidence of metachronous SPCs taking into account death as a competing event and standardized incidence ratios (SIR) of metachronous SPCs were estimated.ResultsOverall, 331 (4.5%) patients developed an SPC (26.9% synchronous and 73.1% metachronous). Over half of the SPCs occurred in digestive organs. Among men, the most frequent were colon, prostate, and trachea, bronchus and lung; in women, colon, breast and thyroid were the most common. The 10-year cumulative incidence of metachronous SPC for males was 5.7% and for females 3.5%. The SIR for all cancers was 1.30 in males and 1.20 in females. Among both sexes, significantly higher SIRs were observed for cancers of the oesophagus (males: 4.99; females: 8.03), small intestine (males: 11.04; females: 13.09) and colon (males: 2.42; females: 2.58).ConclusionsPatients with a gastric FPC were found to be at increased risk of developing SPC, mainly in digestive organs, when compared to the general population. Close surveillance of these patients may allow early detection of SPC.



http://ift.tt/2vnI4TO

Laparoscopic complete mesocolic excision via mesofascial separation for left-sided colon cancer

Abstract

Purpose

To evaluate the safety and feasibility of laparoscopic complete mesocolic excision (CME) via mesofascial separation for left-sided colon cancer.

Methods

We evaluated prospectively collected data on 65 consecutive patients with stage I–III left-sided colon cancer, who underwent laparoscopic CME between October 2011 and September 2016. After the exclusion of 5 patients who had T4b or other active tumors, 60 patients were the subjects of this analysis. The completeness of CME, preservation of the hypogastric nerve, operative data, pathological findings, complications, and length of hospital stay were assessed.

Results

CME completeness was graded as the mesocolic and intramesocolic plane in 54 and 6 patients, respectively. The hypogastric nerve was preserved in all patients. A total of 17, 12, 28, and 3 patients had T1, T2, T3, and T4a tumors, respectively. The mean number of lymph nodes retrieved was 16.2, and lymph node metastasis was identified in 22 patients. The mean operative time and intraoperative blood loss were 283 min and 38 ml, respectively. One patient had an intraoperative complication and six patients had postoperative complications. The hospital stay was 12 days.

Conclusion

Laparoscopic CME via mesofascial separation is a safe and feasible procedure for left-sided colon cancer.

http://ift.tt/2v5yZn4

Prognostic role of stereotactic body radiation therapy for elderly patients with advanced and medically inoperable pancreatic cancer

Abstract

The role of stereotactic body radiation therapy for the elderly with advanced or medically inoperable pancreatic cancer was still debated. Therefore, we evaluated the value of stereotactic body radiation therapy and its association with survival of those patients. A total of 417 elderly patients were retrospectively reviewed from 2012 to 2015. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and toxicities were analyzed. Prescription doses ranged from 30–46.8 Gy in 5–8 fractions. Median age was 73 years old. Median OS, PFS, LRFS, and DMFS were 10, 8, 10, and 9.5 months, respectively. One-year OS, PFS, LRFS, and DMFS rate were 35.5%, 18.2%, 26.6%, and 27.1%, respectively. Tumor stage and tumor response at 6 months and CA19-9 levels normalization at 3 months after treatment were independent predictors of OS, PFS, LRFS, and DMFS. Patients with early-stage cancer, better tumor response, and normalization of CA19-9 levels had significantly longer OS, PFS, LRFS, and DMFS. Patients with the prodrug of 5-FU and radiotherapy had longer survival than those with gemcitabine-based chemotherapy and radiotherapy. Patients who received BED₁₀ ≥ 60 Gy achieved better tumor response compared with those who received BED₁₀ < 60 Gy. Two patients had grade 4 intestinal strictures. No grade 3 or higher hematologic toxicities occurred. Stereotactic body radiation therapy is safe and effective for elderly patients with advanced or medically inoperable pancreatic cancer. Early efficacy could be predictive of prognosis. Higher doses may be associated with efficacy but need further investigation.

The study demonstrated the feasibility and safety of stereotactic body radiation therapy for elder with locally pancreatic cancer, with acceptable survival and mild toxicities. Besides, higher doses may be associated with better tumor response.

http://ift.tt/2wEmP4n

Combination therapy using molecular-targeted drugs modulates tumor microenvironment and impairs tumor growth in renal cell carcinoma

Abstract

Tumor growth and metastasis are determined not by cancer cells alone but also by a variety of stromal cells, various populations of which overexpress platelet-derived growth factor receptors (PDGF-Rs). In addition, activation of PI3K-AKT-mammalian target of rapamycin (mTOR) signaling is frequently observed in many cancer types as well. mTOR comprises a serine/threonine kinase that increases the production of proteins that stimulate key cellular processes such as cell growth and proliferation, cell metabolism, and angiogenesis. In this study, we investigated the impact of molecular-targeting agents including PDGF-R and mTOR inhibitors on the tumor stroma of human kidney cancer and examined the efficacy of combination therapy with these agents against this disease. Treatment with sunitinib did not suppress tumor growth, but significantly decreased stromal reactivity, microvessel density, and pericyte coverage of tumor microvessels in an orthotopic mouse model. In contrast, treatment with everolimus decreased tumor growth and microvessel density but not stromal reactivity. However, sunitinib and everolimus in combination reduced both the growth rate and stromal reaction. These findings suggest that target molecule-based inhibition of the cancer–stromal cell interaction appears promising as an effective antitumor therapy.

We showed that aTKI inhibits the cancer stroma of RCC mainly through PDGF signaling pathways, whereas an mTOR inhibitor inhibits cancer cell proliferation, such that the combination therapy effectively inhibits the tumor environment of RCC leading to impaired tumor growth.

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Promotion of cell proliferation by the proto-oncogene DEK enhances oral squamous cell carcinogenesis through field cancerization

Abstract

Oral squamous cell carcinoma (OSCC) develops through a multistep carcinogenic process involving field cancerization. The DEK gene is a proto-oncogene with functions in genetic and epigenetic modifications, and has oncogenic functions, including cellular proliferation, differentiation, and senescence. DEK overexpression is associated with malignancies; however, the functional roles of DEK overexpression are unclear. We demonstrated that DEK-expressing cells were significantly increased in human dysplasia/carcinoma in situ and OSCC. Furthermore, we generated ubiquitous and squamous cell-specific doxycycline (DOX)-inducible Dek mice (iDek and iDek-e mice respectively). Both DOX+ iDek and iDek-e mice did not show differences in the oral mucosa compared with DOX- mice. In the environment exposed to carcinogen, DOX-treated (DOX+) iDek mice showed field cancerization and OSCC development. Microarray analysis revealed that DEK overexpression was mediated by the upregulation of DNA replication- and cell cycle-related genes, particularly those related to the G₁/S transition. Tongue tumors overexpressing DEK showed increased proliferating cell nuclear antigen and elongator complex protein 3 expression. Our data suggest that DEK overexpression enhanced carcinogenesis, including field cancerization, in OSCC by stimulating the G₁/S phase transition and promoting DNA replication, providing important insights into the potential applications of DEK as a target in the treatment and prevention of OSCC.

Representative images of IHC analysis for detection of PCNA in the tongues of 4NQO-treated mice with or without DOX (DOX+ and DOX- respectively). Scale bars, 40 μm. PCNA-positive cells in DOX+ iDek mice were spread to the upper layer of the epithelium and the PCNA-positive index in DOX+ iDek mice was significantly higher than that in DOX- iDek mice.

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Digital PCR analysis of circulating tumor DNA: a biomarker for chondrosarcoma diagnosis, prognostication, and residual disease detection

Abstract

Conventional chondrosarcoma is the most common primary bone tumor in adults. Prognosis corresponds with tumor grade but remains variable, especially for individuals with grade (G) II disease. There are currently no biomarkers available for monitoring or prognostication of chondrosarcoma. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for a broad range of tumor types. To date, little has been done to study the presence of ctDNA and its potential utility in the management of sarcomas, including chondrosarcoma. In this study, we have assessed ctDNA levels in a cohort of 71 patients, 32 with sarcoma, including 29 individuals with central chondrosarcoma (CS) and 39 with locally aggressive and benign bone and soft tissue tumors, using digital PCR. In patients with CS, ctDNA was detected in pretreatment samples in 14/29 patients, which showed clear correlation with tumor grade as demonstrated by the detection of ctDNA in all patients with GIII and dedifferentiated disease (n = 6) and in 8/17 patients with GII disease, but never associated with GI CS. Notably detection of ctDNA preoperatively in GII disease was associated with a poor outcome. A total of 14 patients with CS had ctDNA levels assessed at multiple time points and in most patients there was a clear reduction following surgical removal. This research lays the foundation for larger studies to assess the utility of ctDNA for chondrosarcoma diagnosis, prognostication, early detection of residual disease and monitoring disease progression.

Circulating tumor DNA (ctDNA) is emerging as a powerful biomarker for a range of cancers. The authors of this study have used digital PCR to assess the ability to detect ctDNA for the first time in patients with chondrosarcoma. ctDNA was detectable in 14 of 29 patients and its detection was associated with high-grade disease and a significantly poorer prognosis compared to those patients in whom mutant IDH1 was not detected in cell free DNA.

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Preoperative radiotherapy improves survival in rectal signet-ring cell carcinoma-a population-based study

Abstract

Background

To investigate the clinical value of preoperative and postoperative radiotherapy (RT) in patients with rectal signet-ring cell carcinoma (SRCC).

Methods

Using the Surveillance, Epidemiology, and End Results program patients with stage II–III rectal SRCC were retrospectively included between 1988 and 2012. Univariate and multivariate Cox regression analyses were performed to analyze the effect of preoperative and postoperative RT on cause-specific survival (CSS).

Results

A total of 292 patients were included: 138 patients received preoperative RT, 101 patients received postoperative RT, and 53 patients underwent surgery alone. Overall, 5– and 10-year CSS was 43.8 and 37.6%, respectively. Preliminary survival analysis demonstrated that preoperative RT improved CSS versus surgery alone, especially in patients with stage III disease. Multivariate analysis demonstrated that preoperative RT was independent predictors for CSS in stage III rectal SRCC. CSS in preoperative and postoperative RT groups was comparable.

Conclusions

Preoperative RT significantly improved survival outcomes in patients with stage III rectal SRCC.

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A Comparative Study of Clinical Profile and Relapse Patterns in TRIPLE-NEGATIVE and Non - Triple-Negative Breast Cancer Patients Treated with Curative Intent

Abstract

Molecular subtyping in breast cancer is recently emerging as an important determinant of treatment and outcomes, and triple negative breast cancer (TNBC) has been established as a distinct clinical entity with unique features and adverse outcomes. A retrospective analysis of a prospectively maintained computerized breast cancer database was performed, and all the non-metastatic female breast cancer patients undergoing potentially curative multimodality treatment between 2005 and 2012 were included for analysis. Patients with incomplete information regarding ER, PR, and HER2/neu status were excluded. All the eligible patients were divided into TNBC and non-TNBC group based on molecular subtyping. A comparative analysis between the two groups was performed to analyze the clinical spectrum and patterns of relapse. A total of 861 patients qualified for the final analysis and the proportion of TNBC was 254 (29.5%) and non-TNBC was 607 (70.5%). Patients in the TNBC group were slightly younger than the non-TNBC group (median age 46 vs. 49, p value = 0.006). TNBC group had a higher breast conservation surgery (BCS) rate, and there was no difference in the need for chemo and radiotherapy between two groups. The overall recurrence rates were significantly higher in TNBC group compared to non-TNBC group (26.8 vs. 19.3%, p value = 0.01). Local disease recurrences were significantly higher in TNBC compared to non-TNBC (7.9 vs. 3.1%, p value = 0.002). Both the regional and systemic recurrences were higher in TNBC group compared to non-TNBC, though the difference failed to attain statistical significance (for regional recurrences 2.4 vs. 1.5%, p value = 0.36; for systemic recurrences 23.2 vs. 17.8%, p value = 0.06). The brain metastasis was significantly higher in TNBC group (6.7 vs. 3.3%, p value = 0.02). In addition, time to relapse was also significantly less in TNBC cohort (16.1 vs. 22.1 months). TNBC accounts for almost one-third of the breast cancer patients with a relatively younger age at presentation, higher volume of disease burden and high breast conservation rates. Despite a standard multimodality therapy the local, systemic, and CNS recurrence rates are high in TNBC and majority relapse within first 2 years after completion of therapy.

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Salmonella Thompson splenic abscess in a healthy female

A 26-year-old woman presented with a 5-day history of fever and 3-day history of left upper quadrant abdominal pain and cough associated with left shoulder tip pain. Initial blood cultures did not display growth. On CT imaging, there was a cyst measuring 7.2x8 cm originally interpreted to be haemorrhagic in nature. Repeat cultures during admission revealed Salmonella Thompson. Percutaneous drainage and antibiotic treatment, rather than splenectomy, was successfully pursued with the patient afebrile and in no pain at 6 weeks follow-up.

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BRAF Mutation as a Novel Driver of Eosinophilic Cystitis.

BRAF Mutation as a Novel Driver of Eosinophilic Cystitis.

Cancer Biol Ther. 2017 Aug 22;:0

Authors: Choi MY, Tsigelny IF, Boichard A, Skjevik ÅA, Shabaik A, Kurzrock R

Abstract
Eosinophilic cystitis is a rare manifestation of hypereosinophilia and a cause of morbidity, including dysuria and hematuria. Although some cases can be attributed to infection or allergy, most cases are assessed to be idiopathic and treated with corticosteroids. However, hypereosinophilia can also be due to actionable clonal molecular alterations in the hematopoietic cells, similar to other myeloproliferative neoplasms. Common mutations associated with eosonophilic syndromes are of platelet-derived growth factor receptor alpha or beta or c-kit, though other pathogenic mutations have been found by next generation sequencing. Determination of a specific mutation may therefore identify clonality and refine treatment of some cases. Here we review the molecular features of eosinophilic disorders. We also describe the use of a liquid biopsy of circulating cell-free DNA in the workup of of a case of eosinophilic cystitis in which next generation sequencing of cell-free DNA showed a BRAF I463T mutation. In silico modeling supports the functional impact and potential clinical relevance of BRAF I463T.

PMID: 28829677 [PubMed - as supplied by publisher]

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Resolution of Periodic Breathing in a Child with Idiopathic Pulmonary Arterial Hypertension

Central sleep apnea (CSA) and periodic breathing are unusual findings described in pediatric patients with congestive heart failure. However, CSA has not been reported in children with pulmonary hypertension. We hereby report on a 10-year-old girl with idiopathic pulmonary arterial hypertension who had frequent central events in a periodic breathing fashion seen in her polysomnography, which was normalized following medical treatment leading to improvement of the pulmonary pressures.

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Physiotherapy and Rehabilitation in a Child with Joubert Syndrome

Objective. Joubert syndrome (JS) is a rare autosomal recessive genetic disorder characterized by brain malformation, hypotonia, breathing abnormalities, ataxia, oculomotor apraxia, and developmental delay. The purpose of this study was to report the efficiency of the physiotherapy and rehabilitation program in a child with JS. Materials and Methods. Our case is a 19-month-old female child with mild clinical signs of JS. The pretreatment and posttreatment motor functioning level of the case was evaluated through the Gross Motor Function Measure (GMFM), whereas the independence level was evaluated through the Pediatric Functional Independence Measure (WeeFIM). The case was included in the rehabilitation program by the physiotherapist for one hour for five days a week throughout the period of 13 months in accordance with the neurodevelopmental treatment principles. Results. The case was able to turn around from the supine position to the reverse direction by oneself, and she was able to rise on her forearms facedown and was able to sit, crawl, and walk independently. The GMFM score was 210, whereas WeeFIM score was 65. Discussion. In the direction of those findings, in Joubert Syndrome, physiotherapy and rehabilitation can be effective in coping with the symptoms causing developmental delay.

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Modulation of adenylate cyclase signaling in association with MKK3/6 stabilization under combination of SAC and berberine to reduce HepG2 cell survivability

Abstract

Cancer cells often have faulty apoptotic pathways resulting in sustenance of survivability, tumour metastasis and resistance to anticancer drugs. Alternate strategies are sought to improve therapeutic efficacy and therefore HepG2 cells were treated with S-allyl-cysteine (SAC) and berberine (BER) to analyze their mechanistic impact upon necroptosis along with its interacting relationship to apoptosis. In the present study we observed that SAC and BER exposure reduced NFκβ nuclear translocation through adenylate cyclase-cAMP-protein kinaseA axis and eventually evaded c-FLIP inhibition. Effective RIP1 k63-polyubiquitination and persistent MKK3/MKK6 expression during drug treatment potentiated caspase8 activity via p53—DISC conformation. Resultant tBid associated lysosomal protease mediated AIF truncation induced DNA fragmentation and persuaded effector caspase mediated scramblase activation resulting induction of necroptosis in parallel to apoptotic events. SAC+BER effectively reduced Rb-phosphorylation resulting insignificant nuclear E2F presence led to ending of cell proliferation. Therefore necroptosis augmented the drug response and may be targeted alongside cell proliferation inhibition in formation of efficient therapeutics against liver cancer.

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Contralateral cerebral hemoglobin oxygen saturation changes in patients undergoing thoracotomy with general anesthesia with or without paravertebral block: a randomized controlled trial

Abstract

Purpose

Perioperative analgesia during thoracotomy is often achieved by combining paravertebral block (PVB) with general anesthesia (GA). Functional near-infrared spectroscopy (NIRS) can detect changes in cerebral oxygenation resulting from nociceptive stimuli in the awake state or under sedation. We used NIRS to measure changes in cerebral blood flow provoked by thoracotomy incision made under GA and determine how these changes were influenced by supplementation of GA with PVB.

Methods

Thirty-four patients undergoing elective thoracotomy were enrolled. Patients were randomly assigned to a group receiving only GA, or GA combined with PVB (GA + PVB). Changes in cerebral oxygenated hemoglobin (ΔO₂Hb), deoxygenated-Hb (ΔHHb), and total-Hb (ΔtotalHb) were evaluated by NIRS as surgery began.

Results

In the GA group, ΔO₂Hb was significantly higher in the hemisphere contralateral to the side of surgery when the incision was made and 2 min after incision compared with the ipsilateral side (start of surgery, P < 0.01; 2 min, P < 0.05). In contrast, there were no significant changes in the ΔO₂Hb at any of the time points in the GA + PVB group. Comparable with ΔO₂Hb, the concentration of ΔtotalHb was significantly higher in the contralateral hemisphere in the GA group at the start of surgery (P < 0.05).

Conclusions

Changes in the cerebral O₂Hb concentration were detected by NIRS immediately after surgical incision under GA, but not in the presence of a PNB. NIRS could be used to monitor surgical pain. PVB inhibited changes in oxygenation induced by incision-provoked pain.

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Dr. Guy Morgan Hicks, Jr. (1926–2017)

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Osteopontin and vasculogenic mimicry formation are associated with response to neoadjuvant chemotherapy in advanced breast cancer

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Polycystic ovary syndrome with asynchronous bilateral adnexal torsion in a natural cycle

Cases involving polycystic ovaries (PCOs) with adnexal torsion in a natural cycle without ovulation induction are rare, and no reports of such cases have described asynchronous bilateral adnexal torsion. Here, we report a case of PCO syndrome (PCOS) with asynchronous bilateral adnexal torsion in a natural cycle. The patient was a 37-year-old woman with a history of 2 gravidas 1 para. Her primary complaint was left lower abdominal pain. Ultrasonography and MRI identified multiple uterine myomas occupying the pelvis and the left ovary, with oedematous swelling that had moved ventrally to the uterus. She was diagnosed with adnexal torsion and underwent emergency laparoscopic adnexectomy. Nine months after surgery, she experienced right lower abdominal pain. Ultrasonography revealed suspected right adnexal torsion and she underwent emergency surgery. The right ovary was twisted 540° counterclockwise and swollen to 7 cm in size, with partial polycystic changes. She was histopathologically diagnosed with a PCO, and the final diagnosis, which also considered the endocrine test results, was PCOS. In PCOS, adnexal torsion may occur if the swollen ovary moves because of a hysteromyoma or other cause. Accordingly, torsion should be considered during the follow-up of patients with PCOS.

http://ift.tt/2vXCET0

Suspected case of lipoedema in Japanese woman with a characteristic histology in skin biopsy

Description

A 42-year-old Japanese woman with a body mass index of 42, presented with a long history of bilateral swelling of buttocks and lower extremities. The upper trunk, upper extremities and feet were spared of excessive fat deposition without a complete loss of adipose tissues (figure 1), lowering the likelihood of partial lipodystrophy. Physical examination revealed that the edema was dry, hard and non-pitting. Stemmer's sign was negative, and five out of seven criteria for the diagnosis of lipoedema1 were met. A CT scan showed massive circumferential enlargement of subcutaneous tissues with the same CT value as fat, further suggesting the diagnosis of lipoedema (figure 1). Other conditions causing lower-extremity swelling or fat excess were excluded. We performed skin punch biopsy of the right hip (figure 2). Chief pathological findings were as follows: (1) the size of adipocytes was generally...

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Filarial breast lump

Lymphatic filariasis is one of the most debilitating and disfiguring scourges among all diseases. This report presents a case of a woman with recurrent breast nodularity after being previously operated for a suspected breast neoplasm. We would like to highlight the issue of similar clinical presentation of a filarial breast lump and other breast lesions leading to inappropriate therapy.

http://ift.tt/2vXLEHJ

Large pectoral haematoma post-transradial catheterisation: an unusual but avoidable complication

Large pectoral haematoma is an extremely rare complication of transradial catheterisation. Branch or main vessel injury due to luminal passage of guidewires and catheters may lead to bleeding and haematoma formation at adjacent sites along the vessel track. We present a 53-year-old post-transradial catheterisation patient, who complained of chest pain due to right axillary artery branch perforation causing haematoma, which was emergently managed by embolisation with autologous coagulated blood.

http://ift.tt/2xbC6HP

A rare case of pulmonary toxoplasmosis in a patient with undifferentiated inflammatory arthritis on chronic methotrexate and corticosteroid therapy

Pulmonary toxoplasmosis is a serious pulmonary condition caused by the protozoan Toxoplasma gondii. It typically affects immunocompromised patients presenting acutely with cough, fever, myalgias, arthralgias and lymphadenopathy, and chronically with persistent cough and dyspnoea. Because of its protean features, it can mimic many more common lung conditions in the immunocompromised patient, including atypical pneumonia, Pneumocystis pneumonia and interstitial lung disease. In this article, we present the case of a 55-year-old woman who presented to our hospital with persistent dyspnoea and cough, initially suspected to have an arthritis-related interstitial lung disease. She received a final diagnosis of pulmonary toxoplasmosis after lung biopsy demonstrated Toxoplasma cysts, later confirmed by serology. Treatment with trimethoprim–sulfamethoxazole resulted in significant improvement of her respiratory symptoms after 3 months.

http://ift.tt/2vXCECu

Oral mucosal grafting combined with tenonplasty for ocular surface and lid margin reconstruction in an atypical sectorial chemical burn

A 46-year-old woman presented with chemical injury in both eyes after the instillation of undefined eye-drops prescribed by quack. She had an atypical presentation in the form of bilateral severe necrosis of both lids and whole palpebral conjunctiva. Extensive debridement with conjunctival epitheliectomy, tenonplasty and amniotic membrane transplantation (AMT) was performed. Characteristic differences from typical chemical injuries were a sectorial involvement of ocular surface and keratinisation over distorted lid margins. Lid margin needed replacement by labial mucous membrane for the restoration of ocular surface. Ocular surface reconstruction with AMT in acute phase and mucous membrane grafting for involved lid margins in late phase achieves vision salvage and avoids late complications in drug-induced chemical injury.

http://ift.tt/2xbHSco

Cheyne-Stokes respiration: poor prognostic sign in a patient with heart failure

Description

Patients with congestive heart failure (CHF) have high incidence of sleep-disordered breathing. Two distinct types are known: obstructive sleep apnoea (OSA) and Cheyne-Stokes respiration (CSR).1 Effective heart failure treatment improves CSR but not OSA, indicating that the development of CSR is secondary to heart failure. CSR is characterised by recurrent episodes of central apnoea/hypopnoea interposed with periods of hyperpnoea with waning and waxing pattern of tidal volume. A 5-month-old girl who presented with acute onset of poor appetite and tachypnoea had cardiomegaly on chest X-ray. Echocardiography showed severely depressed left ventricular (LV) function with ejection fraction of 10%. She was diagnosed with LV non-compaction cardiomyopathy and placed on heart transplant list. Her heart failure management included milrinone infusion, diuretics and digoxin. She subsequently worsened with increasing heart rate and tachypnoea. Her telemetry showed evidence of CSR with clinical and echocardiographic evidence of worsening LV function (

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Association between hospital volume and receipt of treatment and survival in patients with glioblastoma

Abstract

The relation between hospital volume and outcomes for patients with glioblastoma is unknown. We undertook this study to determine the effect of hospital volume on treatment received and its effect on survival in patients with glioblastoma. We included patients from the National Cancer Database diagnosed with a glioblastoma from 2006 to 2013. Hospital volume was calculated by examining the treating facilities average number of cases per year and grouping them into tertiles: (low < 9.25, medium 9.26–23.88, and high ≥ 23.39). Treatment was defined as receiving any type of therapeutic surgery, radiation or chemotherapy. Using regression models we examined the relation between hospital volume to treatment received and survival with adjustment for clinical, socioeconomic and institutional factors. The study included 68,726 patients of which 91.8% received treatment. Among patients diagnosed at low volume facilities, 90.1% received treatment versus 94.2% in high volume facilities (p < 0.0001). Compared to low volume centers, the odds ratio of receiving any treatment was 1.01 (CI 95% CI: 0.95–1.09) and 1.43 (95% CI: 1.31–1.55) for medium volume and high volume facilities, respectively. On multivariate analysis for survival among those who received treatment, the hazard of mortality was decreased at high volume (HR 0.92, 95% CI 0.89–0.94) facilities compared to low volume facilities. Patients diagnosed with glioblastoma at a high volume facility (≥23.39 cases per year) have an increased likelihood of receiving treatment. Furthermore, glioblastoma patients may significantly improve their survival by choosing to receive care at a high-volume hospital.

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Involvement of aberrantly expressed microRNAs in the pathogenesis of head and neck squamous cell carcinoma

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that act as fine-tuners of the post-transcriptional control of protein-coding or noncoding RNAs by repressing translation or cleaving RNA transcripts in a sequence-dependent manner in cells. Accumulating evidence have been indicated that aberrantly expressed miRNAs are deeply involved in human pathogenesis, including cancers. Surprisingly, these small, single-stranded RNAs (18–23 nucleotides) have been shown to function as antitumor or oncogenic RNAs in several types of cancer cells. A single miRNA has regulating hundreds or thousands of different mRNAs, and individual mRNA has been regulated by multiple different miRNAs in normal cells. Therefore, tightly controlled RNA networks can be disrupted by dysregulated of miRNAs in cancer cells. Investigation of novel miRNA-mediated RNA networks in cancer cells could provide new insights in the field of cancer research. In this review, we focus on head and neck squamous cell carcinoma (HNSCC) and discuss current findings of the involvement of aberrantly expressed miRNAs in the pathogenesis of HNSCC.

http://ift.tt/2vdOvth

Checkpoint immunotherapy in head and neck cancers

Abstract

Checkpoint inhibitors have recently gained FDA approval for the treatment of cisplatin-resistant recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) by outperforming standard of care chemotherapy and inducing durable responses in a subset of patients. These monoclonal antibodies unleash the patient's own immune system to target cancer cells. HNSCC is a good target for these agents as there is ample evidence of active immunosurveillance in the head and neck and a number of immune evasion mechanisms by which HNSCCs form progressive disease including via the PD-1/PD-L1 axis. As HNSCCs typically possess a moderately high mutation burden, they should express numerous mutation-derived antigen targets for immune detection. However, with response rates less than 20% in clinical trials, there is a need for biomarkers to screen patients as well as clinical trials evaluating novel combinations to improve outcomes. The aim of this review is to provide historical and mechanistic context for the use of checkpoint inhibitors in head and neck cancer and provide a perspective on the role of novel checkpoints, biomarkers, and combination therapies that are evolving in the near term for patients with HNSCC.

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Prognostic factors for disease-free and overall survival of patients with uterine carcinosarcoma

Abstract

Background

Uterine carcinosarcoma (UCS) is a relatively rare and very aggressive tumor. The predictors of survival for patients with UCS have not been determined clearly yet. The aim of the present study was to investigate the possible predictors of disease-free survival (DFS) and overall survival (OS) for patients with UCS.

Methods and materials

All patients with UCS who were treated surgically at a university-based Gynecology Oncology Clinic between January 2008 and December 2014 were recruited into this retrospective cohort study. Data regarding clinical, pathologic and treatment information were obtained retrospectively from hospital records. The Kaplan–Meier method was used to calculate DFS and OS, and Cox regression analysis was performed to define the effects of risk factors on survival.

Results

A total of 88 UCS patients with a median age of 64.5 years were included in the study. Forty-seven (53.4%) patients were diagnosed with stage III disease and seven (7.9%) with stage IV disease. The median follow-up time was 16 months. Among all patients, 60 (68.1%) underwent lymphadenectomy. Optimal cytoreductive surgery was achieved in 67 (76.1%) patients. Stepwise variable selection Cox regression analysis showed that lymph node metastasis was associated with poor DFS (hazard ratio 6.524; 95% CI 2.625–16.211; P < 0.001) and OS (hazard ratio 6.993; 95% CI 2.631–18.587; P < 0.001). Subgroup analysis in both early and advanced-stage diseases revealed no significant impact of risk factors on survival.

Conclusions

Lymph node metastasis is the most significant prognostic factor associated with poor DFS and OS in UCS patients.

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Nedaplatin as a Single-Agent Chemotherapy May Support Palliative Therapy for Patients with Adenoid Cystic Carcinoma: A Case Report

Adenoid cystic carcinoma (ACC) is a rare form of adenocarcinoma, which is a broad term describing any cancer that begins in the glandular tissues. It can be found in the head and neck. We report a patient with recurrent ACC arising from the submandibular gland, treated with 100 mg/m² nedaplatin every 4 weeks. Although our patient's lactate dehydrogenase levels, which is produced by ACC, showed a rising trend throughout the treatment, the level decreased for approximately 2 weeks immediately after administration of nedaplatin every 4 weeks. Thus, there is a possibility that the agent may be effective. Complications such as anorexia and nausea were observed, but they were tolerated and manageable. Nedaplatin may be considered as a supportive agent during palliative therapy for patients with ACC. More clinical trials regarding nedaplatin are necessary, as this study may indicate that a medical approach works well for ACC.
Case Rep Oncol 2017;10:783–789

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What Is Different in the Population of the Brazilian Amazon Region so that They Have a Low Frequency of KRAS Gene Mutations?

Background: Colorectal cancer (CRC) has been described in the medical literature as resulting from many forms of interaction between lifestyle, genetics, and geographical origin. Genetically, the KRAS gene has a negative impact on the general survival and prognosis of patients when mutated. Methods: This study was conducted in Brazil and included information about 60 patients with CRC stage III and IV examined at the Day Hospital Oncológica do Brasil, whose DNA was analyzed with the PCR-DNA method to determine the existence of a KRAS mutation. Results: The results revealed that 18.3% of the individuals analyzed showed a KRAS mutation (24% of mutations were found in men and 14.3% in women), which is a smaller proportion than those found in other large studies across the globe. Conclusion: As our analysis is one of the very first published about this topic, more studies are necessary to understand the role of KRAS mutations and the associated variables in populations such as that of the Amazon region.
Case Rep Oncol 2017;10:777–782

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Why Do Oncologists Hide the Truth? Disclosure of Cancer Diagnoses to Patients in China: A Multisource Assessment using Mixed Methods

Abstract

Background

In the USA and most European countries, cancer diagnoses are disclosed to patients. In China, however, the trend towards full disclosure has progressed slowly. The present study aimed to explore attitudes toward truth-telling practice among physicians, patients, patients' family members, and the general population, and reasons for non-disclosure.

Methods

We administered a short survey to 212 physicians, 143 patients with cancer, 413 family members of patients with cancer, and 1,415 members of the general population. A MANOVA was performed to examine group differences in attitudes toward cancer disclosure. In addition, we interviewed 20 oncologists. Interview data was analyzed using NVivo10. After the interview, we administered another short survey to 143 patients with cancer.

Results

Quantitative data indicated that physicians were the least, and patients the most, in favor of disclosure. Qualitative data among physicians and follow-up surveys among cancer patients revealed five reasons for the concealment of cancer diagnoses by physicians, including lack of awareness of patients' right to knowledge, cultural influences, insufficient medical resources and training, families' financial concerns, and the need to protect doctors from violence.

Conclusion

There is a discrepancy between the needs of patients and those in medical practice. These results deepen our understanding regarding the reasons for oncologists' attitudes towards non-disclosure.

http://ift.tt/2wDFzkf