Haemobilia due to hepatic artery pseudoaneurysm

An 83-year-old woman with a history of hepaticoduodenostomy 20 years ago was admitted with upper gastrointestinal bleeding. Emergency upper gastrointestinal endoscopy revealed multiple blood clots over the stomach and first and second parts of the duodenum. The cannulation of the biliary tree with a flexible end-viewing endoscope exposed the presence of blood clot inside biliary lumen and a semipedunculated polyp which, at first, appeared to be the cause of haemorrhage. A few days after polypectomy, patient was discharged home, however, was admitted again with massive bleeding and selective angiography demonstrated a pseudoaneurysm of left hepatic artery. Angioembolisation was performed and haemorrhage was stopped afterwards.

http://ift.tt/2s8OIwB

Impaired immune function in children and adults with Fanconi anemia

Abstract

Background

Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA.

Procedure

We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls.

Results

Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P < 0.001), lower memory B cells (P < 0.001), and decreased IgM (P < 0.001) but normal IgG. NK cells (P < 0.001) and NK cytotoxicity (P < 0.001) were decreased. CD4⁺ T cells were decreased (P = 0.022), while CD8⁺ T cell and absolute T-cell numbers were comparable. Cytotoxic T cells (P < 0.003), and antigen proliferation response to tetanus (P = 0.019) and candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8⁺ T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA.

Conclusions

Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development.

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Identifying metrics of success for transitional care practices in childhood cancer survivorship: A qualitative study of survivorship providers

Abstract

Background

Long-term survival in childhood cancer is excellent. Most survivors will have a therapy-related chronic condition, yet very few receive survivor-focused care as they transition from adolescence to young adulthood. The purpose of this study is to identify indicators of success in current transitional care practices for young adult survivors of childhood cancer as defined by all members of survivorship care teams.

Procedure

An exploratory, phenomenologic qualitative study was conducted with key informants from medical teams involved in transitional care of childhood cancer survivors. Data were collected through phone interviews with providers from both pediatric and adult care settings.

Results

A multidisciplinary study sample of 29 participants from three institutions identified two major themes with multiple subthemes. The first major theme was that providers must be good communicators, and it emphasized the importance of having good relationships throughout the transition of care to optimize effective communication. The second major theme was that models of care must include well-established partners throughout the healthcare system that promote accessible subspecialty care with streamlined referrals and patient navigation services.

Conclusions

From the perspective of experienced pediatric- and adult-centered providers at three different institutions delivering life-long transitional care for childhood cancer survivors, the optimal model of care must be built around facilitating communication among all key stakeholders and emphasizing patient-friendly services that minimize patient stressors.

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Impaired immune function in children and adults with Fanconi anemia

Abstract

Background

Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA.

Procedure

We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls.

Results

Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P < 0.001), lower memory B cells (P < 0.001), and decreased IgM (P < 0.001) but normal IgG. NK cells (P < 0.001) and NK cytotoxicity (P < 0.001) were decreased. CD4⁺ T cells were decreased (P = 0.022), while CD8⁺ T cell and absolute T-cell numbers were comparable. Cytotoxic T cells (P < 0.003), and antigen proliferation response to tetanus (P = 0.019) and candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8⁺ T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA.

Conclusions

Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development.

http://ift.tt/2r6i0gV

Identifying metrics of success for transitional care practices in childhood cancer survivorship: A qualitative study of survivorship providers

Abstract

Background

Long-term survival in childhood cancer is excellent. Most survivors will have a therapy-related chronic condition, yet very few receive survivor-focused care as they transition from adolescence to young adulthood. The purpose of this study is to identify indicators of success in current transitional care practices for young adult survivors of childhood cancer as defined by all members of survivorship care teams.

Procedure

An exploratory, phenomenologic qualitative study was conducted with key informants from medical teams involved in transitional care of childhood cancer survivors. Data were collected through phone interviews with providers from both pediatric and adult care settings.

Results

A multidisciplinary study sample of 29 participants from three institutions identified two major themes with multiple subthemes. The first major theme was that providers must be good communicators, and it emphasized the importance of having good relationships throughout the transition of care to optimize effective communication. The second major theme was that models of care must include well-established partners throughout the healthcare system that promote accessible subspecialty care with streamlined referrals and patient navigation services.

Conclusions

From the perspective of experienced pediatric- and adult-centered providers at three different institutions delivering life-long transitional care for childhood cancer survivors, the optimal model of care must be built around facilitating communication among all key stakeholders and emphasizing patient-friendly services that minimize patient stressors.

http://ift.tt/2qB2NRx

Giant cell tumor in the sphenoid sinus and ethmoid sinus during childhood, and it is thought that optic atrophy was caused by compressive optic neuropathy.

http://orlhealth.blogspot.com/2017/05/giant-cell-tumor-in-sphenoid-sinus-and.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

The Cisplatin Total Dose and Concomitant Radiation in Locoregionally Advanced Head and Neck Cancer: Any Recent Evidence for Dose Efficacy?

Opinion statement

Concurrent chemoradiotherapy (CRT) with high-dose (100 mg/m²), single-agent cisplatin is considered the standard of care for locoregionally advanced head and neck cancer (LAHNC). Poor compliance often due to significant treatment-related toxicities observed during CRT regimen has stimulated research efforts to examine for evidence of the optimal cumulative cisplatin dose and schedule. The findings from this systematic literature review demonstrate that there are insufficient prospective, randomized controlled data to determine the optimal total dose (and schedule) of cisplatin to administer concomitantly with radiotherapy in the treatment of LAHNC. Given the clinical challenges associated with administering concurrent CRT with single-agent high-dose cisplatin, as well as the long-term toxicities accompanying this treatment, an examination of the available literature for evidence of dose efficacy is of continued clinical interest. Moving forward, it is critical that researchers include complete descriptions of key disease and treatment variables (i.e. treatment compliance and HPV status) to inform and strengthen clinical decisions. The substantial heterogeneity of LAHNC has led to the focus of recent research efforts to risk-stratify using a combination of clinical and molecular markers (e.g. HPV status). Thus, the optimal total dose (and schedule) of cisplatin may need to be modified to reflect the specific characteristics of the individual patient subpopulations being treated. At present, CRT remains the standard of care for LAHNC, but this field is rapidly evolving. National and international clinical trials are ongoing to evaluate treatment de-intensification in favourable risk patient subsets and treatment intensification in poor-risk patient subsets, these will provide evidence-based guidance to individualize therapy with the ultimate goal of improving patient outcomes.

http://ift.tt/2qvl4k7

Overview of the 8th Edition TNM Classification for Head and Neck Cancer

Opinion Statement

The main purpose of the TNM system is to provide an anatomic-based classification to adequately depict cancer prognosis. Accurate cancer staging is important for treatment selection and outcome prediction, research design, and cancer control activities. To maintain clinical relevance, periodical updates to TNM are necessary. The recently published 8th edition TNM classification institutes the following changes to the staging of head and neck (excluding thyroid cancer): new stage classifications [HPV-related oropharyngeal cancer (HPV+ OPC) and soft tissue sarcoma of the head and neck (HN-STS)] and modification of T and N categories [T and N categories for nasopharyngeal cancer (NPC), T categories for oral cavity squamous cell carcinomas (OSCC), N categories for non-viral related head and neck cancer and unknown primary (CUP), and T categories for head and neck cutaneous carcinoma]. These changes reflect better understanding tumor biology and clinical behavior (e.g., HPV+ OPC and HN-STS), improved outcomes associated with technical advances in diagnosis and treatment (e.g., NPC), evolving knowledge about additional prognostic factors and risk stratification from research and observation (e.g., inclusion of depth of invasion variable for OSCC, inclusion of extranodal extension variable for all non-viral head and neck cancer, and reintroduction of size criteria for non-Merkel cell cutaneous carcinoma of the head and neck). This review summarizes the changes and potential advantages and limitations/caveats associated with them. Further evidence is needed to evaluate whether these changes would result in improvement in TNM stage performance to better serve the needs for clinical care, research, and cancer control.

http://ift.tt/2rOYvdV

The Cisplatin Total Dose and Concomitant Radiation in Locoregionally Advanced Head and Neck Cancer: Any Recent Evidence for Dose Efficacy?

Opinion statement

Concurrent chemoradiotherapy (CRT) with high-dose (100 mg/m²), single-agent cisplatin is considered the standard of care for locoregionally advanced head and neck cancer (LAHNC). Poor compliance often due to significant treatment-related toxicities observed during CRT regimen has stimulated research efforts to examine for evidence of the optimal cumulative cisplatin dose and schedule. The findings from this systematic literature review demonstrate that there are insufficient prospective, randomized controlled data to determine the optimal total dose (and schedule) of cisplatin to administer concomitantly with radiotherapy in the treatment of LAHNC. Given the clinical challenges associated with administering concurrent CRT with single-agent high-dose cisplatin, as well as the long-term toxicities accompanying this treatment, an examination of the available literature for evidence of dose efficacy is of continued clinical interest. Moving forward, it is critical that researchers include complete descriptions of key disease and treatment variables (i.e. treatment compliance and HPV status) to inform and strengthen clinical decisions. The substantial heterogeneity of LAHNC has led to the focus of recent research efforts to risk-stratify using a combination of clinical and molecular markers (e.g. HPV status). Thus, the optimal total dose (and schedule) of cisplatin may need to be modified to reflect the specific characteristics of the individual patient subpopulations being treated. At present, CRT remains the standard of care for LAHNC, but this field is rapidly evolving. National and international clinical trials are ongoing to evaluate treatment de-intensification in favourable risk patient subsets and treatment intensification in poor-risk patient subsets, these will provide evidence-based guidance to individualize therapy with the ultimate goal of improving patient outcomes.

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via IFTTT

Overview of the 8th Edition TNM Classification for Head and Neck Cancer

Opinion Statement

The main purpose of the TNM system is to provide an anatomic-based classification to adequately depict cancer prognosis. Accurate cancer staging is important for treatment selection and outcome prediction, research design, and cancer control activities. To maintain clinical relevance, periodical updates to TNM are necessary. The recently published 8th edition TNM classification institutes the following changes to the staging of head and neck (excluding thyroid cancer): new stage classifications [HPV-related oropharyngeal cancer (HPV+ OPC) and soft tissue sarcoma of the head and neck (HN-STS)] and modification of T and N categories [T and N categories for nasopharyngeal cancer (NPC), T categories for oral cavity squamous cell carcinomas (OSCC), N categories for non-viral related head and neck cancer and unknown primary (CUP), and T categories for head and neck cutaneous carcinoma]. These changes reflect better understanding tumor biology and clinical behavior (e.g., HPV+ OPC and HN-STS), improved outcomes associated with technical advances in diagnosis and treatment (e.g., NPC), evolving knowledge about additional prognostic factors and risk stratification from research and observation (e.g., inclusion of depth of invasion variable for OSCC, inclusion of extranodal extension variable for all non-viral head and neck cancer, and reintroduction of size criteria for non-Merkel cell cutaneous carcinoma of the head and neck). This review summarizes the changes and potential advantages and limitations/caveats associated with them. Further evidence is needed to evaluate whether these changes would result in improvement in TNM stage performance to better serve the needs for clinical care, research, and cancer control.

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Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype

Abstract

The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15–140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24–3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype.

http://ift.tt/2rhWBBS

Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype

Abstract

The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15–140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24–3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype.

from Cancer via ola Kala on Inoreader http://ift.tt/2rhWBBS
via IFTTT

Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype

Abstract

The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15–140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24–3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype.

http://ift.tt/2rhWBBS

Longitudinal study of quality of life in advanced cancer patients on home parenteral nutrition

Abstract

Since there is little knowledge regarding the quality of life (QoL) of cancer patients on home parenteral nutrition (HPN), we planned a prospective, longitudinal, double-center study to investigate the changes of QoL in these patients. One hundred and eleven adult cancer patients who were candidates for HPN following the indications of the European guidelines were consecutively enrolled. For QoL analysis, EORTC QLQ-C30 questionnaires were filled at the HPN start and after 1, 2, 3, and 4 months, and scores changes over time were analyzed according to the univariate mixed-effects linear model for repeated measures. Most patients had gastrointestinal cancers, were severely malnourished, and were in stage IV; two-thirds were still receiving oncologic treatments. Median weight loss over 3 months and body mass index were 11.7% and 20.7, respectively. Median survival was 4.7 (1–42) months; 67 and 34% of patients survived 3 and 6 months, respectively. Global QoL, physical functioning, role functioning, emotional functioning, appetite loss, and fatigue scores had a statistically significant trend over time (P < 0.001, P < 0.001, P = 0.007, P < 0.001, P = 0.004, P = 0.022, respectively). At the univariate analyses, the determinants significantly associated with changes in trend over time for physical, role, and emotional functioning were oncologic treatments (P < 0.001, P = 0.014, P = 0.040, respectively) and for appetite loss they were weight loss and Karnofsky performance status (P = 0.003, P = 0.023, respectively). Global QoL, physical, role, and emotional functioning improved during HPN even in advanced cancer patients on oncologic treatments.

In this prospective, longitudinal study that included 111 adults advanced cancer patients, global quality of life, physical functioning, role functioning, and emotional functioning had a statistically significant trend over time. At the univariate analyses, the determinants significantly associated with changes in trend over time for physical, role, and emotional functioning were oncologic treatments. Global quality of life improved during home parenteral nutrition even in advanced cancer patients on oncologic treatments.

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via IFTTT

Longitudinal study of quality of life in advanced cancer patients on home parenteral nutrition

Abstract

Since there is little knowledge regarding the quality of life (QoL) of cancer patients on home parenteral nutrition (HPN), we planned a prospective, longitudinal, double-center study to investigate the changes of QoL in these patients. One hundred and eleven adult cancer patients who were candidates for HPN following the indications of the European guidelines were consecutively enrolled. For QoL analysis, EORTC QLQ-C30 questionnaires were filled at the HPN start and after 1, 2, 3, and 4 months, and scores changes over time were analyzed according to the univariate mixed-effects linear model for repeated measures. Most patients had gastrointestinal cancers, were severely malnourished, and were in stage IV; two-thirds were still receiving oncologic treatments. Median weight loss over 3 months and body mass index were 11.7% and 20.7, respectively. Median survival was 4.7 (1–42) months; 67 and 34% of patients survived 3 and 6 months, respectively. Global QoL, physical functioning, role functioning, emotional functioning, appetite loss, and fatigue scores had a statistically significant trend over time (P < 0.001, P < 0.001, P = 0.007, P < 0.001, P = 0.004, P = 0.022, respectively). At the univariate analyses, the determinants significantly associated with changes in trend over time for physical, role, and emotional functioning were oncologic treatments (P < 0.001, P = 0.014, P = 0.040, respectively) and for appetite loss they were weight loss and Karnofsky performance status (P = 0.003, P = 0.023, respectively). Global QoL, physical, role, and emotional functioning improved during HPN even in advanced cancer patients on oncologic treatments.

In this prospective, longitudinal study that included 111 adults advanced cancer patients, global quality of life, physical functioning, role functioning, and emotional functioning had a statistically significant trend over time. At the univariate analyses, the determinants significantly associated with changes in trend over time for physical, role, and emotional functioning were oncologic treatments. Global quality of life improved during home parenteral nutrition even in advanced cancer patients on oncologic treatments.

http://ift.tt/2qtYaxF

Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer

Background and Objectives

Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy.

Methods

A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin.

Results

The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls.

Conclusions

Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit.

from Cancer via ola Kala on Inoreader http://ift.tt/2qwgB0x
via IFTTT

Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: A pilot study

Background

The significance of inflammation based scores including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and plasma fibrinogen remains unclear in medullary thyroid carcinoma (MTC). We aimed to compare the prognostic value of these scores.

Methods

Seventy-eight patients newly diagnosed as MTC with operation in our institution from May 2009 to September 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were calculated to compare the prognostic value of these scores.

Results

Increased PLR was predictive of lymph node metastasis (AUC = 0.644, P = 0.022), capsule invasion (AUC = 0.666, P = 0.007), advanced tumor stages (AUC = 0.657, P = 0.011), and recurrence (AUC = 0.655, P = 0.049). Increased fibrinogen was predictive of lymph node metastasis (AUC = 0.669, P = 0.006) and capsule invasion (AUC = 0.631, P = 0.038). Reduced PNI was predictive of recurrence (AUC = 0.655, P = 0.049). Kaplan-Meier analyses and Cox regression analysis revealed that PLR was a significant predictor for recurrence.

Conclusions

PLR, fibrinogen, and PNI are all predictive. Specially, PLR is superior to other inflammation based scores in terms of prognostic ability.

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Recurrence patterns of retroperitoneal leiomyosarcoma and impact of salvage surgery

Background

Optimal treatment strategies for retroperitoneal leiomyosarcoma (RPLMS), particularly recurrent disease, are unknown.

Methods

We searched the tumor registry at The University of Texas MD Anderson Cancer Center (MDACC) to identify patients with RPLMS treated between 1994 and 2013.

Results

We identified 172 patients with a diagnosis of a RPLMS. Among the 85 patients who underwent complete resection included in the survival analysis, the median overall survival (OS) was 8.3 years (95% confidence interval [CI], 5.7-12.3), 5-year local recurrence rate was 21%, and 5-year distant metastasis rate was 47%. Among 114 patients who experienced recurrence, patients who underwent salvage surgery for recurrent disease had longer OS after recurrence than patients who did not undergo salvage surgery (median survival after recurrence 5.6 vs 3.3 years, 3-year OS rates after recurrence 72.6% vs 58.1%, HR 0.402 [95%CI, 0.243-0.666]; P = 0.0004). Whether salvage surgery was performed for local or distant recurrence was not associated with OS. Patients who had a longer disease-free interval (≥12 months) had better progression-free survival after salvage surgery than those who had a shorter interval (HR, 0.437 [95%CI, 0.244-0.783]; P = 0.0055).

Conclusions

We recommend that salvage surgery be considered for selected patients with local or distant recurrence of RP LMS.

from Cancer via ola Kala on Inoreader http://ift.tt/2qwgC4B
via IFTTT

Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer

Background and Objectives

Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy.

Methods

A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin.

Results

The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls.

Conclusions

Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit.

http://ift.tt/2qwgB0x

Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: A pilot study

Background

The significance of inflammation based scores including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and plasma fibrinogen remains unclear in medullary thyroid carcinoma (MTC). We aimed to compare the prognostic value of these scores.

Methods

Seventy-eight patients newly diagnosed as MTC with operation in our institution from May 2009 to September 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were calculated to compare the prognostic value of these scores.

Results

Increased PLR was predictive of lymph node metastasis (AUC = 0.644, P = 0.022), capsule invasion (AUC = 0.666, P = 0.007), advanced tumor stages (AUC = 0.657, P = 0.011), and recurrence (AUC = 0.655, P = 0.049). Increased fibrinogen was predictive of lymph node metastasis (AUC = 0.669, P = 0.006) and capsule invasion (AUC = 0.631, P = 0.038). Reduced PNI was predictive of recurrence (AUC = 0.655, P = 0.049). Kaplan-Meier analyses and Cox regression analysis revealed that PLR was a significant predictor for recurrence.

Conclusions

PLR, fibrinogen, and PNI are all predictive. Specially, PLR is superior to other inflammation based scores in terms of prognostic ability.

http://ift.tt/2rPL65h

Recurrence patterns of retroperitoneal leiomyosarcoma and impact of salvage surgery

Background

Optimal treatment strategies for retroperitoneal leiomyosarcoma (RPLMS), particularly recurrent disease, are unknown.

Methods

We searched the tumor registry at The University of Texas MD Anderson Cancer Center (MDACC) to identify patients with RPLMS treated between 1994 and 2013.

Results

We identified 172 patients with a diagnosis of a RPLMS. Among the 85 patients who underwent complete resection included in the survival analysis, the median overall survival (OS) was 8.3 years (95% confidence interval [CI], 5.7-12.3), 5-year local recurrence rate was 21%, and 5-year distant metastasis rate was 47%. Among 114 patients who experienced recurrence, patients who underwent salvage surgery for recurrent disease had longer OS after recurrence than patients who did not undergo salvage surgery (median survival after recurrence 5.6 vs 3.3 years, 3-year OS rates after recurrence 72.6% vs 58.1%, HR 0.402 [95%CI, 0.243-0.666]; P = 0.0004). Whether salvage surgery was performed for local or distant recurrence was not associated with OS. Patients who had a longer disease-free interval (≥12 months) had better progression-free survival after salvage surgery than those who had a shorter interval (HR, 0.437 [95%CI, 0.244-0.783]; P = 0.0055).

Conclusions

We recommend that salvage surgery be considered for selected patients with local or distant recurrence of RP LMS.

http://ift.tt/2qwgC4B

Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer

Background and Objectives

Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy.

Methods

A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin.

Results

The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls.

Conclusions

Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit.

http://ift.tt/2qwgB0x

Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: A pilot study

Background

The significance of inflammation based scores including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and plasma fibrinogen remains unclear in medullary thyroid carcinoma (MTC). We aimed to compare the prognostic value of these scores.

Methods

Seventy-eight patients newly diagnosed as MTC with operation in our institution from May 2009 to September 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were calculated to compare the prognostic value of these scores.

Results

Increased PLR was predictive of lymph node metastasis (AUC = 0.644, P = 0.022), capsule invasion (AUC = 0.666, P = 0.007), advanced tumor stages (AUC = 0.657, P = 0.011), and recurrence (AUC = 0.655, P = 0.049). Increased fibrinogen was predictive of lymph node metastasis (AUC = 0.669, P = 0.006) and capsule invasion (AUC = 0.631, P = 0.038). Reduced PNI was predictive of recurrence (AUC = 0.655, P = 0.049). Kaplan-Meier analyses and Cox regression analysis revealed that PLR was a significant predictor for recurrence.

Conclusions

PLR, fibrinogen, and PNI are all predictive. Specially, PLR is superior to other inflammation based scores in terms of prognostic ability.

http://ift.tt/2rPL65h

Recurrence patterns of retroperitoneal leiomyosarcoma and impact of salvage surgery

Background

Optimal treatment strategies for retroperitoneal leiomyosarcoma (RPLMS), particularly recurrent disease, are unknown.

Methods

We searched the tumor registry at The University of Texas MD Anderson Cancer Center (MDACC) to identify patients with RPLMS treated between 1994 and 2013.

Results

We identified 172 patients with a diagnosis of a RPLMS. Among the 85 patients who underwent complete resection included in the survival analysis, the median overall survival (OS) was 8.3 years (95% confidence interval [CI], 5.7-12.3), 5-year local recurrence rate was 21%, and 5-year distant metastasis rate was 47%. Among 114 patients who experienced recurrence, patients who underwent salvage surgery for recurrent disease had longer OS after recurrence than patients who did not undergo salvage surgery (median survival after recurrence 5.6 vs 3.3 years, 3-year OS rates after recurrence 72.6% vs 58.1%, HR 0.402 [95%CI, 0.243-0.666]; P = 0.0004). Whether salvage surgery was performed for local or distant recurrence was not associated with OS. Patients who had a longer disease-free interval (≥12 months) had better progression-free survival after salvage surgery than those who had a shorter interval (HR, 0.437 [95%CI, 0.244-0.783]; P = 0.0055).

Conclusions

We recommend that salvage surgery be considered for selected patients with local or distant recurrence of RP LMS.

http://ift.tt/2qwgC4B

An evaluation of motion mitigation techniques for pancreatic SBRT

Ablative radiation therapy can be beneficial for pancreatic cancer, and motion mitigation helps to reduce dose to nearby organs-at-risk. Here, we compared two competing methods of motion mitigation—abdominal compression and respiratory gating.

http://ift.tt/2sfl2NC

In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells

Abstract

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34⁺ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10⁸ pDC can be produced from a typical cord blood unit. Blocking the aryl hydrocarbon receptor (AHR) pathway significantly increased the yield of pDC. When compared to pDC isolated from peripheral blood, in vitro differentiated pDC (ivD-pDC) exhibited an increased capacity to induce NK cell-mediated killing of ALL. Although ivD-pDC produced lower amounts of IFN-α than peripheral blood pDC upon TLR activation, they produced more IFN-λ2, known to play a critical role in the induction of anti-tumoral NK cell functions. Both TLR-9 and TLR-7 ligands triggered pDC-induced NK cell activation, offering the possibility to use any clinical-grade TLR-7 or TLR-9 ligands in future clinical trials. Finally, adoptive transfer of ivD-pDC cultured in the presence of an AHR antagonist cured humanized mice with minimal ALL disease. Collectively, our results pave the way to clinical-grade production of sufficient numbers of human pDC for innate immunotherapy against ALL and other refractory malignancies.

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Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome

Abstract

Lynch syndrome is an autosomal dominant condition caused by pathogenic mutations in the DNA mismatch repair (MMR) genes. Although commonly associated with clinical features such as intellectual disability and congenital anomalies, contiguous gene deletions may also result in cancer predisposition syndromes. We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anastomosis for a pT3N1 sigmoid adenocarcinoma. Germline genetic testing of the MSH2, MSH6, and EPCAM genes revealed full gene deletions. SNP-array based DNA copy number analysis identified a deletion of 4.8 Mb at 2p16.3-p21. In addition to the three Lynch syndrome associated genes, the deleted chromosomal section encompassed genes including NRXN1, CRIPT, CALM2, FBXO11, LHCGR, MCFD2, TTC7A, EPAS1, PRKCE, and 15 others. Contiguous gene deletions have been described in other inherited cancer predisposition syndromes, such as Familial Adenomatous Polyposis. Our report and review of the literature suggests that contiguous gene deletion within the 2p16-p21 chromosomal region is a rare cause of Lynch syndrome, but presents with distinct phenotypic features, highlighting the need for recognition and awareness of this syndromic entity.

http://ift.tt/2qvC2id

The Cisplatin Total Dose and Concomitant Radiation in Locoregionally Advanced Head and Neck Cancer: Any Recent Evidence for Dose Efficacy?

Opinion statement

Concurrent chemoradiotherapy (CRT) with high-dose (100 mg/m²), single-agent cisplatin is considered the standard of care for locoregionally advanced head and neck cancer (LAHNC). Poor compliance often due to significant treatment-related toxicities observed during CRT regimen has stimulated research efforts to examine for evidence of the optimal cumulative cisplatin dose and schedule. The findings from this systematic literature review demonstrate that there are insufficient prospective, randomized controlled data to determine the optimal total dose (and schedule) of cisplatin to administer concomitantly with radiotherapy in the treatment of LAHNC. Given the clinical challenges associated with administering concurrent CRT with single-agent high-dose cisplatin, as well as the long-term toxicities accompanying this treatment, an examination of the available literature for evidence of dose efficacy is of continued clinical interest. Moving forward, it is critical that researchers include complete descriptions of key disease and treatment variables (i.e. treatment compliance and HPV status) to inform and strengthen clinical decisions. The substantial heterogeneity of LAHNC has led to the focus of recent research efforts to risk-stratify using a combination of clinical and molecular markers (e.g. HPV status). Thus, the optimal total dose (and schedule) of cisplatin may need to be modified to reflect the specific characteristics of the individual patient subpopulations being treated. At present, CRT remains the standard of care for LAHNC, but this field is rapidly evolving. National and international clinical trials are ongoing to evaluate treatment de-intensification in favourable risk patient subsets and treatment intensification in poor-risk patient subsets, these will provide evidence-based guidance to individualize therapy with the ultimate goal of improving patient outcomes.

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Overview of the 8th Edition TNM Classification for Head and Neck Cancer

Opinion Statement

The main purpose of the TNM system is to provide an anatomic-based classification to adequately depict cancer prognosis. Accurate cancer staging is important for treatment selection and outcome prediction, research design, and cancer control activities. To maintain clinical relevance, periodical updates to TNM are necessary. The recently published 8th edition TNM classification institutes the following changes to the staging of head and neck (excluding thyroid cancer): new stage classifications [HPV-related oropharyngeal cancer (HPV+ OPC) and soft tissue sarcoma of the head and neck (HN-STS)] and modification of T and N categories [T and N categories for nasopharyngeal cancer (NPC), T categories for oral cavity squamous cell carcinomas (OSCC), N categories for non-viral related head and neck cancer and unknown primary (CUP), and T categories for head and neck cutaneous carcinoma]. These changes reflect better understanding tumor biology and clinical behavior (e.g., HPV+ OPC and HN-STS), improved outcomes associated with technical advances in diagnosis and treatment (e.g., NPC), evolving knowledge about additional prognostic factors and risk stratification from research and observation (e.g., inclusion of depth of invasion variable for OSCC, inclusion of extranodal extension variable for all non-viral head and neck cancer, and reintroduction of size criteria for non-Merkel cell cutaneous carcinoma of the head and neck). This review summarizes the changes and potential advantages and limitations/caveats associated with them. Further evidence is needed to evaluate whether these changes would result in improvement in TNM stage performance to better serve the needs for clinical care, research, and cancer control.

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Paradigm shift of therapeutic management of brain metastases in EGFR-mutant non-small cell lung cancer in the era of targeted therapy

Abstract

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations commonly present brain metastases (BM) at the time of NSCLC diagnosis or during the clinical course. Conventionally, the prognosis of BM has been extremely poor, but the advent of EGFR-tyrosine kinase inhibitors (TKIs) has drastically improved the prognosis in these patients. Despite the presence of the blood–brain barrier, EGFR-TKIs have dramatic therapeutic effects on both BM and extracranial disease. In addition, recent systemic chemotherapies reportedly play a role in controlling BM. These treatment modalities can potentially replace whole brain radiotherapy (WBRT) to prevent or delay neurocognitive decline. Therefore, how to utilize these treatments is one issue. The other issue is what kind of treatment is best for recurrence after TKI therapy. Recent reports have shown a positive effect of a combination therapy of EGFR-TKI and radiotherapy on BM. Although neurocognitive decline is underscored when WBRT is considered, a survival benefit from WBRT has been proven especially in the potential long survivors with good prognostic index, especially disease-specific graded prognostic index (DS-GPA). In this review, treatment strategy including chemotherapeutic agents and radiotherapy is discussed in terms of risk–benefit balance in conjunction with DS-GPA.

http://ift.tt/2rgdxsv

Paradigm shift of therapeutic management of brain metastases in EGFR-mutant non-small cell lung cancer in the era of targeted therapy

Abstract

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations commonly present brain metastases (BM) at the time of NSCLC diagnosis or during the clinical course. Conventionally, the prognosis of BM has been extremely poor, but the advent of EGFR-tyrosine kinase inhibitors (TKIs) has drastically improved the prognosis in these patients. Despite the presence of the blood–brain barrier, EGFR-TKIs have dramatic therapeutic effects on both BM and extracranial disease. In addition, recent systemic chemotherapies reportedly play a role in controlling BM. These treatment modalities can potentially replace whole brain radiotherapy (WBRT) to prevent or delay neurocognitive decline. Therefore, how to utilize these treatments is one issue. The other issue is what kind of treatment is best for recurrence after TKI therapy. Recent reports have shown a positive effect of a combination therapy of EGFR-TKI and radiotherapy on BM. Although neurocognitive decline is underscored when WBRT is considered, a survival benefit from WBRT has been proven especially in the potential long survivors with good prognostic index, especially disease-specific graded prognostic index (DS-GPA). In this review, treatment strategy including chemotherapeutic agents and radiotherapy is discussed in terms of risk–benefit balance in conjunction with DS-GPA.

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In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells

Abstract

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34⁺ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10⁸ pDC can be produced from a typical cord blood unit. Blocking the aryl hydrocarbon receptor (AHR) pathway significantly increased the yield of pDC. When compared to pDC isolated from peripheral blood, in vitro differentiated pDC (ivD-pDC) exhibited an increased capacity to induce NK cell-mediated killing of ALL. Although ivD-pDC produced lower amounts of IFN-α than peripheral blood pDC upon TLR activation, they produced more IFN-λ2, known to play a critical role in the induction of anti-tumoral NK cell functions. Both TLR-9 and TLR-7 ligands triggered pDC-induced NK cell activation, offering the possibility to use any clinical-grade TLR-7 or TLR-9 ligands in future clinical trials. Finally, adoptive transfer of ivD-pDC cultured in the presence of an AHR antagonist cured humanized mice with minimal ALL disease. Collectively, our results pave the way to clinical-grade production of sufficient numbers of human pDC for innate immunotherapy against ALL and other refractory malignancies.

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Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4⁺ and CD8⁺, FOXP3⁺CD25^bright Treg, and "innate-like" CD56⁺) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4⁺ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4⁺ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4⁺ and CD8⁺ T cell subsets associated with higher frequencies of IFNγ⁺ and GrzB⁺ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

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Ethical considerations of neuro-oncology trial design in the era of precision medicine

Abstract

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

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Assessment of airway compression on chest radiographs in children with pulmonary tuberculosis

Abstract

Background

Because small, pliable paediatric airways are easily compressed by enlarged lymph nodes, detection of radiographic airway compression might be an objective criterion for diagnosing pulmonary tuberculosis.

Objective

To investigate the frequency and inter-observer agreement of airway compression on chest radiographs in children with pulmonary tuberculosis compared to those with a different lower respiratory tract infection.

Materials and methods

Chest radiographs of children with suspected pulmonary tuberculosis were read by two readers according to a standardised format and a third reader when there was disagreement. Radiographs of children with proven pulmonary tuberculosis were compared to those with a different lower respiratory tract infection. We evaluated frequency and location of radiographic airway compression. Findings were correlated with human immunodeficiency virus (HIV) status and age. We assessed inter-observer agreement using kappa statistics.

Results

We reviewed radiographs of 505 children (median age 25.9 months, interquartile range [IQR] 14.3–62.2). Radiographic airway compression occurred in 54/188 (28.7%) children with proven pulmonary tuberculosis and in 24/317 (7.6%) children with other types of lower respiratory tract infection (odds ratio [OR] 4.9; 95% confidence interval [CI] 2.9–8.3). A higher frequency of radiographic airway compression occurred in infants (22/101, or 21.8%) compared to older children (56/404, or 13.9%; OR 1.7; 95% CI 1.0–3.0). We found no association between airway compression and HIV infection. Inter-observer agreement ranged from none to fair (kappa of 0.0–0.4).

Conclusion

There is a strong association between airway compression on chest radiographs and confirmed pulmonary tuberculosis. However this finding's clinical use as an objective criterion for diagnosis of pulmonary tuberculosis in children is limited by poor inter-observer agreement.

http://ift.tt/2seEWIy

Assessment of airway compression on chest radiographs in children with pulmonary tuberculosis

Abstract

Background

Because small, pliable paediatric airways are easily compressed by enlarged lymph nodes, detection of radiographic airway compression might be an objective criterion for diagnosing pulmonary tuberculosis.

Objective

To investigate the frequency and inter-observer agreement of airway compression on chest radiographs in children with pulmonary tuberculosis compared to those with a different lower respiratory tract infection.

Materials and methods

Chest radiographs of children with suspected pulmonary tuberculosis were read by two readers according to a standardised format and a third reader when there was disagreement. Radiographs of children with proven pulmonary tuberculosis were compared to those with a different lower respiratory tract infection. We evaluated frequency and location of radiographic airway compression. Findings were correlated with human immunodeficiency virus (HIV) status and age. We assessed inter-observer agreement using kappa statistics.

Results

We reviewed radiographs of 505 children (median age 25.9 months, interquartile range [IQR] 14.3–62.2). Radiographic airway compression occurred in 54/188 (28.7%) children with proven pulmonary tuberculosis and in 24/317 (7.6%) children with other types of lower respiratory tract infection (odds ratio [OR] 4.9; 95% confidence interval [CI] 2.9–8.3). A higher frequency of radiographic airway compression occurred in infants (22/101, or 21.8%) compared to older children (56/404, or 13.9%; OR 1.7; 95% CI 1.0–3.0). We found no association between airway compression and HIV infection. Inter-observer agreement ranged from none to fair (kappa of 0.0–0.4).

Conclusion

There is a strong association between airway compression on chest radiographs and confirmed pulmonary tuberculosis. However this finding's clinical use as an objective criterion for diagnosis of pulmonary tuberculosis in children is limited by poor inter-observer agreement.

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Improving efficacy and efficiency through the implementation of a new organisational model in a Radiation Oncology Department

Abstract

Background

To evaluate a new organisational model, "process management" (PM), implemented in the Hospital Universitario Virgen de la Victoria (HUVV) compared with traditional models used in other Radiation Oncology Departments (RODs), in terms of efficacy and efficiency.

Methods

The study period ranged from September 2011 to August 2012. Efficacy was assessed, comparing the number of patients attended in first consultation and treated per month, average waiting time from referral to first visit and average waiting time from first visit to treatment. Data were collected from two public hospitals in Andalusia: the HUVV and another Public Hospital in Andalusia (PHA1). Efficiency was assessed comparing the costs per patient attended in first visit and treated at HUVV in 2012 compared with those of a second Public Hospital in Andalusia (PHA2) for 2008. The number of sessions saved using hypofractionation versus classical schemes during the year 2012 in HUVV was estimated, and the money saved was calculated.

Results

In the efficacy analysis, we found significant differences in the average waiting time for first visit, start of treatment, and the number of patients seen and treated annually. After calculating the total cost generated in the ROD, the efficiency analysis showed a lower cost per patient attended in first visit (EUR 599.17) and per patient treated (EUR 783.50), with a saving of 6035 sessions using hypofractionated schemes.

Conclusions

Process management in an ROD reduces time, both to first medical visit and to treatment initiation, allowing an optimisation of linear accelerator (LINAC) capacity.

http://ift.tt/2qv7Dke

Improving efficacy and efficiency through the implementation of a new organisational model in a Radiation Oncology Department

Abstract

Background

To evaluate a new organisational model, "process management" (PM), implemented in the Hospital Universitario Virgen de la Victoria (HUVV) compared with traditional models used in other Radiation Oncology Departments (RODs), in terms of efficacy and efficiency.

Methods

The study period ranged from September 2011 to August 2012. Efficacy was assessed, comparing the number of patients attended in first consultation and treated per month, average waiting time from referral to first visit and average waiting time from first visit to treatment. Data were collected from two public hospitals in Andalusia: the HUVV and another Public Hospital in Andalusia (PHA1). Efficiency was assessed comparing the costs per patient attended in first visit and treated at HUVV in 2012 compared with those of a second Public Hospital in Andalusia (PHA2) for 2008. The number of sessions saved using hypofractionation versus classical schemes during the year 2012 in HUVV was estimated, and the money saved was calculated.

Results

In the efficacy analysis, we found significant differences in the average waiting time for first visit, start of treatment, and the number of patients seen and treated annually. After calculating the total cost generated in the ROD, the efficiency analysis showed a lower cost per patient attended in first visit (EUR 599.17) and per patient treated (EUR 783.50), with a saving of 6035 sessions using hypofractionated schemes.

Conclusions

Process management in an ROD reduces time, both to first medical visit and to treatment initiation, allowing an optimisation of linear accelerator (LINAC) capacity.

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Improving efficacy and efficiency through the implementation of a new organisational model in a Radiation Oncology Department

Abstract

Background

To evaluate a new organisational model, "process management" (PM), implemented in the Hospital Universitario Virgen de la Victoria (HUVV) compared with traditional models used in other Radiation Oncology Departments (RODs), in terms of efficacy and efficiency.

Methods

The study period ranged from September 2011 to August 2012. Efficacy was assessed, comparing the number of patients attended in first consultation and treated per month, average waiting time from referral to first visit and average waiting time from first visit to treatment. Data were collected from two public hospitals in Andalusia: the HUVV and another Public Hospital in Andalusia (PHA1). Efficiency was assessed comparing the costs per patient attended in first visit and treated at HUVV in 2012 compared with those of a second Public Hospital in Andalusia (PHA2) for 2008. The number of sessions saved using hypofractionation versus classical schemes during the year 2012 in HUVV was estimated, and the money saved was calculated.

Results

In the efficacy analysis, we found significant differences in the average waiting time for first visit, start of treatment, and the number of patients seen and treated annually. After calculating the total cost generated in the ROD, the efficiency analysis showed a lower cost per patient attended in first visit (EUR 599.17) and per patient treated (EUR 783.50), with a saving of 6035 sessions using hypofractionated schemes.

Conclusions

Process management in an ROD reduces time, both to first medical visit and to treatment initiation, allowing an optimisation of linear accelerator (LINAC) capacity.

http://ift.tt/2qv7Dke

Improving efficacy and efficiency through the implementation of a new organisational model in a Radiation Oncology Department

Abstract

Background

To evaluate a new organisational model, "process management" (PM), implemented in the Hospital Universitario Virgen de la Victoria (HUVV) compared with traditional models used in other Radiation Oncology Departments (RODs), in terms of efficacy and efficiency.

Methods

The study period ranged from September 2011 to August 2012. Efficacy was assessed, comparing the number of patients attended in first consultation and treated per month, average waiting time from referral to first visit and average waiting time from first visit to treatment. Data were collected from two public hospitals in Andalusia: the HUVV and another Public Hospital in Andalusia (PHA1). Efficiency was assessed comparing the costs per patient attended in first visit and treated at HUVV in 2012 compared with those of a second Public Hospital in Andalusia (PHA2) for 2008. The number of sessions saved using hypofractionation versus classical schemes during the year 2012 in HUVV was estimated, and the money saved was calculated.

Results

In the efficacy analysis, we found significant differences in the average waiting time for first visit, start of treatment, and the number of patients seen and treated annually. After calculating the total cost generated in the ROD, the efficiency analysis showed a lower cost per patient attended in first visit (EUR 599.17) and per patient treated (EUR 783.50), with a saving of 6035 sessions using hypofractionated schemes.

Conclusions

Process management in an ROD reduces time, both to first medical visit and to treatment initiation, allowing an optimisation of linear accelerator (LINAC) capacity.

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In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells

Abstract

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34⁺ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10⁸ pDC can be produced from a typical cord blood unit. Blocking the aryl hydrocarbon receptor (AHR) pathway significantly increased the yield of pDC. When compared to pDC isolated from peripheral blood, in vitro differentiated pDC (ivD-pDC) exhibited an increased capacity to induce NK cell-mediated killing of ALL. Although ivD-pDC produced lower amounts of IFN-α than peripheral blood pDC upon TLR activation, they produced more IFN-λ2, known to play a critical role in the induction of anti-tumoral NK cell functions. Both TLR-9 and TLR-7 ligands triggered pDC-induced NK cell activation, offering the possibility to use any clinical-grade TLR-7 or TLR-9 ligands in future clinical trials. Finally, adoptive transfer of ivD-pDC cultured in the presence of an AHR antagonist cured humanized mice with minimal ALL disease. Collectively, our results pave the way to clinical-grade production of sufficient numbers of human pDC for innate immunotherapy against ALL and other refractory malignancies.

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via IFTTT

In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells

Abstract

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34⁺ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10⁸ pDC can be produced from a typical cord blood unit. Blocking the aryl hydrocarbon receptor (AHR) pathway significantly increased the yield of pDC. When compared to pDC isolated from peripheral blood, in vitro differentiated pDC (ivD-pDC) exhibited an increased capacity to induce NK cell-mediated killing of ALL. Although ivD-pDC produced lower amounts of IFN-α than peripheral blood pDC upon TLR activation, they produced more IFN-λ2, known to play a critical role in the induction of anti-tumoral NK cell functions. Both TLR-9 and TLR-7 ligands triggered pDC-induced NK cell activation, offering the possibility to use any clinical-grade TLR-7 or TLR-9 ligands in future clinical trials. Finally, adoptive transfer of ivD-pDC cultured in the presence of an AHR antagonist cured humanized mice with minimal ALL disease. Collectively, our results pave the way to clinical-grade production of sufficient numbers of human pDC for innate immunotherapy against ALL and other refractory malignancies.

http://ift.tt/2rOmVV5

Clinicopathological features and pathological evaluation of preoperative treatment of patients with resectable esophageal carcinosarcoma

Abstract

Background

Because esophageal carcinosarcoma (ECS) is rare, a treatment strategy similar to that employed in esophageal cancer is usually applied. However, the clinicopathological features and the treatment effects of preoperative chemotherapy or chemoradiotherapy (CT/CRT) are not well known.

Methods

We retrospectively evaluated clinical and pathological characteristics of consecutive patients with pathologically confirmed ECS who underwent esophagectomy from 1996 to 2011 in our institution, and assessed their pathological response to preoperative CT/CRT in surgically resected specimens.

Results

We identified 19 patients with a final diagnosis of ECS who had then undergone curative surgery. In 6 of these, the preoperative pathological diagnosis by biopsy had been squamous cell carcinoma. In 7 of 13 patients treated by surgery alone, clinical T factors were overdiagnosed compared with pathological findings. Of patients who received preoperative CT (5-fluorouracil plus cisplatin) with (n = 2) and without (n = 4) concurrent RT (41.4–50.4 Gy), two had a partial response, in three, the disease remained stable, and one patient had progressive disease. Histopathological evaluation showed a limited pathological response in the sarcomatous component. Median overall survival of patients with and without preoperative treatment was 28.0 and 47.2 months, respectively [HR = 1.55 (95% CI 0.36–6.56)], and median relapse free survival was 13.4 months versus not achieved [HR = 2.06 (95% CI 0.54–7.76)].

Conclusion

The problems associated with clinical T stage diagnosis as well as the lack of evidence for an effect of preoperative treatment, especially on the sarcomatous component, mean that treatment strategies for ECS should be considered with care.

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Clinicopathological features and pathological evaluation of preoperative treatment of patients with resectable esophageal carcinosarcoma

Abstract

Background

Because esophageal carcinosarcoma (ECS) is rare, a treatment strategy similar to that employed in esophageal cancer is usually applied. However, the clinicopathological features and the treatment effects of preoperative chemotherapy or chemoradiotherapy (CT/CRT) are not well known.

Methods

We retrospectively evaluated clinical and pathological characteristics of consecutive patients with pathologically confirmed ECS who underwent esophagectomy from 1996 to 2011 in our institution, and assessed their pathological response to preoperative CT/CRT in surgically resected specimens.

Results

We identified 19 patients with a final diagnosis of ECS who had then undergone curative surgery. In 6 of these, the preoperative pathological diagnosis by biopsy had been squamous cell carcinoma. In 7 of 13 patients treated by surgery alone, clinical T factors were overdiagnosed compared with pathological findings. Of patients who received preoperative CT (5-fluorouracil plus cisplatin) with (n = 2) and without (n = 4) concurrent RT (41.4–50.4 Gy), two had a partial response, in three, the disease remained stable, and one patient had progressive disease. Histopathological evaluation showed a limited pathological response in the sarcomatous component. Median overall survival of patients with and without preoperative treatment was 28.0 and 47.2 months, respectively [HR = 1.55 (95% CI 0.36–6.56)], and median relapse free survival was 13.4 months versus not achieved [HR = 2.06 (95% CI 0.54–7.76)].

Conclusion

The problems associated with clinical T stage diagnosis as well as the lack of evidence for an effect of preoperative treatment, especially on the sarcomatous component, mean that treatment strategies for ECS should be considered with care.

http://ift.tt/2qzwx16

Professor Enrico Mihich, 1928–2016

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Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4⁺ and CD8⁺, FOXP3⁺CD25^bright Treg, and "innate-like" CD56⁺) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4⁺ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4⁺ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4⁺ and CD8⁺ T cell subsets associated with higher frequencies of IFNγ⁺ and GrzB⁺ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

from Cancer via ola Kala on Inoreader http://ift.tt/2rOq6vY
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In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells

Abstract

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34⁺ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10⁸ pDC can be produced from a typical cord blood unit. Blocking the aryl hydrocarbon receptor (AHR) pathway significantly increased the yield of pDC. When compared to pDC isolated from peripheral blood, in vitro differentiated pDC (ivD-pDC) exhibited an increased capacity to induce NK cell-mediated killing of ALL. Although ivD-pDC produced lower amounts of IFN-α than peripheral blood pDC upon TLR activation, they produced more IFN-λ2, known to play a critical role in the induction of anti-tumoral NK cell functions. Both TLR-9 and TLR-7 ligands triggered pDC-induced NK cell activation, offering the possibility to use any clinical-grade TLR-7 or TLR-9 ligands in future clinical trials. Finally, adoptive transfer of ivD-pDC cultured in the presence of an AHR antagonist cured humanized mice with minimal ALL disease. Collectively, our results pave the way to clinical-grade production of sufficient numbers of human pDC for innate immunotherapy against ALL and other refractory malignancies.

from Cancer via ola Kala on Inoreader http://ift.tt/2rOmVV5
via IFTTT

Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4⁺ and CD8⁺, FOXP3⁺CD25^bright Treg, and "innate-like" CD56⁺) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4⁺ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4⁺ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4⁺ and CD8⁺ T cell subsets associated with higher frequencies of IFNγ⁺ and GrzB⁺ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

from Cancer via ola Kala on Inoreader http://ift.tt/2rOq6vY
via IFTTT

Professor Enrico Mihich, 1928–2016

from Cancer via ola Kala on Inoreader http://ift.tt/2rd78wm
via IFTTT

In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells

Abstract

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34⁺ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10⁸ pDC can be produced from a typical cord blood unit. Blocking the aryl hydrocarbon receptor (AHR) pathway significantly increased the yield of pDC. When compared to pDC isolated from peripheral blood, in vitro differentiated pDC (ivD-pDC) exhibited an increased capacity to induce NK cell-mediated killing of ALL. Although ivD-pDC produced lower amounts of IFN-α than peripheral blood pDC upon TLR activation, they produced more IFN-λ2, known to play a critical role in the induction of anti-tumoral NK cell functions. Both TLR-9 and TLR-7 ligands triggered pDC-induced NK cell activation, offering the possibility to use any clinical-grade TLR-7 or TLR-9 ligands in future clinical trials. Finally, adoptive transfer of ivD-pDC cultured in the presence of an AHR antagonist cured humanized mice with minimal ALL disease. Collectively, our results pave the way to clinical-grade production of sufficient numbers of human pDC for innate immunotherapy against ALL and other refractory malignancies.

http://ift.tt/2rOmVV5

Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4⁺ and CD8⁺, FOXP3⁺CD25^bright Treg, and "innate-like" CD56⁺) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4⁺ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4⁺ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4⁺ and CD8⁺ T cell subsets associated with higher frequencies of IFNγ⁺ and GrzB⁺ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

http://ift.tt/2rOq6vY

Professor Enrico Mihich, 1928–2016

http://ift.tt/2rd78wm

Rapid Cataract Progression after Nd:YAG Vitreolysis for Vitreous Floaters: A Case Report and Literature Review

Purpose: We report a case of rapid cataract progression after Nd:YAG vitreolysis for vitreous floaters. Case Report: A 55-year-old man presented with acute onset of blurred vision following Nd:YAG vitreolysis for symptomatic floaters in the left eye. His initial best corrected visual acuity (BCVA) was 20/1,000 in the left eye. Ocular examinations showed frost-like opacities of the lens and a suspected break of the posterior capsule in the left eye. There were no detectable retinal lesions. Cataract surgery was then arranged. Posterior capsular rupture and vitreous loss occurred during surgery, which required a subsequent pars plana vitrectomy. After the surgery, BCVA in the left eye gradually improved to 20/20 and was maintained during a 1-year follow-up period. Conclusion: Crystalline lens injuries and rapid cataract progression may occur following Nd:YAG vitreolysis. While dealing with this type of complicated cataract, clinicians should be aware of the possibility of posterior lens capsule rupture during surgery and the need for combined vitrectomy.
Case Rep Ophthalmol 2017;8:321–325

http://ift.tt/2quCPjC

Spironolactone as an Adjunctive Treatment in Neovascular Age-Related Macular Degeneration

Neovascular age-related macular degeneration (AMD) is a potentially sight-threatening condition. The current standard-of-care treatment regimen is serial intravitreal antivascular endothelial growth factor injections. While these typically have great success, they do carry exceptional treatment burden on the patient, cost burden due to their required frequency of use, and the risk of endophthalmitis, which can be devastating. This case report explores an alternative potential option as a treatment adjunct for neovascular AMD (nAMD), and identifies some of the overlap between nAMD and central serous chorioretionpathy. Future research is needed to better understand the role of mineralocorticoid receptor antagonist treatment in this disease spectrum.
Case Rep Ophthalmol 2017;8:314–320

http://ift.tt/2rOAxzx

Multiquadrant Subtenon Triamcinolone Injection for Acute Corneal Graft Rejection: A Case Report

Background: We report a case of reversal of an acute corneal graft rejection following multiquadrant subtenon triamcinolone injection. Case Presentation: A 19-year-old woman who had acute corneal graft rejection failed to show resolution of the graft rejection after standard treatment with systemic, intravenous, and topical steroids. The graft rejection, however, responded to injection of triamcinolone in multiple subtenon quadrants. Conclusions: For corneal graft rejection, multiquadrant subtenon triamcinolone injections may be a safe adjunct to systemic treatment.
Case Rep Ophthalmol 2017;8:308–313

http://ift.tt/2quVbAX

A Case of Childhood-Onset Giant Cell Tumor that Caused Optic Nerve Atrophy in Both Eyes

Purpose: The purpose of this study was to report the case of a female patient who had a giant cell tumor in the paranasal sinus during childhood, and while undergoing multiple resection surgeries experienced optic atrophy in both eyes. Case Presentation: This study involved a 35-year-old woman who was previously diagnosed with a giant cell tumor of the paranasal sinus bone at age 13. A CT scan revealed a large tumor extending from the sphenoid sinus to the ethmoid sinus. At age 14, a tumor resection was performed in conjunction with radiation therapy. However, after resection and radiation therapy there were repeated recurrences, and additional resections were performed. Ophthalmically, there was marked optical atrophy in both eyes, and Goldmann visual field perimetry revealed that only the arcuate peripheral area remained on the nasal side of the right eye, and that there were dark spots in the paracentral area of the left eye. Conclusions: In this case, a large giant cell tumor occurred in the sphenoid sinus and ethmoid sinus during childhood, and it is thought that optic atrophy was caused by compressive optic neuropathy. The sphenoid sinus and ethmoid sinuses are anatomically close to the optic nerve, and when a tumor grows larger at this site it can easily put pressure on the optic nerve. Therefore, early detection and treatment are important.
Case Rep Ophthalmol 2017;8:301–307

http://ift.tt/2rOJed3

Professor Enrico Mihich, 1928–2016

http://ift.tt/2rd78wm

Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4⁺ and CD8⁺, FOXP3⁺CD25^bright Treg, and "innate-like" CD56⁺) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4⁺ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4⁺ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4⁺ and CD8⁺ T cell subsets associated with higher frequencies of IFNγ⁺ and GrzB⁺ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

http://ift.tt/2rOq6vY

Professor Enrico Mihich, 1928–2016

from Cancer via ola Kala on Inoreader http://ift.tt/2rd78wm
via IFTTT

Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4⁺ and CD8⁺, FOXP3⁺CD25^bright Treg, and "innate-like" CD56⁺) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4⁺ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4⁺ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4⁺ and CD8⁺ T cell subsets associated with higher frequencies of IFNγ⁺ and GrzB⁺ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

from Cancer via ola Kala on Inoreader http://ift.tt/2rOq6vY
via IFTTT

Improving the utility of 1 H-MRS for the differentiation of glioma recurrence from radiation necrosis

Abstract

Proton magnetic resonance spectroscopy (¹H-MRS) has shown promise in distinguishing recurrent high-grade glioma from posttreatment radiation effect (PTRE). The purpose of this study was to establish objective ¹H-MRS criteria based on metabolite peak height ratios to distinguish recurrent tumor (RT) from PTRE. A retrospective analysis of magnetic resonance imaging and ¹H-MRS data was performed. Spectral metabolites analyzed included N-acetylaspartate, choline (Cho), creatine (Cr), lactate (Lac), and lipids (Lip). Quantitative ¹H-MRS criteria to differentiate RT from PTRE were identified using 81 biopsy-matched spectral voxels. A receiver operating characteristic curve analysis was conducted for all metabolite ratio combinations with the pathology diagnosis as the classification variable. Forward discriminant analysis was used to identify ratio variables that maximized the correct classification of RT versus PTRE. Our results were applied to 205 records without biopsy-matched voxels to examine the percent agreement between our criteria and the radiologic diagnoses. Five ratios achieved an acceptable balance [area under the curve (AUC) ≥ 0.700] between sensitivity and specificity for distinguishing RT from PTRE, and each ratio defined a criterion for diagnosing RT. The ratios are as follows: Cho/Cr > 1.54 (sensitivity 66%, specificity 79%), Cr/Cho ≤ 0.63 (sensitivity 65%, specificity 79%), Lac/Cho ≤ 2.67 (sensitivity 85%, specificity 58%), Lac/Lip ≤ 1.64 (sensitivity 54%, specificity 95%), and Lip/Lac > 0.58 (sensitivity 56%, specificity 95%). Application of our ratio criteria in prospective studies may offer an alternative to biopsy or visual spectral pattern recognition to distinguish RT from PTRE in patients with gliomas.

http://ift.tt/2rOo2UI

Ischemic stroke and intracranial hemorrhage in patients with recurrent glioblastoma multiforme, treated with bevacizumab

Abstract

Bevacizumab (BVZ), a monoclonal antibody directed against vascular endothelial growth factor (VEGF), has been suspected to increase the incidence of ischemic stroke (IS) and intracranial hemorrhage (ICH) in GBM patients. Intracranial vascular events, such as IS and ICH, were retrospectively analyzed in 364 MRI scans of 82 patients with recurrent GBM (1st/2nd/3rd relapse). Out of these 82 patients, 40 were treated with BVZ (178 scans) in addition to basic treatment, whereas 42 patients matching for age and gender received basic treatment (186 scans). Distribution of typical vascular risk factors between both groups was analyzed retrospectively. In seven out of 82 patients (8%) vascular events were detected in MRI. Four vascular events were recorded in the BVZ-group (3 IS and 1 ICH), and 3 vascular events were found in the Control-group (1 IS and 2 ICH; p > 0.05 between both groups). Likewise, vascular risk factors (arterial hypertension, diabetes mellitus, obesity, former vascular event, hyperlipidemia, tobacco consumption and/or hypercholesterolemia) did not differ significantly between both groups. BVZ treatment does not seem to be associated with an increased risk for vascular events in patients with GBM in recurrence.

http://ift.tt/2quWG24

Ethical considerations of neuro-oncology trial design in the era of precision medicine

Abstract

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

http://ift.tt/2sebuSY