Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Παρασκευή 8 Ιανουαρίου 2016
Less cost by using hanging maneuver and Pringle maneuver in left lateral hepatectomy through small laparotomy wound—experience of Southern Taiwan
Abstract
Background
Laparoscopic segmentectomy for liver tumor located in the left lateral segment (LLS) is thought to be a standard protocol nowadays with several advantages, such as small wound, few blood loss, and short hospital stay. However, there are still many disadvantages during executing laparoscopic LLS segmentectomy. This manuscript aims to present the technique to execute LLS segmentectomy with small incision, hanging maneuver without Pringle maneuver in patients with tumor at LLS of the liver.
Material and methods
Between November 2010 and July 2011, hepatectomies through small incision for nine patients with benign and malignant tumors were performed at Kaohsiung Chang Gung Memorial Hospital, Taiwan. Perioperative and postoperative results, such as operation time, blood loss, incisional width, and postoperative stay were used to determine consequents for this technique.
Result
Results demonstrated that modified LLS segmentectomy by the author's team was performed successfully in patient with liver tumor with fewer blood loss, smaller incisional width, and lower hospital cost than traditional open surgery. In addition, the instrument cost and blood loss in our series were less than that in laparoscopic LLS segmentectomy in published literature.
Conclusion
Authors concluded that minimally incisional segmentectomy, with less cost and technical demanding, could be an alternative choice in patient with liver tumor at LLS.
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Bilateral salpingectomy can reduce the risk of ovarian cancer in the general population: A meta-analysis
Publication date: March 2016
Source:European Journal of Cancer, Volume 55
Author(s): Sang-Hee Yoon, Soo-Nyung Kim, Seung-Hyuk Shim, Soon-Beum Kang, Sun-Joo Lee
BackgroundThe results of recent studies have suggested that high-grade serous ovarian cancer predominantly arises within the fallopian tubes. The reduction of ovarian cancer (OC) risk in women with a history of bilateral salpingectomy (BS) has been reported. We performed a meta-analysis to determine the impact of BS in preventing OC in the general population.MethodsWe searched the PubMed, MEDLINE, and EMBASE databases and CENTRAL in the Cochrane Library for all English-language articles published up to January 2015, using the key words 'ovarian cancer' and 'bilateral salpingectomy.' Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated by standard meta-analysis techniques.ResultsOf the 77 studies retrieved, three were included in this meta-analysis, including one cohort study and two population-based case-control studies with 3509 patients who underwent BS and 5,655,702 controls who did not undergo salpingectomy. Over the combined study period, 29 of the 3509 BS patients developed OC compared with 44,006 of the 5,655,702 without salpingectomy. The meta-analysis results based on the fixed effects model revealed a significant decrease in the risk of OC occurrence in the patients who underwent BS relative to the controls (OR=0.51, 95% CI 0.35–0.75, I2=0%). This pattern was also observed in subgroup analysis for the study type.ConclusionsOur results suggest that removal of the fallopian tubes is an effective measure to reduce OC risk in the general population. Therefore, prophylactic bilateral salpingectomy should be considered for women who require hysterectomy with benign indications or sterilisation procedures.
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How staging of thin melanoma is changed after the introduction of TNM 7th edition: a population-based analysis
Abstract
Introduction
In 2009, the American Joint Committee on Cancer (AJCC) incorporated the tumor mitotic rate in the melanoma pathological TNM staging system. To investigate the effect of this change on the pT1 substaging of primary cutaneous melanomas, we reclassified the cases collected by a cancer registry according to the 6th and the 7th editions of AJCC melanoma staging.
Methods
Patients with pathological T1 melanoma diagnosed in the period 2000–2008 were selected from Tuscan Cancer Registry. The histological reports were reviewed and pT1 melanomas classified according to both the 6th and the 7th editions of the AJCC staging system. The shift of melanomas between pT1 substages was analyzed.
Results
Among the 242 pT1 melanomas collected in the study period and with mitotic index available, there were 202 (83 % of all pT1) and 175 (72 %) pT1a, according to the 6th and the 7th editions of the AJCC melanoma staging, respectively. When the 7th edition was used, 20 % of all pT1a melanomas shifted to pT1b, and 32 % of all pT1b melanomas shifted to pT1a. A poor level agreement between the two TNM staging systems, measured by the Cohen's kappa coefficient, was found (K = 0.37).
Conclusions
The addition of mitotic activity to the pathological staging resulted in an increase in pT1b proportion and in a change in the classification of some cases. This modification could influence the clinical approach, with a different use of the sentinel lymph node biopsy, and underlines the role of mitosis evaluation in the management of thin melanoma patients.
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Comparison of nine prognostic scores in patients with brain metastases of breast cancer receiving radiotherapy of the brain
Abstract
Purpose
Several prognostic indices (PI) have been developed to stratify patients with brain metastases in groups with good or bad prognosis. The aim of our study was to compare nine prognostic scores for patients with brain metastases (BM) of breast cancer receiving radiotherapy.
Methods
The clinical data of 139 breast cancer patients with BM were collected retrospectively. All patients were treated with cerebral radiotherapy or surgery followed by radiotherapy between January 2007 and December 2012. The prognostic value and accuracy of recursive partitioning analysis (RPA), RPA II, graded prognostic assessment (GPA), basic score for BM, Breast-RPA, Breast-GPA, Rades Score 2011, Germany Score and Breast Rades Score were assessed.
Results
The median survival after BM diagnosis in our cohort was 14 months. The overall 6-month, 1-, 2- and 3-year survival rates were 49.6, 37.4, 20.9 and 13.7 %, respectively. Most of the PI were associated with OS, but univariate analysis favored GPA regarding OS. GPA was the most accurate score to identify patients with long (longer than 12 months) and Breast-GPA patients with short (<3 months) life expectancy.
Conclusions
GPA and Breast-GPA seem to be the most useful scores and perform better than other PI for breast cancer patients with BM receiving radiotherapy.
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Risk factors for outcome in refractory acute myeloid leukemia patients treated with a combination of fludarabine, cytarabine, and amsacrine followed by a reduced-intensity conditioning and allogeneic stem cell transplantation
Abstract
Introduction
Hematopoietic stem cell transplantation (HCT) is considered a standard treatment for high-risk acute myeloid leukemia (AML) in first or second complete remission (CR). Unfortunately, not all patients achieve complete remission prior to HCT. We sought to establish predictive factors for survival after HCT for refractory AML after FLAMSA-RIC.
Patients and methods
We analyzed the outcome of 44 consecutive patients aged between 21 and 65 years transplanted at the University Hospitals of Jena and Leipzig for refractory AML between 2006 and January 2013. Conditioning for HCT was performed with chemotherapy consisting of fludarabine, cytarabine, and amsacrine followed by total body irradiation or busulfan combined with cyclophosphamide. Antithymocyte globulin was given when transplanting from unrelated donors (FLAMSA-RIC).
Results
Estimated overall survival (OS) and event-free survival (EFS) at 3 years after a median follow-up of 34 (range 6–71) months were 15 and 12 %, respectively. Causes of death were relapse in 66 %, infection in 11 %, and graft-versus-host disease (GvHD) in 7 % of all patients. Twenty-five from 42 evaluable patients (60 %) achieved CR 4 weeks after HCT, while eight patients had partial remission (PR), and nine patients had stable disease (SD). Another six patients with PR and SD achieved CR (overall CR rate 74 %) from 4 weeks to day 90 after HCT following reduction in immunosuppression. The strongest favorable factors in univariate analysis for OS, EFS, and RI were ≥98 % total donor chimerism 2–4 weeks after HCT and <3 lines of pretreatment prior to HCT. In addition, better OS was detected in patients with <20 % bone marrow blasts alone (32 vs. 5 % at 3 years) and in combination with <3 lines of pretreatment (38 vs. 4 % at 3 years). Only a trend for better EFS and lower RI was observed in patients with limited chronic GvHD. In addition, a lower RI was seen in patients with <5 % blasts 4 weeks after HCT. Multivariate analysis revealed that ≥98 % donor chimerism 2–4 weeks after HCT for OS, EFS, and RI and <3 lines of pretreatment for OS and EFS are the strongest predictors for better outcome.
Conclusion
FLAMSA-RIC shows long-term survival in refractory AML patients. Factors for favorable outcome are <20 % bone marrow blasts prior to HCT, <3 lines of pretreatment and complete donor chimerism after HCT.
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Drastic morphological and molecular differences between lymph node micrometastatic tumors and macrometastatic tumors of lung adenocarcinoma
Abstract
Purpose
The expansion of micrometastatic tumors to macrometastatic ones is thought to be tightly regulated by several microenvironmental factors. The aim of this study was to elucidate the morphological and phenotypical differences between micrometastatic and macrometastatic tumors.
Method
We first examined the morphological characteristics of 66 lymph node (LN) micrometastatic tumors (less than 2 mm in size) and 51 macrometastatic tumors (more than 10 mm in size) in 42 lung adenocarcinoma cases. Then, we evaluated the expression level of E-cadherin, S100A4, ALDH1, and Geminin in cancer cells and the number of smooth muscle actin (SMA), CD34, and CD204 (+) stromal cells in the primary tumors, matched micrometastatic tumors, and macrometastatic tumors (n = 34, each).
Results
Tumor budding reflects the process of EMT, and stromal reactions were observed more frequently in macrometastatic tumors (P < 0.001). E-cadherin staining score for the micrometastatic tumors was significantly higher than that for the primary tumors (P < 0.001). In contrast, the E-cadherin staining score for the macrometastatic tumors was significantly lower than that for the micrometastatic tumors (P = 0.017). As for the stromal cells, the numbers of SMA (+) fibroblasts, CD34 (+) microvessels, and CD204 (+) macrophages were significantly higher for the macrometastatic tumors and primary tumors than for the micrometastatic tumors (P < 0.001, all).
Conclusion
The present study clearly showed that dynamic microenvironmental changes (e.g., EMT-related changes in cancer cells and structural changes in stromal cells) occur during the growth of micrometastases into macrometastases.
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Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population
Abstract
Purpose
The C → T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk.
Methods
We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC.
Results
No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50–0.96, dominant model).
Conclusion
The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.
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Long-term follow-up of the AML97 study for patients aged 60 years and above with acute myeloid leukaemia: a study of the East German Haematology and Oncology Study Group (OSHO)
Abstract
Introduction
Treatment of patients (pts) with acute myelogenous leukaemia (AML) above 60 years remains a challenge. We report long-term follow-up of the AML97 study, where pts were registered at diagnosis and received treatment dependent on their comorbidities: dose-intense cytarabine (AraC) and anthracycline in the curative arm, and low-dose chemotherapy in the palliative arm or best supportive care.
Materials and Methods
A total of 618 pts were enrolled in this protocol (curative 471, palliative 115 and supportive 32). In the curative arm, complete remission (CR) was obtained in 66.8 % of pts and the estimated probability of being alive at 2 years was 0.30 (±0.02 SE). In multivariate analysis, gender (p = 0.005), performance status (p = 0.04) and cytogenetics (p = 0.002) were significant factors for CR. With a median follow-up of 10 (range 0.1–11.8) years, the estimated probability of being event-free after 2 and 5 years according to cytogenetics was 0.48 ± 0.11 and 0.48 ± 0.11 for favourable, 0.20 ± 0.03 and 0.09 ± 0.03 for normal, 0.18 ± 0.06 and 0.10 ± 0.05 for other standard risk and 0.10 ± 0.03 and 0.05 ± 0.02 for unfavourable karyotypes, respectively. The median survival time for pts treated with palliative chemotherapy was 54 and 11 days with best supportive care only.
Conclusion
In conclusion, treatment of older AML pts with dose-intense AraC is feasible in the majority of pts and induces high rates of CR. Nevertheless, except for favourable karyotype, OS and event-free survival remain low. These results need to be viewed in relation to the new modalities including stem cell transplantation following non-myeloablative conditioning, epigenetic and molecular therapies.
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Octreotide and Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors
Abstract
Neuroendocrine tumors are heterogeneous, rare malignancies that arise most commonly in the gastrointestinal tract and pancreas. They often secrete vasoactive substances resulting in carcinoid syndrome and the tumor cells exclusively express somatostatin receptors. Octreotide and lanreotide are the two synthetic somatostatin analogs used for the control of carcinoid symptoms and tumor progression in advanced inoperable disease. Recent pivotal trials (PROMID and CLARINET studies) established their antitumor activity. We discuss the available data to support their use as symptom controlling and antiproliferative agents. This article also reviews the guidelines (National Comprehensive Cancer Network and North American Neuro Endocrine Tumor Society), cost-analysis (suggesting the cost-effectiveness of lanreotide autogel compared to higher doses of octreotide long acting release formulation in refractory patients), and future directions of somatostatin analogs in the management of patients refractory to conventional doses of octreotide and lanreotide.
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Quality-of-life and performance status results from the phase 3 RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma
The RAINBOW phase 3 trial showed that addition of ramucirumab to paclitaxel yielded survival benefits for previously treated patients with advanced gastric or gastroesophageal junction adenocarcinoma. Now analyses reveal that ramucirumab also maintains patient-reported quality of life, lengthening the time to deterioration of patient symptoms and functions, and slowing performance status decline.
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Management of Immune Checkpoint Blockade Dysimmune Toxicities: a collaborative position paper
Based on Gustave Roussy immunotherapy clinical practice and experience in irAEs management together with our network of organs' specialists, we propose here some practical guidelines for the oncologist to help in the clinical care of patients under immune checkpoint blockade therapy.
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Pre-operative versus post-operative docetaxel-cisplatin-fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial
This is a SAKK/IEO prospective randomized phase III trial comparing docetaxel/cisplatin/fluorouracil (TCF) regimen preoperatively versus postoperatively in locally advanced resectable gastric cancer (RGC). Compared with MAGIC (Cunningham, NEJM 2006) and FFCD (Ychou, JCO 2011) trials, which were perioperative positive trials in resectable gastric cancer, ours was based on a more rigid baseline staging, including CT-scan, EUS, bone scan and laparoscopy. Furthermore it did not include esophageal cancers, as in the MAGIC, and it included for the vast majority distal gastric cancer, unlike the FFCD trial, which enrolled mainly junction cancers. The SAKK/IEO trial was conducted between December 1999 and August 2005 and it was early stopped at 70 patients due to slow accrual, as the EORTC trial in the same setting (Schuhmacher et al., JCO 2010). With a 10 year follow-up no statistically significant difference was observed for the primary endpoint, event free survival (EFS), even though it should be considered that the early interruption made the study underpowered. Interestingly EFS was higher than expected in both arms, with 2.5 years in arm A and B compared to the expected 1.98 vs. 1.29 years, respectively. Also the 5-y OS was high in both arms, overlapping to that of some Western adjuvant trials and better than that of other neoadjuvant chemotherapy trials in RGC, including MAGIC, FFCD and EORTC. Finally, TCF resulted better feasible before than after surgery, D2 resection was safe after TCF and pathological complete responses were promising.
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Pathways to improving combined modality therapy for stage III non-small cell lung cancer
Recent progress in the fields of molecular biology and immunology has improved survival for patients with advanced disease. There have also been improvements in radiotherapy including more precise targeting, modified fractionation and the use of newer beams. It is hoped that these tools can be successfully employed to better care for patients with stage III disease.
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Interpreting febrile neutropenia rates from randomized controlled trials for consideration of primary prophylaxis in the real world: A systematic review and meta-analysis
Guidelines recommend primary prophylaxis (PP) with granulocyte colony-stimulating factors (G-CSF) for patients above a febrile neutropenia (FN) risk threshold of 20%. FN rates in randomized controlled trials (RCT) are greater than observational studies in many breast cancer chemotherapy regimens. A 13% (95% CI: 8.7%-17.9%) FN rate in RCT would translate into 20% FN rate in observational study.
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Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy
Anti-PD-1 therapy has demonstrated significant activity in metastatic melanoma. We report good local control and minimal neurotoxicity with the combination of nivolumab and stereotactic radiation in the management of melanoma brain metastases. Overall survival and distant brain metastases control appear improved.
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Changes in Tumor Expression of HER2 and Hormone Receptors Status after Neoadjuvant Chemotherapy in 21,755 Patients from the Japanese Breast Cancer Registry
We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.
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Synthetic Bax-Anti Bcl 2 combination module actuated by super artificial hTERT promoter selectively inhibits malignant phenotypes of bladder cancer
Abstract
Background
The synthetic biology technology which enhances the specificity and efficacy of treatment is a novel try in biomedical therapy during recent years. A high frequency of somatic mutations was shown in the human telomerase reverse transcriptase (hTERT) promoter in bladder cancer, indicating that a mutational hTERT promoter might be a tumor-specific element for bladder cancer therapy. In our study, we aimed to construct a synthetic combination module driven by a super artificial hTERT promoter and to investigate its influence on the malignant phenotypes of bladder cancer.
Methods
The dual luciferase assay system was used to verify the driven efficiency and tumor-specificity of the artificial hTERT promoter and to confirm the relationship between ETS-1 and the driven efficiency of the artificial hTERT promoter. CCK-8 assay and MTT assay were used to test the effects of the Bax-Anti Bcl2 combination module driven by the artificial hTERT promoter on cell proliferation. Simultaneously, the cell apoptosis was detected by the caspase 3ELISA assay and the flow cytometry analysis after transfection. The results of CCK-8 assay and MTT assay were analyzed by ANOVA. The independent samples t-test was used to analyze other data.
Results
We demonstrated that the artificial hTERT promoter had a higher driven efficiency which might be regulated by transcription factor ETS-1 in bladder cancer cells, compared with wild-type hTERT promoter. Meanwhile, the artificial hTERT promoter showed a strong tumor-specific effect. The cell proliferation inhibition and apoptosis induction were observed in artificial hTERT promoter- Bax-Anti Bcl2 combination module -transfected bladder cancer 5637 and T24 cells, but not in the module -transfected normal human fibroblasts.
Conclusion
This module offers us a useful synthetic biology platform to inhibit the malignant phenotypes of bladder cancer in a more specific and effective way.
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The Effect of Caffeic Acid Phenethyl Ester (CAPE) Fortification on the Liver Element Distribution that Occurs After Exercise
Abstract
The purpose of this study is to examine the effect of the caffeic acid phenethyl ester (CAPE) fortification applied to the rats, which were made to exercise, on the liver elements. The study was conducted on 32 Sprague-Dawley male rats. The experimental animals were divided into 4 groups in equal numbers. Group 1 is the group which was applied 10 μmol/kg/day CAPE as intraperitoneal (IP) for 4 weeks, and they were not made to exercise at the end of the application. Group 2 is the group which was applied 10 μmol/kg/day CAPE as IP for 4 weeks, and they were made to exercise at the end of the 4th week. Group 3 is the general control group. Group 4 is the swimming control group. A 10 mmol/kg CAPE application dissolved in ethyl alcohol of 10 % was applied to the CAPE group. Sodium (Na), zinc (Zn), calcium (Ca), iron (Fe), chrome (Cr), magnesium (Mg), potassium (K), copper (Cu) and cadmium (Cd) levels were identified in the liver samples at the end of the application. The results of the study suggest that exercise and CAPE fortification in rats cause changes in the Na, Zn, Ca, Fe and Cr parameters in liver tissues, and it does not affect Cd, Cu, Mg and K element distribution. It is thought that CAPE fortification would be helpful for preserving those parameters whose levels are known to be changing with exercise.
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MeHg Suppressed Neuronal Potency of Hippocampal NSCs Contributing to the Puberal Spatial Memory Deficits
Abstract
Hippocampal neurogenesis-related structural damage, particularly that leading to defective adult cognitive function, is considered an important risk factor for neurodegenerative and psychiatric diseases. Normal differentiation of neurons and glial cells during development is crucial in neurogenesis, which is particularly sensitive to the environmental toxicant methylmercury (MeHg). However, the exact effects of MeHg on hippocampal neural stem cell (hNSC) differentiation during puberty remain unknown. This study investigates whether MeHg exposure induces changes in hippocampal neurogenesis and whether these changes underlie cognitive defects in puberty. A rat model of methylmercury chloride (MeHgCl) exposure (0.4 mg/kg/day, PND 5–PND 33, 28 days) was established, and the Morris water maze was used to assess cognitive function. Primary hNSCs from hippocampal tissues of E16-day Sprague–Dawley rats were purified, identified, and cloned. hNSC proliferation and differentiation and the growth and morphology of newly generated neurons were observed by MTT and immunofluorescence assays. MeHg exposure induced defects in spatial learning and memory accompanied by a decrease in number of doublecortin (DCX)-positive cells in the dentate gyrus (DG). DCX is a surrogate marker for newly generated neurons. Proliferation and differentiation of hNSCs significantly decreased in the MeHg-treated groups. MeHg attenuated microtubule-associated protein-2 (MAP-2) expression in neurons and enhanced the glial fibrillary acidic protein (GFAP)-positive cell differentiation of hNSCs, thereby inducing degenerative changes in a dose-dependent manner. Moreover, MeHg induced deficits in hippocampus-dependent spatial learning and memory during adolescence as a consequence of decreased generation of DG neurons. Our findings suggested that MeHg exposure could be a potential risk factor for psychiatric and neurodegenerative diseases.
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Critical Thresholds of Antioxidant and Immune Function Parameters for Se deficiency Prediction in Dairy Cows
Abstract
The aim of this study was to determine the plasma selenium (Se) levels of lactating cows and to evaluate its association with antioxidant ability and immune function. In a descriptive study, 20 healthy Holstein cows with normal Se level (C) and 30 Holstein cows with subclinical Se deficiency (T) were randomly selected between 14 and 21 days postpartum from a dairy farm, according to a cutoff point of 70 mg/L Se in plasma. Analysis of biochemical parameters of antioxidant and immune function were performed on all the cows, and the risk prediction thresholds for subclinical Se deficiency were determined by area under receiver operating characteristic curve. Cows in the T group had significantly lower plasma Se concentrations compared with cows in the C group (52.16 ± 8.81 vs. 80.37 ± 8.46 μg/L, P = 0.02). There was a marked decrease in plasma glutathione peroxidase (GSH-Px) activity in the T group that correlated positively with the plasma Se level (R = 0.65, P = 0.00), and a significant increase of plasma methane dicarboxylic aldehyde (MDA), total nitric oxide synthase, and lipid peroxidation that correlated negatively with plasma Se levels (R = −0.47, P = 0.01; R = −0.33, P = 0.04; R = −0.40, P = 0.03). Furthermore, there were significantly lower plasma tumor necrosis factor-α and immunoglobulin G levels in the T group that correlated positively with plasma Se levels (R = 0.41, P = 0.01 and R = 0.45, P = 0.01), and a markedly lower plasma interleukin-6 level that correlated negatively with plasma Se levels (R = −0.38, P = 0.02). In addition, if plasma GSH-Px activity was less than 42.37 U/ml, the risk of Se deficiency was significantly increased in lactating cows. These results suggest that low plasma Se levels may reduce the antioxidant ability and immune function, and the risk of low plasma Se level may be predicted effectively by plasma GSH-Px activity in lactating cows.
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Inhibition of miR-15b decreases cell migration and metastasis in colorectal cancer
Abstract
Colorectal cancer (CRC) has a high prevalence and mortality rate. Biomarkers for predicting the recurrence of CRC are not clinically available. This study investigated the role of circulating miR-15b in the prediction of CRC recurrence and the associated mechanism. miR-15b levels in plasma and tissues were measured by real-time PCR. Metastasis suppressor-1 (MTSS1) and Klotho protein expression were detected by Western blot and immunohistochemistry. Invasion and migration of CRC tumor cells were measured by transwell plates. Liver metastasis was established by intraspleen injection of HCT116 cells. Plasma miR-15b levels were significantly higher in CRC patients than in healthy controls, in CRC patients with metastasis than in CRC patients without metastasis, and in CRC patients with recurrence than in CRC patients without recurrence in the 5-year follow-up. miR-15b level in CRC tumors was significantly higher than that in peritumoral tissues. High plasma miR-15b level and negative MTSS1 and Klotho expression in tumor tissues significantly correlated with poor survival. Inhibition of miR-15b activity by adenovirus carrying antimiR-15b sequence significantly increased MTSS1 and Klotho protein expression and subsequently decreased colony formation ability, invasion, and migration of HCT116 cells in vitro and liver metastasis of HCT116 tumors in vivo. In conclusion, high abundance of circulating miR-15b correlated with tumor metastasis, recurrence, and poor patient prognosis through downregulation of MTSS1 and Klotho protein expression.
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Correlations of fascin-1 and cadherin-17 protein expression with clinicopathologic features and prognosis of patients with gastric cancer
Abstract
We aim to explore the associations of fascin-1 and cadherin-17 in gastric cancer (GC) to the clinicopathologic features and prognosis of GC. Case group included 204 GC tissues while control group comprised 204 paired adjacent cancer tissues. Expressions of fascin-1 and cadherin-17 were measured with immunohistochemistry and western blot and then analyzed statistically in relation to clinicopathologic features and survival time. Survival curve was drawn by Kaplan-Meier method, and independent prognostic factors were identified with Cox proportional hazards regression model. Fascin-1 was positively expressed in 45.1 % of GC tissues and in 27.5 % of adjacent cancer tissues, respectively (P < 0.05); cadherin-17 was positively expressed in 51.5 % of GC tissues and in 33.8 % of adjacent cancer tissues (P < 0.05). Fascin-1 expression in GC tissues was related to tumor size (P = 0.001) and Lauren classification (P = 0.001). Cadherin-17 expression in GC tissues was related to tumor size (P < 0.001), Lauren classification (P = 0.009), clinical staging (P = 0.001), and distant metastasis (P = 0.002). Fascin-1 expression was positively correlated with cadherin-17 expression in GC tissues (r = 0.828, P < 0.01). Patients with positive expression of both fascin-1 and cadherin-17 had lower survival rates than those with negative expression (all P < 0.01). Cox regression analysis showed that fascin-1 expression, cadherin-17 expression, tumor size, and differentiation were independent risk factors for GC (all P < 0.05). Fascin-1 and cadherin-17 are related to clinicopathologic features of GC and are independent adverse prognostic factors for GC.
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Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer
Abstract
Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070–7.933), distant metastasis (HR = 3.860, 95 % CI 1.507–9.884), and cancer death (HR = 7.252, 95 % 2.189–24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185–4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300–19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.
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Successful ethinylestradiol therapy for a metastatic breast cancer patient with heavily pre-treated with endocrine therapies
Abstract
The critical strategy leading to the success of endocrine therapy in metastatic breast cancer is ex tended duration of treatment. Here, we report a case with late-stage metastatic breast cancer who dramatically responded to high-dose estrogen treatment with a long-term stable disease. A 52-year-old female with metastatic breast cancer was referred to our hospital. She had already received several courses of systemic therapy: LH-RH agonist and tamoxifen and docetaxel. At first visit to us, she had a multiple liver tumor and an irregular mass in the left breast. We started endocrine therapy of LH-RH agonist and anastrozole with a stable disease for 12 months. After the disease progression, LH-RH agonist and letrozole, TS-1, vinorelubine, and nab-paclitaxel were administered. Further, she received the exemestane therapy as the fifth line, but the disease progressed after 4 months. We then started ethinylestradiol (EE2) therapy. Two months later, the tumor in liver rapidly decreased from 15.8 to 10.6 cm, of which the tumor shrinkage rate was 33 %. Subsequently, the patient had stable disease for 12 months. After 14-month EE2 therapy, the patient had a regrowth of the liver tumors, and was then treated with letrozole again. This therapy had continued for 5 months. Estrogen therapy is beneficial for postmenopausal patients with heavily pre-treated who could have acquired resistance to aromatase inhibitor.
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Value of diffusion-weighted imaging combined with conventional magnetic resonance imaging in the diagnosis of thecomas/fibrothecomas and their differential diagnosis with malignant pelvic solid tumors
Abstract
Background
Our study aims to determine the value of diffusion-weighted imaging (DWI) combined with conventional magnetic resonance imaging (MRI) in the diagnosis of thecomas/fibrothecomas and their differential diagnosis with malignant pelvic solid tumors.
Methods
In total, 36 thecomas/fibrothecomas and 40 malignant pelvic solid tumors were included in our study. All patients underwent 1.5 T conventional MRI and DWI examinations except one patient with a fibrothecoma in whom DWI examination was not performed. The clinical features and characteristics of conventional MRI and DWI of these two groups were analyzed. Apparent diffusion coefficient (ADC) values were measured and compared between groups. Univariate analysis, multivariate logistic regression analysis, and the receiver operating characteristic curve were used for statistical analysis.
Results
All the thecomas/fibrothecomas showed isointensity on T1 weighted imaging (T1WI) and 77.8 % (28/36) lesions showed hypo- to isointensity on T2 weighted imaging (T2WI). After administration of contrast medium, 94.4 % (34/36) tumors appeared as minor to mild enhancement. On DWI, they showed a diversity of low to very high signal intensity. All malignant pelvic masses manifested as hyperintensity on T2WI and 87.5 % (35/40) tumors showed very high signal (grade 3) on DWI. Higher area under the curve (AUC) and specificity could be achieved by using the lowest ADC value than the mean ADC value. Multivariate logistic regression analysis showed that shape, signal intensity on T2WI, capsule, and the lowest ADC value were the important indicators in discriminating thecomas/fibrothecomas from malignant pelvic solid tumors.
Conclusions
The combination of DWI and conventional MRI is of great value in the diagnosis of thecomas/fibrothecomas and their differential diagnosis with malignant pelvic solid tumors.
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Tumour-induced osteomalacia: a literature review and a case report
Abstract
Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterised by severe hypophosphataemia and osteomalacia, with renal phosphate wasting that occurs in association with tumour. The epidemiology likewise aetiology is not known. The clinical presentation of TIO includes bone fractures, bone and muscular pains, and sometimes height and weight loss. TIO may be associated with mesenchymal tumours which may be benign or malignant in rare cases. Mesenchymal tumour itself may be related to fibroblast growth factor 23 (FGF23), which is responsible for hypophosphataemia and phosphaturia occurring in this paraneoplastic syndrome. Hypophosphataemia, phosphaturia and elevated alkaline phosphatase are the main laboratory readings that may lead to more precise investigations and better diagnosis. Finding the tumour can be a major diagnostic challenge and may involve total body magnetic resonance imaging, computed tomography and scintigraphy using radiolabelled somatostatin analogue. The treatment of choice for TIO is resection of a tumour with a wide margin to insure complete tumour removal, as recurrences of these tumours have been reported. We provide here an overview on the current available TIO case reports and review the best practices that may lead to earlier recognition of TIO and the subsequent treatment thereof, even though biochemical background and the long-term prognosis of the disease are not well understood. This review also includes a 4-year-long history of a patient that featured muscular pains, weakness and multiple stress fractures localised in the hips and vertebra with subsequent recovery after tumour resection. Because the occurrence of such a condition is rare, it may take years to correctly diagnose the disease, as is reported in this case report.
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Impact of Robotic Platforms on Surgical Approach and Costs in the Management of Morbidly Obese Patients with Newly Diagnosed Uterine Cancer
Abstract
Background
Minimally invasive surgery (MIS) is associated with decreased complication rates, length of hospital stay, and cost compared with laparotomy. Robotic-assisted surgery—a method of laparoscopy—addresses many of the limitations of standard laparoscopic instrumentation, thus leading to increased rates of MIS. We sought to assess the impact of robotics on the rates and costs of surgical approaches in morbidly obese patients with uterine cancer.
Methods
Patients who underwent primary surgery at our institution for uterine cancer from 1993 to 2012 with a BMI ≥40 mg/m2 were identified. Surgical approaches were categorized as laparotomy (planned or converted), laparoscopic, robotic, or vaginal. We identified two time periods based on the evolving use of MIS at our institution: laparoscopic (1993–2007) and robotic (2008–2012). Direct costs were analyzed for cases performed from 2009 to 2012.
Results
We identified 426 eligible cases; 299 performed via laparotomy, 125 via MIS, and 2 via a vaginal approach. The rates of MIS for the laparoscopic and robotic time periods were 6 % and 57 %, respectively. The rate of MIS was 78 % in this morbidly obese cohort in 2012; 69 % were completed robotically. The median length of hospital stay was 5 days (range 2–37) for laparotomy cases and 1 day (range 0–7) for MIS cases (P < 0.001). The complication rate was 36 and 15 %, respectively (P < 0.001). The rate of wound-related complications was 27 and 6 %, respectively (P < 0.001). Laparotomy was associated with the highest cost.
Conclusions
The robotic platform provides significant health and cost benefits by increasing MIS rates in this patient population.
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Oncologic Risk Stratification Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendiceal Carcinomatosis
Abstract
Introduction
Patients with peritoneal carcinomatosis (PC) of appendiceal origin demonstrate variable oncologic outcomes, despite aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS–HIPEC). We sought to devise a prognostic risk stratification system for oncologic outcomes following CRS–HIPEC.
Methods
A total of 197 patients undergoing CRS–HIPEC for the treatment of appendiceal PC were reviewed from a prospective database. Kaplan–Meier survival curves and multivariate Cox regression models were used to identify prognostic factors affecting oncologic outcomes. Clinicopathologic variables affecting overall survival (OS) were utilized to develop a prognostic staging system and nomograms.
Results
Univariate and multivariate Cox regression analysis indicated that high-grade tumor histology, lymph node metastasis, and incomplete cytoreduction were high-risk features, adversely affecting OS. Patients were stratified on the presence of high-risk features as follows: low-risk patients had no risk factors (n = 102); intermediate-risk patients had one risk factor (n = 49); and high-risk patients had more than one risk factor (n = 46). Median OS for low-risk patients was not reached, and was 43 and 22 months for intermediate-risk and high-risk patients, respectively. Five-year OS was 72, 43, and 13 % for low-, intermediate- and high-risk patients, respectively (p < 0.0003 for low vs. intermediate risk, and p = 0.06 for intermediate vs. high risk).
Conclusions
We propose a three-tier staging system for appendiceal PC following CRS–HIPEC, based on histologic grade, lymph node involvement, and completeness of cytoreduction. The presence of any one or more of these high-risk features significantly decreased survival in our single-institution database and provided the basis for a prognostic staging system and corresponding nomograms.
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Melanoma Patient-Reported Quality of Life Outcomes Following Sentinel Lymph Node Biopsy, Completion Lymphadenectomy, and Adjuvant Interferon: Results from the Sunbelt Melanoma Trial
Abstract
Background
Quality of life (QOL) and physical condition (PC) outcomes after sentinel lymph node biopsy (SLNB), completion lymph node dissection (CLND), and adjuvant therapy with interferon alfa-2b (IFN) were evaluated in this study.
Methods
Self-reported QOL and PC scores were evaluated in patients enrolled in a prospective, multicenter, randomized, clinical trial evaluating adjuvant IFN. After SLN biopsy, patients with a positive SLN underwent CLND then were randomized to adjuvant IFN or observation. QOL and PC scores were compared between patients who underwent SLNB alone, CLND without IFN, and CLND with IFN. Time to return to baseline QOL and PC scores reported at the time of SLNB was recorded and compared.
Results
There were statistically significant differences in time to return to baseline QOL (p = 0.0018) and PC (p = 0.0018) scores across the three treatment groups. The time to return to baseline QOL and PC scores was similar for SLND and CLND alone. Differences in time to return to baseline QOL and PC were sustained when stratified by recurrence status but did not differ significantly for different lymph node regions. There was a delay in return to baseline QOL and PC condition scores that was sustained beyond the cessation of IFN therapy.
Conclusions
CLND is well-tolerated with a similar effect on self-reported QOL outcomes in both the short- and long-term compared with SLNB alone. IFN therapy is associated with worse QOL outcomes compared with SLNB and CLND, an effect that may be sustained following cessation of adjuvant IFN.
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