Publication date: Available online 16 November 2016
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Tommaso Colangelo, Giovanna Polcaro, Livio Muccillo, Giovanna D'Agostino, Valeria Rosato, Pamela Ziccardi, Angelo Lupo, Gianluigi Mazzoccoli, Lina Sabatino, Vittorio Colantuoni
The network of bidirectional homotypic and heterotypic interactions established among parenchymal tumour cells and surrounding mesenchymal stromal cells generates the tumour microenvironment (TME). These intricate crosstalks elicit both beneficial and adverse effects on tumour initiation and progression unbalancing the signals and responses from the neighbouring cells.Here, we highlight the structure, activities and evolution of TME cells considering a novel colorectal cancer (CRC) classification based on differential stromal composition and gene expression profiles. In this scenario, we scrutinise the molecular pathways that either change or become corrupted during CRC development and their relative prognostic value.Finally, we survey the therapeutic molecules directed against TME components currently available in clinical trials as well as those with stronger potential in preclinical studies. Elucidation of dynamic variations in the CRC TME cell composition and their relative contribution could provide novel diagnostic or prognostic biomarkers and allow more personalised therapeutic strategies.
http://ift.tt/2f2z12f
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 16 Νοεμβρίου 2016
Friend or foe?
Connected Health: An Important Tool for Making Progress against Cancer
In the year 2000, when I was director of NCI's Division of Cancer Control and Population Sciences, only about half of U.S. adults had Internet access. The first iPhone was still 7 years in the future. Few health systems used electronic health records (EHRs) for patient care, and the notion of patients communicating with their health providers and accessing their health records via their own computers was science fiction for most people.
There were—and still are, to a lesser extent—large disparities by age and race in access to and use of the Internet, and at NCI, we were already focused on overcoming this "digital divide." WiFi was not ubiquitous, and I remember many offsite meetings where we had to go outside to get a wireless signal.
http://ift.tt/2fZ4O8X
Connected Health: An Important Tool for Making Progress against Cancer
In the year 2000, when I was director of NCI's Division of Cancer Control and Population Sciences, only about half of U.S. adults had Internet access. The first iPhone was still 7 years in the future. Few health systems used electronic health records (EHRs) for patient care, and the notion of patients communicating with their health providers and accessing their health records via their own computers was science fiction for most people.
There were—and still are, to a lesser extent—large disparities by age and race in access to and use of the Internet, and at NCI, we were already focused on overcoming this "digital divide." WiFi was not ubiquitous, and I remember many offsite meetings where we had to go outside to get a wireless signal.
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Understanding the impact of pelvic organ motion on dose delivered to target volumes during IMRT for cervical cancer
Advanced radiotherapy techniques reduce normal tissue dose by conforming closely to target volumes. In cervical cancer radiotherapy, organ filling affects clinical target volume (CTV; cervix, uterus) position. This study estimates the dosimetric effect of this primary CTV position variation during chemoradiation.
http://ift.tt/2fYYrSW
Central liver toxicity after SBRT: An expanded analysis and predictive nomogram
To further explore the correlation of central biliary tract (cHBT) radiation doses with hepatobiliary toxicity (HBT) after stereotactic body radiation therapy (SBRT) in a larger patient dataset.
http://ift.tt/2fH3PHn
Patterns of care and survival outcomes in patients with pineal parenchymal tumor of intermediate differentiation: An individual patient data analysis
Pineal parenchymal tumor constitutes less than 1% of all CNS tumors. Pineal parenchymal tumor of intermediate differentiation is a rare tumor arising from the pineal parenchyma lying between the spectrum of Pineocytoma and Pineoblastoma.
http://ift.tt/2fYRQIe
Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma
A constant relative biological effectiveness (RBE) is used for clinical proton therapy; however, experimental evidence indicates that RBE can vary. We analyzed pediatric ependymoma patients who received proton therapy to determine if areas of normal tissue damage indicated by post-treatment image changes were associated with increased biological dose effectiveness.
http://ift.tt/2fH4FUP
Fentanyl pectin nasal spray for painful mucositis in head and neck cancers during intensity-modulated radiation therapy with or without chemotherapy
Abstract
Purpose
The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent.
Methods
A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT.
Results
Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use.
Conclusions
FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use.
http://ift.tt/2f62rQv
A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM)
Abstract
Purpose
To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology.
Methods
A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement.
Results
Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12–24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival.
Conclusions
High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.
http://ift.tt/2fXAsjl
Fentanyl pectin nasal spray for painful mucositis in head and neck cancers during intensity-modulated radiation therapy with or without chemotherapy
Abstract
Purpose
The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent.
Methods
A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT.
Results
Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use.
Conclusions
FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use.
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A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM)
Abstract
Purpose
To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology.
Methods
A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement.
Results
Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12–24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival.
Conclusions
High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.
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Programmed Cell Death-Ligand 1 (PD-L1) Expression in Anal Cancer.
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Disparity in Outcomes for Adolescent and Young Adult Patients Diagnosed With Pediatric Solid Tumors Across 4 Decades.
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A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer.
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Programmed Cell Death-Ligand 1 (PD-L1) Expression in Anal Cancer.
http://ift.tt/2f228mf
Disparity in Outcomes for Adolescent and Young Adult Patients Diagnosed With Pediatric Solid Tumors Across 4 Decades.
http://ift.tt/2giZIG5
A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer.
http://ift.tt/2giZkah
Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict chemotherapy outcomes and prognosis in patients with colorectal cancer and synchronous liver metastasis
Abstract
Background
Recent evidence indicates that inflammatory parameters could be useful to predict metastasis from colorectal cancer. However, their roles in predicting chemotherapy response and prognosis in patients with synchronous colorectal liver metastasis (CLM) are unknown.
Methods
The clinical data and baseline laboratory parameters of 55 patients with synchronous CLM were retrospectively reviewed. All patients underwent palliative resection of the primary tumor and oxaliplatin-based chemotherapy. Two indices of systemic inflammation were reviewed—neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)—preoperatively and before the second cycle of chemotherapy. Associations between prognostic variables and tumor response, progression, and survival were investigated.
Results
NLR < 4 and PLR < 150 were correlated with better disease control (p = 0.024 and 0.026, respectively). In univariate analysis, elevated NLR and PLR were significant prognostic factors for poor overall survival (OS) and progression-free survival (PFS). In multivariate analysis, PLR (p = 0.027), age (p = 0.018), resection of liver metastases (p = 0.017), and lactate dehydrogenase level (p = 0.011) were independent predictors of PFS, while resection of liver metastases was the only independent predictor of OS (p = 0.002). In addition, when patients were divided into groups according to changes in NLR and/or PLR, reduced NLR and PLR were associated with improved disease control (p = 0.038 and 0.025, respectively). Normalization of NLR also was associated with improved PFS.
Conclusions
NLR and PLR are potentially useful clinical biomarkers to predict chemotherapy response in patients with synchronous CLM. PLR also may be useful to predict PFS in these patients.
http://ift.tt/2fy36L9
Right hepatectomy for a detoured left hepatic artery in hilar cholangiocarcinoma—report of a rare but rational resection
Abstract
Background
Curative hepatectomy with bile duct resection is the treatment for perihilar cholangiocarcinoma. A locally advanced tumor necessitates hepatectomy with simultaneous vascular resection, and reconstruction remains an obstacle for surgeons. Studies have focused on the variations of hepatic arteries. Nevertheless, the anatomical alignment of the portal veins, bile ducts, and hepatic arteries are equally critical in surgical planning of curative resection for advanced tumors. We have reported promising outcomes of hepatectomy with simultaneous resection and reconstruction of the hepatic artery. With respect to the type of surgery, most patients undergo left hepatectomy with right hepatic artery resection and reconstruction in contrast to right hepatectomy with left hepatic artery resection and reconstruction. We present two patients who showed detoured left hepatic arteries that were invaded by the perihilar tumors.
Case presentation
A 78-year-old man who presented with epigastric pain and abnormal liver function was referred to our clinic for further examination. Serial examination resulted in the diagnosis of Bismuth type II hilar cholangiocarcinoma. The left hepatic artery ran a detoured course and was invaded by the tumor. The second patient was a 76-year-old woman who presented with jaundice and the Bismuth type II hilar cholangiocarcinoma. The left hepatic artery was along the right-lateral position of the left portal vein and was invaded by the tumor. The variant anatomical relationship of the vessel was identified preoperatively in both patients, and they underwent right hepatectomy with concomitant left hepatic artery resection and reconstruction without any major complications or recurrence.
Conclusions
The largely biased selection of patients is based on the following anatomical relationship: the left hepatic artery usually runs left lateral to the portal vein, which spares invasion by the perihilar cholangiocarcinoma. On the contrary, the right hepatic artery mostly runs behind the bile duct and is invaded by the tumor. This aforementioned anatomy is one of the reasons for the relatively rare left hepatic artery resections and reconstructions in right hepatectomies. By meticulous preoperative evaluation with images, we identify the anatomical variation and performed right hepatectomy with concomitant left hepatic artery resection and reconstruction without any major complications and mortalities.
http://ift.tt/2fZTUO7
Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict chemotherapy outcomes and prognosis in patients with colorectal cancer and synchronous liver metastasis
Abstract
Background
Recent evidence indicates that inflammatory parameters could be useful to predict metastasis from colorectal cancer. However, their roles in predicting chemotherapy response and prognosis in patients with synchronous colorectal liver metastasis (CLM) are unknown.
Methods
The clinical data and baseline laboratory parameters of 55 patients with synchronous CLM were retrospectively reviewed. All patients underwent palliative resection of the primary tumor and oxaliplatin-based chemotherapy. Two indices of systemic inflammation were reviewed—neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)—preoperatively and before the second cycle of chemotherapy. Associations between prognostic variables and tumor response, progression, and survival were investigated.
Results
NLR < 4 and PLR < 150 were correlated with better disease control (p = 0.024 and 0.026, respectively). In univariate analysis, elevated NLR and PLR were significant prognostic factors for poor overall survival (OS) and progression-free survival (PFS). In multivariate analysis, PLR (p = 0.027), age (p = 0.018), resection of liver metastases (p = 0.017), and lactate dehydrogenase level (p = 0.011) were independent predictors of PFS, while resection of liver metastases was the only independent predictor of OS (p = 0.002). In addition, when patients were divided into groups according to changes in NLR and/or PLR, reduced NLR and PLR were associated with improved disease control (p = 0.038 and 0.025, respectively). Normalization of NLR also was associated with improved PFS.
Conclusions
NLR and PLR are potentially useful clinical biomarkers to predict chemotherapy response in patients with synchronous CLM. PLR also may be useful to predict PFS in these patients.
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Right hepatectomy for a detoured left hepatic artery in hilar cholangiocarcinoma—report of a rare but rational resection
Abstract
Background
Curative hepatectomy with bile duct resection is the treatment for perihilar cholangiocarcinoma. A locally advanced tumor necessitates hepatectomy with simultaneous vascular resection, and reconstruction remains an obstacle for surgeons. Studies have focused on the variations of hepatic arteries. Nevertheless, the anatomical alignment of the portal veins, bile ducts, and hepatic arteries are equally critical in surgical planning of curative resection for advanced tumors. We have reported promising outcomes of hepatectomy with simultaneous resection and reconstruction of the hepatic artery. With respect to the type of surgery, most patients undergo left hepatectomy with right hepatic artery resection and reconstruction in contrast to right hepatectomy with left hepatic artery resection and reconstruction. We present two patients who showed detoured left hepatic arteries that were invaded by the perihilar tumors.
Case presentation
A 78-year-old man who presented with epigastric pain and abnormal liver function was referred to our clinic for further examination. Serial examination resulted in the diagnosis of Bismuth type II hilar cholangiocarcinoma. The left hepatic artery ran a detoured course and was invaded by the tumor. The second patient was a 76-year-old woman who presented with jaundice and the Bismuth type II hilar cholangiocarcinoma. The left hepatic artery was along the right-lateral position of the left portal vein and was invaded by the tumor. The variant anatomical relationship of the vessel was identified preoperatively in both patients, and they underwent right hepatectomy with concomitant left hepatic artery resection and reconstruction without any major complications or recurrence.
Conclusions
The largely biased selection of patients is based on the following anatomical relationship: the left hepatic artery usually runs left lateral to the portal vein, which spares invasion by the perihilar cholangiocarcinoma. On the contrary, the right hepatic artery mostly runs behind the bile duct and is invaded by the tumor. This aforementioned anatomy is one of the reasons for the relatively rare left hepatic artery resections and reconstructions in right hepatectomies. By meticulous preoperative evaluation with images, we identify the anatomical variation and performed right hepatectomy with concomitant left hepatic artery resection and reconstruction without any major complications and mortalities.
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Evaluation of 18 F-fluorothymidine positron emission tomography ([ 18 F]FLT-PET/CT) methodology in assessing early response to chemotherapy in patients with gastro-oesophageal cancer
Abstract
Background
3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT) PET has limited utility in abdominal imaging due to high physiological hepatic uptake of a tracer. We evaluated [18F]FLT-PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (KSF) to improve tumour visualisation in patients with locally advanced and metastatic gastro-oesophageal cancer and as a marker of early response to chemotherapy.
Dynamic [18F]FLT-PET/CT data were collected before and 3 weeks post first cycle of chemotherapy. Changes in tumour [18F]FLT-PET/CT variables were determined. Response was determined on contrast-enhanced CT after three cycles of therapy using RECIST 1.1.
Results
Ten patients were included. Following application of the KSF, visual distinction of all oesophageal and/or gastric tumours was observed in [18F]FLT-PET images. Among the nine patients available for response evaluation (RECIST 1.1), three patients had responded (partial response) and six patients were non-responders (stable disease). There was a significant association between Ki-67 and all baseline [18F]FLT-PET parameters. Area under the curve (AUC) from 0 to 1 min was associated with treatment response.
Conclusions
The results of this study indicate that application of the KSF allowed accurate visualisation of both primary and metastatic lesions following imaging with the proliferation marker, [18F]FLT-PET/CT. However, [18F]FLT-PET uptake parameters did not correlate with response. Instead, we observe significant changes in tracer delivery following chemotherapy suggesting that further [18F]FLT-PET/CT studies in this tumour type should be undertaken with caution.
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Evaluation of 18 F-fluorothymidine positron emission tomography ([ 18 F]FLT-PET/CT) methodology in assessing early response to chemotherapy in patients with gastro-oesophageal cancer
Abstract
Background
3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT) PET has limited utility in abdominal imaging due to high physiological hepatic uptake of a tracer. We evaluated [18F]FLT-PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (KSF) to improve tumour visualisation in patients with locally advanced and metastatic gastro-oesophageal cancer and as a marker of early response to chemotherapy.
Dynamic [18F]FLT-PET/CT data were collected before and 3 weeks post first cycle of chemotherapy. Changes in tumour [18F]FLT-PET/CT variables were determined. Response was determined on contrast-enhanced CT after three cycles of therapy using RECIST 1.1.
Results
Ten patients were included. Following application of the KSF, visual distinction of all oesophageal and/or gastric tumours was observed in [18F]FLT-PET images. Among the nine patients available for response evaluation (RECIST 1.1), three patients had responded (partial response) and six patients were non-responders (stable disease). There was a significant association between Ki-67 and all baseline [18F]FLT-PET parameters. Area under the curve (AUC) from 0 to 1 min was associated with treatment response.
Conclusions
The results of this study indicate that application of the KSF allowed accurate visualisation of both primary and metastatic lesions following imaging with the proliferation marker, [18F]FLT-PET/CT. However, [18F]FLT-PET uptake parameters did not correlate with response. Instead, we observe significant changes in tracer delivery following chemotherapy suggesting that further [18F]FLT-PET/CT studies in this tumour type should be undertaken with caution.
http://ift.tt/2ghSGAs
Inhibitory effects of lapachol on rat C6 glioma in vitro and in vivo by targeting DNA topoisomerase I and topoisomerase II
Lapachol is a natural naphthoquinone compound that possesses extensive biological activities. The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vi...
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Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer
miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological role and m...
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May High MMP-2 and TIMP-2 Expressions Increase or Decrease the Aggressivity of Oral Cancer?
Abstract
Matrix metalloproteinases-2 (MMP-2) and the tissue inhibitor of metalloproteinase-2 (TIMP-2), may presumably have an important role on the invasion and metastatic spread of malignancies attributed to an uncontrolled degradation of the extracellular matrix (ECM). A retrospective chart analysis was carried out to study the expression of MMP-2 and TIMP-2 on the archival samples of oral squamous cell carcinoma (OSCC) (n = 30) and normal mucosa (n = 10) by immunohistochemistry and compared with the clinicopathologic parameters of cases. Both MMP-2 and TIMP-2 expressions showed a positive correlation with the grades, stages and metastatic capacities of tumors (Spearman's correlation, p < 0.05). Concomitant increase in the expression of TIMP-2 and MMP-2 suggested that the rate of MMP-2/TIMP-2 expression is a better marker for characterization of MMP-2 concentration. High expression and/or activity of MMP-2 were linked with poorer survival in OSCC cases, while TIMPs have been shown to apparently act as either growth-stimulating or suppressor factors for tumors. It was also revealed that MMP-2 and TIMP-2 were secreted by both tumor cells and stromal cells. A new concept, supposing the dynamic, anticancer partnership between the residual genome stabilizer machinery of tumor cells and defensive cells adjacent to tumors, may illuminate the controversial results. In conclusion, the stronger the infiltrative and metastatic capacity of cancers, the higher is the rate of MMP-2/TIMP-2 expression helping the arrival of humoral and cellular anticancer forces.
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Contribution of submandibular gland and swallowing structure sparing to post-radiation therapy PEG dependence in oropharynx cancer patients treated with split-neck IMRT technique
Abstract
Background
Radiation therapy-related dysphagia is worsened by xerostomia. The submandibular glands (SMG) produce saliva rich in lubricating mucins, and sparing the SMG has been shown to reduce xerostomia. The goal of this study was to determine whether SMG sparing IMRT is associated with reduced post-treatment PEG dependence in locally advanced oropharynx cancer patients.
Methods
Patients treated with definitive radiation therapy for oropharynx cancer were included in this retrospective study. Those with disease recurrence were excluded. Salivary glands and swallowing-related organs at risk, including pharyngeal constrictors, were contoured. Primary endpoint was time from end of radiation treatment to freedom from gastrostomy (PEG) tube dependence. Cox proportional hazards regression and logistic regression were used to assess influence of normal tissue doses on swallowing related endpoints.
Results
Sixty-nine patients were included. All had stage III/IV disease and 97% received concurrent systemic therapy. Fifty-seven percent had contralateral SMG (cSMG) mean dose <50 Gy, a level shown to predict for xerostomia. Eighty four percent of patients had a PEG tube placed electively. On univariate analysis, the strongest predictor of time to freedom from PEG tube dependence was cSMG dose (HR 0.97 per Gy (95% CI 0.95–0.98), p < 0.0001). This relationship persisted on multivariate analysis (p = 0.052). The dose to superior and middle pharyngeal constrictor muscles, and larynx were also significant on univariate analysis. Patients with cSMG dose less than median (42 Gy, n = 34) had a significantly shorter time to freedom from PEG dependence: median 1.9 vs. 3.5 months, p < 0.0001. At 6 months, 3% of patients with cSMG dose < 42 Gy were PEG dependent compared to 31% with cSMG dose > 42 Gy (p = 0.002).
Conclusions
Patients treated with cSMG sparing radiotherapy had significantly shorter time to PEG tube removal after treatment, suggesting a clinically meaningful reduction in subacute dysphagia compared to non-cSMG sparing treatment.
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4DCT and CBCT based PTV margin in Stereotactic Body Radiotherapy(SBRT) of non-small cell lung tumor adhered to chest wall or diaphragm
Abstract
Background
Large tumor motion often leads to larger treatment volumes, especially the lung tumor located in lower lobe and adhered to chest wall or diaphragm. The purpose of this work is to investigate the impacts of planning target volume (PTV) margin on Stereotactic Body Radiotherapy (SBRT) in non-small cell lung cancer (NSCLC).
Methods
Subjects include 20 patients with the lung tumor located in lower lobe and adhered to chest wall or diaphragm who underwent SBRT. Four-dimensional computed tomography (4DCT) were acquired at simulation to evaluate the tumor intra-fractional centroid and boundary changes, and Cone-beam Computer Tomography (CBCT) were acquired during each treatment to evaluate the tumor inter-fractional set-up displacement. The margin to compensate for tumor variations uncertainties was calculated with various margin calculated recipes published in the exiting literatures.
Results
The means (±standard deviation) of tumor centroid changes were 0.16 (±0.13) cm, 0.22 (±0.15) cm, and 1.37 (±0.81) cm in RL, AP, and SI directions, respectively. The means (±standard deviation) of tumor edge changes were 0.21 (±0.18) cm, 0.50 (±0.23) cm, and 0.19 (±0.44) cm in RL, AP, and SI directions, respectively. The means (±standard deviation) of tumor set-up displacement were 0.03 (±0.24) cm, 0.02 (±0.26) cm, and 0.02 (±0.43) cm in RL, AP, and SI directions, respectively. The PTV margin to compensate for lung cancer tumor variations uncertainties were 0.88, 0.98 and 2.68 cm in RL, AP and SI directions, which were maximal among all margin recipes.
Conclusions
4DCT and CBCT imaging are appropriate to account for the tumor intra-fractional centroid, boundary variations and inter-fractional set-up displacement. The PTV margin to compensate for lung cancer tumor variations uncertainties can be obtained. Our results show that a conventional 1.0 cm margin in the SI plane dose not suffice to compensate the geometrical variety of the tumor located in lower lobe and adhered to chest wall and diaphragm.
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Evaluation of diagnostic and prognostic significance of Ki-67 index in pulmonary carcinoid tumours
Abstract
Background
Pulmonary carcinoid (PC) tumours are classified as either typical (TC) or atypical (AC) according to mitotic index (MI) and presence of necrosis. The aim of this study was to analyse the diagnostic and prognostic values of the Ki-67 index in PC.
Methods/patients
Between January 2001 and March 2015, we evaluated 94 consecutive patients with a confirmed diagnosis of TC (n = 75) or AC (n = 19) at our institution. Diagnostic histology was centrally reviewed by a local expert neuroendocrine pathologist, with assessment of Ki-67, MI, and necrosis.
Results
Median patient follow-up was 35 months. Eighty-four patients who underwent curative surgical resection were included in the survival analysis for identification of prognostic factors. Ki-67 index showed high diagnostic accuracy to predict histological subtype when assessed by receiver operator characteristic curves with an area under the curve of 0.923 (95% CI 0.852–0.995, p < 0.001). Multivariate analysis showed that MI, Ki-67 index, and the presence or absence of necrosis were independent prognostic factors for relapse-free survival. Combination of MI, Ki-67, and necrosis led to the classification of patients into four different prognostic groups (very low, low, intermediate, and high risks of relapse).
Conclusions
The current study proposes the incorporation of Ki-67 index in the prognostic classification of PC tumours. Due to the limited number of patients and length of follow-up, the current model needs validation by larger cohort studies. Nevertheless, our results suggest that Ki-67 index and MI have continuous effect on prognosis. Prognostic models incorporating multiple cutoffs of Ki-67 and MI might better predict outcome and inform clinical decisions.
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Cardiovascular disease and physical activity in adult cancer survivors: a nested, retrospective study from the Atlantic PATH cohort
Abstract
Purpose
The study aimed to examine the relationship between cardiovascular disease (CVD) and physical activity (PA) levels in cancer survivors (CS).
Methods
Using a nested, retrospective follow-up design, this study presents the self-reported prevalence of CVD in an Atlantic Canadian population-based cohort of 1526 CS and 6034 age-sex matched, non-cancer controls ranging from 35 to 69 years of age. Univariate and multiple logistic regression models were used to explore the association between CVD and PA.
Results
Overall, CS were 30% more likely to have ever experienced a CVD event than controls (OR = 1.3; 95% CI 1–1.7, p = .07). Survivors were also significantly more likely to report having hypertension (OR = 1.60; 95% CI 1.03–1.3, p = .02) and diabetes (OR = 1.27; 95% CI 1.03–1.16, p = .02). Compared to controls, CS were significantly less likely to engage in high levels of PA. For survivors, compared to those who were least physically active, the odds of having a CVD risk factor was 35% lower for those who were moderately active (OR = 0.65; 95% CI 0.48–0.88) and 45% lower in the most highly active group (OR = 0.55; 95% CI 0.4–0.73). For controls, the odds of having a CVD risk factor was 25% lower for those in the moderately active group (OR = 0.75; 95% CI 0.64–0.88) and 30% lower for those in the high active group (OR = 0.70; 95% CI 0.6–0.81).
Conclusion
Low active survivors appear to be at a high risk of CVD-related comorbidity.
Implications for cancer survivors
PA is associated with lower CVD-related comorbidity in CS, suggesting that interventions directed at increasing PA should be implemented to improve long-term health outcomes.
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Harms of Cervical Cancer Screening in the United States and the Netherlands
ABSTRACT
We studied harms related to cervical cancer screening and management of screen-positive women in the United States (US) and the Netherlands. We utilised data from four US integrated health care systems (SEARCH), the US National Health Interview Survey, New Mexico state, the Netherlands national histopathology registry, and included studies on adverse health effects of cervical screening. We compared the number of Papanicolaou (Pap) smear tests, abnormal test results, punch biopsies, treatments, health problems (anxiety, pain, bleeding, and discharge), and preterm births associated with excisional treatments. Results were age-standardized to the 2007 US population. Based on SEARCH, an estimated 36 million Pap tests were performed in 2007 for 91 million US women aged 21-65 years, leading to 2.3 million abnormal Pap tests, 1.5 million punch biopsies, 0.3 million treatments for precancerous lesions, 5 thousand preterm births, and over 8 million health problems. Under Netherlands screening practice, fewer Pap tests (58%), abnormal test results (64%), punch biopsies (75%), treatment procedures (40%), preterm births (60%), and health problems (63%) would have occurred. The SEARCH data did not differ much from other US data for 2007 or from more recent data up to 2013. Thus compared with the less intensive screening practice in the Netherlands, US practice of cervical cancer screening may have resulted in two- to three-fold higher harms, while the effects on cervical cancer incidence and mortality are similar. The results are also of high relevance in making recommendations for HPV screening. Systematic collection of harms data is needed for monitoring and for better incorporation of harms in making screening recommendations. This article is protected by copyright. All rights reserved.
http://ift.tt/2f4u1xv
Evaluation of diagnostic and prognostic significance of Ki-67 index in pulmonary carcinoid tumours
Abstract
Background
Pulmonary carcinoid (PC) tumours are classified as either typical (TC) or atypical (AC) according to mitotic index (MI) and presence of necrosis. The aim of this study was to analyse the diagnostic and prognostic values of the Ki-67 index in PC.
Methods/patients
Between January 2001 and March 2015, we evaluated 94 consecutive patients with a confirmed diagnosis of TC (n = 75) or AC (n = 19) at our institution. Diagnostic histology was centrally reviewed by a local expert neuroendocrine pathologist, with assessment of Ki-67, MI, and necrosis.
Results
Median patient follow-up was 35 months. Eighty-four patients who underwent curative surgical resection were included in the survival analysis for identification of prognostic factors. Ki-67 index showed high diagnostic accuracy to predict histological subtype when assessed by receiver operator characteristic curves with an area under the curve of 0.923 (95% CI 0.852–0.995, p < 0.001). Multivariate analysis showed that MI, Ki-67 index, and the presence or absence of necrosis were independent prognostic factors for relapse-free survival. Combination of MI, Ki-67, and necrosis led to the classification of patients into four different prognostic groups (very low, low, intermediate, and high risks of relapse).
Conclusions
The current study proposes the incorporation of Ki-67 index in the prognostic classification of PC tumours. Due to the limited number of patients and length of follow-up, the current model needs validation by larger cohort studies. Nevertheless, our results suggest that Ki-67 index and MI have continuous effect on prognosis. Prognostic models incorporating multiple cutoffs of Ki-67 and MI might better predict outcome and inform clinical decisions.
http://ift.tt/2fW5cBu
Fixed-Dose Combination of Canagliflozin and Metformin for the Treatment of Type 2 Diabetes: An Overview
Abstract
Metformin is recommended as a first-line therapy for patients with type 2 diabetes mellitus (T2DM). However, many patients do not achieve glycemic goals with metformin monotherapy and require subsequent combination therapy with other antihyperglycemic agents (AHAs). For newly diagnosed patients with high blood glucose, initial combination therapy may be required to achieve glycemic control. The American Association for Clinical Endocrinologists algorithm for the treatment of T2DM recommends metformin plus a sodium glucose co-transporter 2 (SGLT2) inhibitor as the first oral combination in patients who present with HbA1c ≥7.5%. Canagliflozin, an SGLT2 inhibitor, lowers the renal threshold for glucose and increases urinary glucose excretion leading to a mild osmotic diuresis and a net caloric loss. The effect of canagliflozin is insulin-independent and complementary to other AHAs, including metformin. A fixed-dose combination (FDC) of canagliflozin and metformin is also available with variable dosing, which may be attractive to some patients owing to the potential for reduced pill burden and costs. This article reviews the efficacy and safety of canagliflozin in combination with metformin based on data from the canagliflozin phase 3 clinical program. As initial combination therapy in drug-naïve patients or as dual therapy with metformin or triple therapy in combination with metformin and other AHAs, canagliflozin 100 and 300 mg improved glycemic control and provided reductions in body weight and systolic blood pressure that were sustained for up to 104 weeks. Canagliflozin was generally well tolerated across studies in combination with metformin. An increased incidence of adverse events (AEs) related to the mechanism of SGLT2 inhibition (i.e., genital mycotic infections, urinary tract infections, osmotic diuresis-related AEs) was observed with canagliflozin. Canagliflozin was associated with a low incidence of hypoglycemia when not used in conjunction with AHAs associated with hypoglycemia (i.e., insulin or sulfonylurea). Together, these results support the use of a canagliflozin and metformin FDC as a treatment approach for a broad range of patients with T2DM.
Funding: Janssen Scientific Affairs, LLC.
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Impact of Treatment-Related Beliefs on Medication Adherence in Immune-Mediated Inflammatory Diseases: Results of the Global ALIGN Study
Abstract
Introduction
Medication adherence is critical in chronic immune-mediated inflammatory diseases (IMIDs) and could be affected by patients' treatment-related beliefs. The objective of this study was to determine beliefs about systemic medications in patients with IMIDs and to explore the association of those beliefs and other factors with adherence.
Methods
This was a multi-country, cross-sectional, self-administered survey study. Included were adults diagnosed with one of six IMIDs receiving conventional systemic medications and/or tumor necrosis factor inhibitors (TNFi). Patients' necessity beliefs/concerns towards and adherence to treatments were assessed by the Beliefs about Medicines Questionnaire and four-item Morisky Medication Adherence Scale. Correlation of patients' beliefs about treatment and other factors with adherence were evaluated by multivariable regression analyses.
Results
Among studied patients (N = 7197), 32.0% received TNFi monotherapy, 27.7% received TNFi–conventional combination therapy, and 40.3% received conventional medications. Across IMIDs, high adherence to systemic treatment was more prevalent in TNFi groups (61.3–80.7%) versus corresponding conventional treatment groups (28.4–64.7%). In at least four IMIDs, greater perception of the illness continuing forever (P < 0.001), of the treatment helping (P < 0.001), and more concerns about the illness (P < 0.01), but not clinical parameters, were associated with higher treatment necessity beliefs. Higher treatment necessity beliefs, older age, Caucasian race, and TNFi therapy were associated with high medication adherence in at least four IMIDs.
Conclusions
Treatment necessity beliefs were higher than concerns about current medication in patients with IMID. Illness perceptions had a greater impact on treatment necessity beliefs than clinical parameters. Older age, greater treatment necessity beliefs, and TNFi therapy were associated with high self-reported medication adherence in at least four IMIDs.
Trial registration
ACTRN12612000977875.
Funding
AbbVie.
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What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study
BACKGROUND
The purpose of this study was to determine the effect of retroperitoneal (RP) exploration on progression-free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC) patients with stage IIIC disease who underwent optimal debulking surgery.
METHODS
Data were collected from records of the Gynecologic Oncology Group 182 (GOG-182) study of stage IIIC EOC patients cytoreduced to no gross residual disease (R0) or minimal gross residual (<1 cm) disease (MGRD) at primary surgery. Patients with stage IIIC disease by intraperitoneal (IP) tumor were included and divided into 3 groups: 1) > 2 cm IP tumor without lymph node involvement (IP/RP−), 2) > 2 cm IP tumor with lymph node involvement (IP/RP+), and 3) > 2 cm IP tumor with no RP exploration (IP/RP?). The effects of disease distribution and RP exploration on PFS and OS were assessed using Kaplan–Meier and proportional hazards methods.
RESULTS
There were 1871 stage IIIC patients in GOG-182 who underwent optimal primary debulking surgery. Of these, 689 (36.8%) underwent RP exploration with removal of lymph nodes from at least 1 para-aortic site, and 1182 (63.2%) did not. There were 269 patients in the IP/RP− group, 420 patients in the IP/RP + group, and 1182 patients in the IP/RP? group. Improved PFS (18.5 vs 16.0 months; P < .0001) and OS (53.3 vs 42.8 months; P < .0001) were associated with RP exploration versus no exploration. Patients with MGRD had improved PFS (16.8 vs 15.1 months, P = 0.0108) and OS (44.9 vs 40.5 months, P = 0.0076) versus no exploration.
CONCLUSIONS
RP exploration at the time of primary surgery in patients with optimally debulked stage IIIC EOC is associated with a survival benefit. Cancer 2016. © 2016 American Cancer Society.
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Treatment implications of posterior fossa ependymoma subgroups
Abstract
Posterior fossa ependymoma comprises two distinct molecular entities, ependymoma_posterior fossa A (EPN_PFA) and ependymoma_posterior fossa B (EPN_PFB), with differentiable gene expression profiles. As yet, the response of the two entities to treatment is unclear. To determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment, we studied a cohort of 820 patients with molecularly profiled, clinically annotated posterior fossa ependymomas. We found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA, which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis" in the Journal of Clinical Oncology. Patients with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy, whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.
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Induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma
Abstract
The value of adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. In our recent article entitled "Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial" published in the Lancet Oncology, we reported the results of a phase III, multicenter, randomized controlled trial comparing cisplatin, 5-fluorouracil, and docetaxel (TPF) IC plus CCRT versus CCRT alone in patients with T3-4N1/TxN2-3M0 NPC (ClinicalTrials.gov registration number NCT01245959). The IC-plus-CCRT group showed significantly higher 3-year failure-free survival, overall survival, and distant failure-free survival rates than the CCRT-alone group, with an acceptable toxicity profile. Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC. However, long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy, and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.
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Risk of nasopharyngeal carcinoma penetrates across immigrant generations: A migrant cohort study of 2.3 million Jewish Israeli adolescents
Abstract
Nasopharyngeal cancer (NPC) incidence varies widely across geographic regions and ethnic groups. We conducted a large-scale migrant cohort study to assess origin and migrant generation as predictors of NPC, controlling for possible confounders. Data on 2.3 million Jewish Israeli adolescents, who underwent a compulsory general health examination at ages 16–19 between the years 1967–2011 were linked to the Israel National Cancer Registry to obtain incident NPC up to 2012. Cox proportional hazards was used to model time to event. During 46.5 million person-years of follow-up, 276 incident cases were identified. Origin was a strong independent predictor of NPC with high rates for first generation North African born (adjusted HR 5.52; 95% CI 2.43-12.52; p<0.000044) and Asian born (adjusted HR 3.79; 95% CI 1.43-10.00; p=0.007) compared to European-born, adjusted for sex, year of birth, residential socio-economic position, years of education, rural residence, body mass index and height. The magnitude of the associations was similar in the Israeli-born of North African and Asian origin, with these second and third generation immigrants showing elevated HRs (adjusted HR 6.09; 95% CI 2.81-13.20; p=4.72.10−6 and 3.86; 95% CI 1.77-8.41; p=0.00067, respectively).
These findings suggest a strong genetic predisposition and/or efficient cultural transmission of environmental exposures in the etiology of nasopharyngeal cancer. This article is protected by copyright. All rights reserved.
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HPV status and favorable outcome in vulvar squamous cancer
Abstract
It is universally accepted that high-risk human papillomavirus (HR-HPV) is the cause of cervical dysplasia and cancer. More recently it has been shown that HPV is also a marker of clinical outcome in oropharyngeal cancer. However, contemporary information is lacking on both the prevalence of HPV infection in vulvar cancer (VSCC), its precursor lesion, vulvar intraepithelial neoplasia (VIN) and the influence of HPV-status on the prognosis of this malignancy. We have conducted a detailed population-based study to examine rates of progression of VIN to VSCC, type-specific HPV prevalence in vulvar disease and the influence of HPV status on clinical outcome in VSCC. We observed that the age at which women are diagnosed with VSCC is falling and there is a significant time gap between first diagnosis of VIN and progression to invasive disease. HR-HPV infection was detected in 87% (97/112) cases of VIN and 52% cases (32/62) of VSCC. The presence of HR-HPV in squamous intraepithelial lesion was associated with lower rates of progression to invasive cancer (hazard ratio, 0.22, p=0.001). In the adjusted analysis, HR-HPV was associated with improved progression-free survival of VSCC compared to those with HPV negative tumours (hazard ratio, 0.32, p=0.02). This article is protected by copyright. All rights reserved.
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Harms of Cervical Cancer Screening in the United States and the Netherlands
ABSTRACT
We studied harms related to cervical cancer screening and management of screen-positive women in the United States (US) and the Netherlands. We utilised data from four US integrated health care systems (SEARCH), the US National Health Interview Survey, New Mexico state, the Netherlands national histopathology registry, and included studies on adverse health effects of cervical screening. We compared the number of Papanicolaou (Pap) smear tests, abnormal test results, punch biopsies, treatments, health problems (anxiety, pain, bleeding, and discharge), and preterm births associated with excisional treatments. Results were age-standardized to the 2007 US population. Based on SEARCH, an estimated 36 million Pap tests were performed in 2007 for 91 million US women aged 21-65 years, leading to 2.3 million abnormal Pap tests, 1.5 million punch biopsies, 0.3 million treatments for precancerous lesions, 5 thousand preterm births, and over 8 million health problems. Under Netherlands screening practice, fewer Pap tests (58%), abnormal test results (64%), punch biopsies (75%), treatment procedures (40%), preterm births (60%), and health problems (63%) would have occurred. The SEARCH data did not differ much from other US data for 2007 or from more recent data up to 2013. Thus compared with the less intensive screening practice in the Netherlands, US practice of cervical cancer screening may have resulted in two- to three-fold higher harms, while the effects on cervical cancer incidence and mortality are similar. The results are also of high relevance in making recommendations for HPV screening. Systematic collection of harms data is needed for monitoring and for better incorporation of harms in making screening recommendations. This article is protected by copyright. All rights reserved.
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Evaluation of diagnostic and prognostic significance of Ki-67 index in pulmonary carcinoid tumours
Abstract
Background
Pulmonary carcinoid (PC) tumours are classified as either typical (TC) or atypical (AC) according to mitotic index (MI) and presence of necrosis. The aim of this study was to analyse the diagnostic and prognostic values of the Ki-67 index in PC.
Methods/patients
Between January 2001 and March 2015, we evaluated 94 consecutive patients with a confirmed diagnosis of TC (n = 75) or AC (n = 19) at our institution. Diagnostic histology was centrally reviewed by a local expert neuroendocrine pathologist, with assessment of Ki-67, MI, and necrosis.
Results
Median patient follow-up was 35 months. Eighty-four patients who underwent curative surgical resection were included in the survival analysis for identification of prognostic factors. Ki-67 index showed high diagnostic accuracy to predict histological subtype when assessed by receiver operator characteristic curves with an area under the curve of 0.923 (95% CI 0.852–0.995, p < 0.001). Multivariate analysis showed that MI, Ki-67 index, and the presence or absence of necrosis were independent prognostic factors for relapse-free survival. Combination of MI, Ki-67, and necrosis led to the classification of patients into four different prognostic groups (very low, low, intermediate, and high risks of relapse).
Conclusions
The current study proposes the incorporation of Ki-67 index in the prognostic classification of PC tumours. Due to the limited number of patients and length of follow-up, the current model needs validation by larger cohort studies. Nevertheless, our results suggest that Ki-67 index and MI have continuous effect on prognosis. Prognostic models incorporating multiple cutoffs of Ki-67 and MI might better predict outcome and inform clinical decisions.
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Interesting case of base of skull mass infiltrating cavernous sinuses
A man aged 35 years presented with chronic headache and earache of 1-year duration. He had progressive vision loss and diplopia since last 9 months. He also had pain over the face and episodic profuse epistaxis. On examination, perception of light was absent in the right eye and hand movements were detected at 4 m distance in the left eye. Imaging revealed a lobulated mass in the nasopharynx extending into the bilateral cavernous sinuses and sphenoid sinus with bony erosions. Biopsy of the nasopharyngeal mass revealed pathological features which are characteristic of IgG4 disease. His serum IgG4 levels and acute inflammatory markers were also elevated. The patient was started on oral corticosteroid therapy. Fever, headache and earache resolved early and there was gradual improvement in the vision of the left eye. After 6 months, visual acuity in the left eye was 6/9, but right eye visual acuity had no change. Follow-up imaging revealed a significant reduction in the size of the mass.
http://ift.tt/2fgqQjL
Acquired haemophilia A: an unusual postoperative complication
An African-American man aged 65 years with multiple malignancies in remission was admitted for small bowel obstruction. He was treated with laparotomy following failure of conservative management. Postoperatively, he developed intra-abdominal bleed, which persisted, despite surgical haematoma evacuation. Further haematological workup revealed isolated prolongation of activated partial thromboplastin time (aPTT) with reduced factor VIII (FVIII) activity and raised FVIII inhibitor titre. Assuming acquired haemophilia A (AHA), FVIII inhibitor bypassing activity and corticosteroids were started with subsequent resolution of the bleeding from the surgical site. The patient remained free of bleeding episodes at 3-month follow-up and the aPTT normalised. This case report highlights the association of surgery with AHA and summarises the treatments with underlying mechanisms.
http://ift.tt/2eFx7cE
Successful recovery and allogeneic stem cell transplant following chemotherapy-induced severe cardiomyopathy: literature review of management and prognostic factors
Chemotherapy-induced cardiomyopathy is one of the major possible hazards that can result from potential cardiotoxic agents while treating cancer. Prognostic risk factors include the rate of drug administration, history of hypertension, female gender, extremes of age, previous history of mediastinal irradiation, cumulative dose and pre-existing heart disease. Close monitoring of the patients, timely diagnosis, use of well-known biomarkers including cardiac troponins, NT-ProBNP and imaging studies like 2D Echo or cardiac MRI are essential. Emerging biomarkers include carbonyl reductases (CBR1 and CBR3), aldo-keto reductases (AKR, type 1A1, 1C3, 7A2) and topoisomerase2β (Top2β). β blockers and ACE inhibitors have not only been shown to slow down the progression of cardiac dysfunction but also produce symptomatic improvement. Our case report describes a patient with acute myeloblastic leukaemia who developed severe cardiomyopathy acutely after starting the anthracycline-based regimen. Nevertheless, with timely intervention her symptoms improved and subsequently she successfully received allogeneic stem cell transplantation.
http://ift.tt/2fgu4E8
Disseminated Mycobacterium tuberculosis following renal transplant with alemtuzumab induction
Mycobacterium tuberculosis presents unique challenges in the peritransplant period. Here, we describe a case of disseminated tuberculosis following renal transplantation with alemtuzumab induction immunosuppression in a patient with remotely treated pulmonary tuberculosis and ongoing risk factors for re-infection. We also review the available literature regarding the prevalence of tuberculosis infection following solid organ transplant and management of high-risk patients, including the role for isoniazid preventative therapy.
http://ift.tt/2eFAm3M
Disseminated cryptococcosis in an immunocompetent child
Cryptococcus is a ubiquitous fungus and is known for causing meningitis and cutaneous infections in immunocompromised individuals. Disseminated cryptococcal infection is very rare and almost always found to occur in immunocompromised individuals especially in persons infected with HIV. This is particularly attributed to its capsulated spores. But there are few reported cases in which it has been found to cause disseminated infections even in immunocompetent individuals. We report a similar case of disseminated cryptococcal infection in an immunocompetent host. Early detection and treatment of disseminated cryptococcosis is essential to reduce morbidity and for better outcome.
http://ift.tt/2fgqPMJ
Recoverable, Record-High Lactic Acidosis in a Patient with Glycogen Storage Disease Type 1: A Mixed Type A and Type B Lactate Disorder
A 17-year-old patient with GSD type 1a (von Gierke disease) was hospitalized with an extremely elevated serum lactate following an intercurrent infection and interruption of his frequent intake of carbohydrates. The patient developed shock, oliguric renal failure, and cardiorespiratory failure requiring mechanical ventilation and inotropes. At the peak of metabolic decompensation and clinical instability, serum lactate reached a level of 47.6 mmol/L which was accompanied by a severe anion gap metabolic acidosis with a pH of 6.8 and bicarbonate of 4 meq/L. The patient was stabilized with massive infusions of sodium bicarbonate (45 meq/h) and glucose and recovered without the need for dialysis. This patient illustrates pathophysiologic mechanisms involved in the development of extreme mixed type A and type B lactic acidemia, reflecting altered metabolic pathways in GSD type 1, combined with tissue hypoperfusion. The rationale for the specific interventions in this case is outlined.
http://ift.tt/2fwBNkt
Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer
Abstract
Background
miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological role and mechanism remain largely unknown. This study is aimed to study the role of miR-501-5p in the progression of gastric cancer.
Methods
Real-time PCR analysis was used to determine miR-501-5p expression in gastric cancer cell lines, clinical tissues and 112 clinicopathologically characterized gastric cancer specimens. The role of miR-501-5p in maintaining gastric cancer stem cell like phenotype was examined by tumor-sphere formation assay and expression of stem cell markers. Luciferase reporter assay, cellular fractionation and western blot analysis were used to determined that miR-501-5p activated the wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β.
Results
Herein, our results revealed that miR-501-5p was markedly upregulated in gastric cancer cell lines and clinical tissues. High miR-501-5p levels predicted poor overall survival in gastric cancer patients. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-501-5p enhanced the cancer stem cell-like phenotype in gastric cancer cells. Notably,wnt/β-catenin signaling was hyperactivated in gastric cancer cells that overexpress miR-501-5p, and mediated miR-501-5p-induced cancer stem cell-like phenotype. Furthermore, miR-501-5p directly targeted and suppressed multiple repressors of the wnt/β-catenin signaling cascade, including DKK1, NKD1 and GSK3β. These results demonstrate that miR-501-5p maintains constitutively activated wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β, which promotes gastric cancer stem cell like phenotype.
Conclusions
Taken together, our findings reveal a new regulatory mechanism of miR-501-5p and suggest that miR-501-5p might be a potential target in gastric cancer therapy.
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Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer
Abstract
Background
miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological role and mechanism remain largely unknown. This study is aimed to study the role of miR-501-5p in the progression of gastric cancer.
Methods
Real-time PCR analysis was used to determine miR-501-5p expression in gastric cancer cell lines, clinical tissues and 112 clinicopathologically characterized gastric cancer specimens. The role of miR-501-5p in maintaining gastric cancer stem cell like phenotype was examined by tumor-sphere formation assay and expression of stem cell markers. Luciferase reporter assay, cellular fractionation and western blot analysis were used to determined that miR-501-5p activated the wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β.
Results
Herein, our results revealed that miR-501-5p was markedly upregulated in gastric cancer cell lines and clinical tissues. High miR-501-5p levels predicted poor overall survival in gastric cancer patients. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-501-5p enhanced the cancer stem cell-like phenotype in gastric cancer cells. Notably,wnt/β-catenin signaling was hyperactivated in gastric cancer cells that overexpress miR-501-5p, and mediated miR-501-5p-induced cancer stem cell-like phenotype. Furthermore, miR-501-5p directly targeted and suppressed multiple repressors of the wnt/β-catenin signaling cascade, including DKK1, NKD1 and GSK3β. These results demonstrate that miR-501-5p maintains constitutively activated wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β, which promotes gastric cancer stem cell like phenotype.
Conclusions
Taken together, our findings reveal a new regulatory mechanism of miR-501-5p and suggest that miR-501-5p might be a potential target in gastric cancer therapy.
http://ift.tt/2fUSTX3