Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung

Abstract

Background

There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma.

Methods

Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis.

Results

Twenty-two patients have small cell carcinoma, and 5 patients have large cell neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after the first visit (p < 0.01) and undergo lobectomy (p < 0.01) and whose pro-gastrin-releasing peptide ≦ 72 pg/ml (p = 0.04) performed good prognosis after surgery. In multivariate analysis, surgery within 60 days and operative procedure were independent factors associated with OS.

Conclusion

Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung should be performed as early as possible, and better outcome can be obtained with lobectomy than partial resection.

http://ift.tt/2sBRcYF

Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung

Abstract

Background

There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma.

Methods

Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis.

Results

Twenty-two patients have small cell carcinoma, and 5 patients have large cell neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after the first visit (p < 0.01) and undergo lobectomy (p < 0.01) and whose pro-gastrin-releasing peptide ≦ 72 pg/ml (p = 0.04) performed good prognosis after surgery. In multivariate analysis, surgery within 60 days and operative procedure were independent factors associated with OS.

Conclusion

Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung should be performed as early as possible, and better outcome can be obtained with lobectomy than partial resection.

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Quality of partner support moderates positive affect in cancer patients

Abstract

Objective

In the present study we examined whether four support quality-related characteristics moderate the impact of received partner support on cancer patients' positive affect. The support quality-related characteristics were: patients' perception regarding the willingness of their partners to offer support, patients' perception that partner support is certain, patients' satisfaction with partner relationship and overall patients' satisfaction with partner support.

Method

Seventy seven recently diagnosed cancer patients were assessed at two time points, during chemotherapy treatment (baseline) and seven months later (follow-up). Two types of received support were examined, emotional support and advice-guidance from partner. Multiple regression analyses were performed to determine the moderating effect of the quality-related variables on the relationship between received support at baseline and patient positive affect at seven-month follow-up.

Results

Results showed that all four quality-related characteristics had a moderating role (f² ranged between .06 and .16, p < .05). Emotional support predicted positive affect only when patients reported high partner willingness to offer support, considered the partner support certain, were satisfied with the partner relationship (a trend), and were satisfied with the received support. In contrast, when patients perceived their partners as unwilling to provide support and were dissatisfied with the relationship, support (both emotional and advice-guidance and advice-guidance, respectively) exhibited a negative impact on positive affect.

Conclusions

The findings suggest that only when the quality of support is high, does social support have a positive impact on patients' positive affect.

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Quality of partner support moderates positive affect in cancer patients

Abstract

Objective

In the present study we examined whether four support quality-related characteristics moderate the impact of received partner support on cancer patients' positive affect. The support quality-related characteristics were: patients' perception regarding the willingness of their partners to offer support, patients' perception that partner support is certain, patients' satisfaction with partner relationship and overall patients' satisfaction with partner support.

Method

Seventy seven recently diagnosed cancer patients were assessed at two time points, during chemotherapy treatment (baseline) and seven months later (follow-up). Two types of received support were examined, emotional support and advice-guidance from partner. Multiple regression analyses were performed to determine the moderating effect of the quality-related variables on the relationship between received support at baseline and patient positive affect at seven-month follow-up.

Results

Results showed that all four quality-related characteristics had a moderating role (f² ranged between .06 and .16, p < .05). Emotional support predicted positive affect only when patients reported high partner willingness to offer support, considered the partner support certain, were satisfied with the partner relationship (a trend), and were satisfied with the received support. In contrast, when patients perceived their partners as unwilling to provide support and were dissatisfied with the relationship, support (both emotional and advice-guidance and advice-guidance, respectively) exhibited a negative impact on positive affect.

Conclusions

The findings suggest that only when the quality of support is high, does social support have a positive impact on patients' positive affect.

http://ift.tt/2ByWV4j

Ketamine induces apoptosis in lung adenocarcinoma cells by regulating the expression of CD69

Abstract

Ketamine, an anesthetic, analgesic, or sedative, is widely used for the treatment of cancer pain. Recently, ketamine has been also reported to be tumor repressor for inhibiting proliferation, invasion, and migration, and inducing apoptosis in many cancers. However, whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. A LUAD cell line A549 was incubated with ketamine at 0, 1, 10, and 100 μmol/L for 24 h. Trypan blue staining was used to detect the cell viability. Flow cytometry (FACS) was applied to evaluate cell apoptosis proportion. The expression of CD69 was quantitated by western blotting. Ketamine induced the A549 cell apoptosis in a concentration-dependent manner. CD69 was downregulated in LUAD patients' cancer tissue compared with the normal tissue. CD69 can be upregulated in ketamine treating A549 cells and induce the A549 cell apoptosis. Rescue experiment showed that downregulation of CD69 significantly blocked the function of ketamine on inducing apoptosis. Taken together, our results demonstrated that ketamine induced LUAD cells apoptosis by upregulating the CD69 expression. This study suggests that the ketamine can be potential drug for LUAD treatment, and the ketamine/CD69 signaling may be the new potential therapeutic target LUAD therapy.

Whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. Our study in A549 demonstrated that ketamine induced LUAD cells apoptosis by upregulating the CD69 expression. This study suggests that the ketamine can be potential drug for LUAD treatment, and the ketamine/CD69 signaling may be the new potential therapeutic target LUAD therapy.

http://ift.tt/2EMKK5T

Ketamine induces apoptosis in lung adenocarcinoma cells by regulating the expression of CD69

Abstract

Ketamine, an anesthetic, analgesic, or sedative, is widely used for the treatment of cancer pain. Recently, ketamine has been also reported to be tumor repressor for inhibiting proliferation, invasion, and migration, and inducing apoptosis in many cancers. However, whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. A LUAD cell line A549 was incubated with ketamine at 0, 1, 10, and 100 μmol/L for 24 h. Trypan blue staining was used to detect the cell viability. Flow cytometry (FACS) was applied to evaluate cell apoptosis proportion. The expression of CD69 was quantitated by western blotting. Ketamine induced the A549 cell apoptosis in a concentration-dependent manner. CD69 was downregulated in LUAD patients' cancer tissue compared with the normal tissue. CD69 can be upregulated in ketamine treating A549 cells and induce the A549 cell apoptosis. Rescue experiment showed that downregulation of CD69 significantly blocked the function of ketamine on inducing apoptosis. Taken together, our results demonstrated that ketamine induced LUAD cells apoptosis by upregulating the CD69 expression. This study suggests that the ketamine can be potential drug for LUAD treatment, and the ketamine/CD69 signaling may be the new potential therapeutic target LUAD therapy.

Whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. Our study in A549 demonstrated that ketamine induced LUAD cells apoptosis by upregulating the CD69 expression. This study suggests that the ketamine can be potential drug for LUAD treatment, and the ketamine/CD69 signaling may be the new potential therapeutic target LUAD therapy.

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The brigatinib experience: a new generation of therapy for ALK-positive non-small-cell lung cancer

Future Oncology, Ahead of Print.


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The brigatinib experience: a new generation of therapy for ALK-positive non-small-cell lung cancer

Future Oncology, Ahead of Print.


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Post-Cardiac Arrest Management: Time to Cool It on Cooling?

No abstract available

http://ift.tt/2o4NMsD

Targeted Temperature Management After Cardiac Arrest: Systematic Review and Meta-analyses

BACKGROUND: Targeted temperature management (TTM) with therapeutic hypothermia is an integral component of postarrest care for survivors. However, recent randomized controlled trials (RCTs) have failed to demonstrate the benefit of TTM on clinical outcomes. We sought to determine if the pooled data from available RCTs support the use of prehospital and/or in-hospital TTM after cardiac arrest. METHODS: A comprehensive search of SCOPUS, Elsevier's abstract and citation database of peer-reviewed literature, from 1966 to November 2016 was performed using predefined criteria. Therapeutic hypothermia was defined as any strategy that aimed to cool post–cardiac arrest survivors to a temperature ≤34°C. Normothermia was temperature of ≥36°C. We compared mortality and neurologic outcomes in patients by categorizing the studies into 2 groups: (1) hypothermia versus normothermia and (2) prehospital hypothermia versus in-hospital hypothermia using standard meta-analytic methods. A random effects modeling was utilized to estimate comparative risk ratios (RR) and 95% confidence intervals (CIs). RESULTS: The hypothermia and normothermia strategies were compared in 5 RCTs with 1389 patients, whereas prehospital hypothermia and in-hospital hypothermia were compared in 6 RCTs with 3393 patients. We observed no difference in mortality (RR, 0.88; 95% CI, 0.73–1.05) or neurologic outcomes (RR, 1.26; 95% CI, 0.92–1.72) between the hypothermia and normothermia strategies. Similarly, no difference was observed in mortality (RR, 1.00; 95% CI, 0.97–1.03) or neurologic outcome (RR, 0.96; 95% CI, 0.85–1.08) between the prehospital hypothermia versus in-hospital hypothermia strategies. CONCLUSIONS: Our results suggest that TTM with therapeutic hypothermia may not improve mortality or neurologic outcomes in postarrest survivors. Using therapeutic hypothermia as a standard of care strategy of postarrest care in survivors may need to be reevaluated.

http://ift.tt/2o2mXpi

Perioperative Cardiac Arrest: Focus on Malignant Hyperthermia (MH)

No abstract available

http://ift.tt/2odiwXN

Perioperative Cardiac Arrest: Focus on Local Anesthetic Systemic Toxicity (LAST)

No abstract available

http://ift.tt/2o5nN4D

Perioperative Cardiac Arrest: Focus on Anaphylaxis

No abstract available

http://ift.tt/2obsSaP

Cancers, Vol. 10, Pages 53: A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas

Cancers, Vol. 10, Pages 53: A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas

Cancers doi: 10.3390/cancers10020053

Authors: Varun Monga Umang Swami Munir Tanas Aaron Bossler Sarah L. Mott Brian J. Smith Mohammed Milhem

Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical trials, but most of the findings have not supported its use. We hypothesized the existence of an epigenetically mediated "angiogenic switch", and the tumor microenvironment, prevents bevacizumab from truly blocking angiogenesis. The addition of valproic acid (VPA), a weak histone deacetylase inhibitor, and bevacizumab, a monoclonal antibody against vascular endothelial growth factor, together with the cytotoxic effects of gemcitabine and docetaxel, may enhance responses and alter chemoresistance. This was designed as a phase I/II trial with primary endpoints including safety of the treatment combination and tumor response. Unresectable or metastatic sarcoma patients &gt;18 years of age, irrespective of number of prior treatments, received VPA 40 mg/kg orally for 5 days prior to day 1, bevacizumab at 15 mg/kg IV on day 1, gemcitabine 900 mg/m2 (day 1, day 8), and docetaxel 75 mg/m2 (day 8). Cycles were of 28 day duration. Bevacizumab and VPA were continued as maintenance after 6 cycles, until disease progression. A standard 3 + 3 phase I dose de-escalation design was utilized to evaluate safety. Gain of function p53 gene mutation testing was performed on available archival tissue specimens. A total of 46 patients (30 female, 16 male) with median age of 60 (range 24–81) years were enrolled; 34 (73.9%) patients received prior chemotherapy, 14 (30%) of which received prior gemcitabine and docetaxel. Patients received a median of 5.5 cycles (range 0–24 of treatment (min 0, one patient died prior to completing the first cycle; max: 24, one patient received 6 cycles and 18 maintenance cycles before progressing). Seventeen patients underwent dose reduction, of which VPA was reduced in 6 patients. Forty-one patients were evaluable for response. There was a confirmed complete response in 1 (epithelioid sarcoma), and a partial response (PR) in 6 (1 carcinosarcoma, 2 extrauterine leiomyosarcoma (LMS), 2 undifferentiated pleomorphic sarcoma, and 1 uterine LMS) patients. Stable disease (SD) was seen in 21 patients for at least 2 months. One subject with prior gemcitabine and docetaxel had PR, and 7 had SD. Median progression-free survival (PFS) was 5.7 months (95% CI: 2.1–8.0), and overall survival (OS) was 12.9 months (95% CI: 8.3–14.5). Three patients died due to tumor progression while on the study. The combination of VPA, bevacizumab, gemcitabine, and docetaxel appears to be moderately safe and well tolerated. Given that there are very limited options for patients with relapsed refractory STS, this drug combination may be an important therapy to consider. This combination treatment deserves further investigation in epithelioid and carcinosarcoma subtypes.

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Cardiac Arrest in the Operating Room: Part 2—Special Situations in the Perioperative Period

As noted in part 1 of this series, periprocedural cardiac arrest (PPCA) can differ greatly in etiology and treatment from what is described by the American Heart Association advanced cardiac life support algorithms, which were largely developed for use in out-of-hospital cardiac arrest and in-hospital cardiac arrest outside of the perioperative space. Specifically, there are several life-threatening causes of PPCA of which the management should be within the skill set of all anesthesiologists. However, previous research has demonstrated that continued review and training in the management of these scenarios is greatly needed and is also associated with improved delivery of care and outcomes during PPCA. There is a growing body of literature describing the incidence, causes, treatment, and outcomes of common causes of PPCA (eg, malignant hyperthermia, massive trauma, and local anesthetic systemic toxicity) and the need for a better awareness of these topics within the anesthesiology community at large. As noted in part 1 of this series, these events are always witnessed by a member of the perioperative team, frequently anticipated, and involve rescuer–providers with knowledge of the patient and the procedure they are undergoing or have had. Formulation of an appropriate differential diagnosis and rapid application of targeted interventions are critical for good patient outcome. Resuscitation algorithms that include the evaluation and management of common causes leading to cardiac in the perioperative setting are presented. Practicing anesthesiologists need a working knowledge of these algorithms to maximize good outcomes.

http://ift.tt/2o5nRBp

Cardiac Arrest in the Operating Room: Resuscitation and Management for the Anesthesiologist Part 1

Cardiac arrest in the operating room and procedural areas has a different spectrum of causes (ie, hypovolemia, gas embolism, and hyperkalemia), and rapid and appropriate evaluation and management of these causes require modification of traditional cardiac arrest algorithms. There is a small but growing body of literature describing the incidence, causes, treatments, and outcomes of circulatory crisis and perioperative cardiac arrest. These events are almost always witnessed, frequently known, and involve rescuer providers with knowledge of the patient and their procedure. In this setting, there can be formulation of a differential diagnosis and a directed intervention that treats the likely underlying cause(s) of the crisis while concurrently managing the crisis itself. Management of cardiac arrest of the perioperative patient is predicated on expert opinion, physiologic rationale, and an understanding of the context in which these events occur. Resuscitation algorithms should consider the evaluation and management of these causes of crisis in the perioperative setting.

http://ift.tt/2ocrCEj

Cancers, Vol. 10, Pages 53: A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas

Cancers, Vol. 10, Pages 53: A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas

Cancers doi: 10.3390/cancers10020053

Authors: Varun Monga Umang Swami Munir Tanas Aaron Bossler Sarah L. Mott Brian J. Smith Mohammed Milhem

Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical trials, but most of the findings have not supported its use. We hypothesized the existence of an epigenetically mediated "angiogenic switch", and the tumor microenvironment, prevents bevacizumab from truly blocking angiogenesis. The addition of valproic acid (VPA), a weak histone deacetylase inhibitor, and bevacizumab, a monoclonal antibody against vascular endothelial growth factor, together with the cytotoxic effects of gemcitabine and docetaxel, may enhance responses and alter chemoresistance. This was designed as a phase I/II trial with primary endpoints including safety of the treatment combination and tumor response. Unresectable or metastatic sarcoma patients &gt;18 years of age, irrespective of number of prior treatments, received VPA 40 mg/kg orally for 5 days prior to day 1, bevacizumab at 15 mg/kg IV on day 1, gemcitabine 900 mg/m2 (day 1, day 8), and docetaxel 75 mg/m2 (day 8). Cycles were of 28 day duration. Bevacizumab and VPA were continued as maintenance after 6 cycles, until disease progression. A standard 3 + 3 phase I dose de-escalation design was utilized to evaluate safety. Gain of function p53 gene mutation testing was performed on available archival tissue specimens. A total of 46 patients (30 female, 16 male) with median age of 60 (range 24–81) years were enrolled; 34 (73.9%) patients received prior chemotherapy, 14 (30%) of which received prior gemcitabine and docetaxel. Patients received a median of 5.5 cycles (range 0–24 of treatment (min 0, one patient died prior to completing the first cycle; max: 24, one patient received 6 cycles and 18 maintenance cycles before progressing). Seventeen patients underwent dose reduction, of which VPA was reduced in 6 patients. Forty-one patients were evaluable for response. There was a confirmed complete response in 1 (epithelioid sarcoma), and a partial response (PR) in 6 (1 carcinosarcoma, 2 extrauterine leiomyosarcoma (LMS), 2 undifferentiated pleomorphic sarcoma, and 1 uterine LMS) patients. Stable disease (SD) was seen in 21 patients for at least 2 months. One subject with prior gemcitabine and docetaxel had PR, and 7 had SD. Median progression-free survival (PFS) was 5.7 months (95% CI: 2.1–8.0), and overall survival (OS) was 12.9 months (95% CI: 8.3–14.5). Three patients died due to tumor progression while on the study. The combination of VPA, bevacizumab, gemcitabine, and docetaxel appears to be moderately safe and well tolerated. Given that there are very limited options for patients with relapsed refractory STS, this drug combination may be an important therapy to consider. This combination treatment deserves further investigation in epithelioid and carcinosarcoma subtypes.

http://ift.tt/2Hpmqpt

Lower pole approach in retroperitoneal laparoscopic radical nephrectomy: a new approach for the management of renal vascular pedicle

Abstract

Background

The objective of this study was to examine the effectiveness and safety of lower pole (LP) approach in retroperitoneal laparoscopic radical nephrectomy (LRN).

Methods

One hundred thirty-two renal cancer patients were scheduled for selective retroperitoneal LRN. The surgery parameters and outcomes were compared. Out of 132 patients, 78 (59.1%) patients underwent LRN via LP approach, while 54 (40.9%) patients underwent LRN via lateroposterior space (LPS) approach.

Results

Compared to LPS group, the LP group had a higher body mass index (27.0 ± 1.7 kg/m² vs. 24.5 ± 1.8 kg/m², P <  0.0001) and a larger tumor size (6.9 ± 3.5 cm vs. 4.1 ± 3.3 cm, P <  0.0001). The LP approach reduced the volumes of blood loss and transfusion significantly (135.3 ± 17.2 mL vs. 219.6 ± 30.9 mL, P <  0.0001; 55.6 ± 28.3 vs. 141.1 ± 50.4 mL, P <  0.0001) as compared to the LPS approach. The LP approach also decreased the risk of conversion to open procedure (1.3 vs. 7.4%, P <  0.05).

Conclusions

The LP approach is an effective and safe alternative to the LPS approach for retroperitoneal LRN and might be more suitable for patients with obesity, large tumors, tumors located at the medial part of the kidney, or renal pedicular adhesion.

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SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma

Abstract

Background

SH3-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor (GEF), was consider as a key signal that determines cancer cell invasion. Although SGEF has been considered to highly express in glioma and prostate cancer. However, it is not well illustrated in LAC.

Methods

In this experiment, expression of SGEF was detected in 92 LAC and corresponding normal tissue samples by immunohistochemistry. In addition, we evaluated the invasion and migration of lung adenocarcinoma cells by the gain and loss of SGEF expression. Furthermore, RhoG activity was measured by GST pull-down assay.

Results

SGEF is highly expressed in LAC tissues than in normal lung tissues and was associated with the TNM stage. Lung adenocarcinoma patients with low SGEF subgroup had longer overall survival compared to those with high expression. Furthermore, univariate analysis showed that SGEF expression was an independent prognostic factor for overall survival in lung adenocarcinoma. Silencing of SGEF effectively suppressed the invasion and migration of human lung adenocarcinoma cells in vitro by inhibiting RhoG activity, and over-expression of SGEF could reverse this phenomena.

Conclusion

SGEF is a novel prognostic target in human lung adenocarcinoma.

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Lower pole approach in retroperitoneal laparoscopic radical nephrectomy: a new approach for the management of renal vascular pedicle

Abstract

Background

The objective of this study was to examine the effectiveness and safety of lower pole (LP) approach in retroperitoneal laparoscopic radical nephrectomy (LRN).

Methods

One hundred thirty-two renal cancer patients were scheduled for selective retroperitoneal LRN. The surgery parameters and outcomes were compared. Out of 132 patients, 78 (59.1%) patients underwent LRN via LP approach, while 54 (40.9%) patients underwent LRN via lateroposterior space (LPS) approach.

Results

Compared to LPS group, the LP group had a higher body mass index (27.0 ± 1.7 kg/m² vs. 24.5 ± 1.8 kg/m², P <  0.0001) and a larger tumor size (6.9 ± 3.5 cm vs. 4.1 ± 3.3 cm, P <  0.0001). The LP approach reduced the volumes of blood loss and transfusion significantly (135.3 ± 17.2 mL vs. 219.6 ± 30.9 mL, P <  0.0001; 55.6 ± 28.3 vs. 141.1 ± 50.4 mL, P <  0.0001) as compared to the LPS approach. The LP approach also decreased the risk of conversion to open procedure (1.3 vs. 7.4%, P <  0.05).

Conclusions

The LP approach is an effective and safe alternative to the LPS approach for retroperitoneal LRN and might be more suitable for patients with obesity, large tumors, tumors located at the medial part of the kidney, or renal pedicular adhesion.

http://ift.tt/2o5bUeW

SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma

Abstract

Background

SH3-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor (GEF), was consider as a key signal that determines cancer cell invasion. Although SGEF has been considered to highly express in glioma and prostate cancer. However, it is not well illustrated in LAC.

Methods

In this experiment, expression of SGEF was detected in 92 LAC and corresponding normal tissue samples by immunohistochemistry. In addition, we evaluated the invasion and migration of lung adenocarcinoma cells by the gain and loss of SGEF expression. Furthermore, RhoG activity was measured by GST pull-down assay.

Results

SGEF is highly expressed in LAC tissues than in normal lung tissues and was associated with the TNM stage. Lung adenocarcinoma patients with low SGEF subgroup had longer overall survival compared to those with high expression. Furthermore, univariate analysis showed that SGEF expression was an independent prognostic factor for overall survival in lung adenocarcinoma. Silencing of SGEF effectively suppressed the invasion and migration of human lung adenocarcinoma cells in vitro by inhibiting RhoG activity, and over-expression of SGEF could reverse this phenomena.

Conclusion

SGEF is a novel prognostic target in human lung adenocarcinoma.

http://ift.tt/2obY8q1

A Randomized Multicenter Phase II Study of Docosahexaenoic Acid in Patients with a History of Breast Cancer, Premalignant Lesions or Benign Breast Disease

Obesity, a cause of subclinical inflammation, is a risk factor for the development of postmenopausal breast cancer (BC) and is associated with poorer cancer outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti-inflammatory properties. We hypothesized that treatment with DHA would reduce the expression of proinflammatory genes and aromatase, the rate-limiting enzyme for estrogen biosynthesis, in benign breast tissue of overweight/obese women. A randomized, placebo-controlled, double-blind phase II study of DHA given for 12 weeks to overweight/obese women with a history of stage I-III BC, DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried out. In this placebo controlled trial, the primary objective was to determine whether DHA (1000mg by mouth twice daily) reduced breast tissue levels of TNF-α. Secondary objectives included evaluation of the effect of DHA on breast tissue levels of COX-2, IL-1β, aromatase, white adipose tissue inflammation, and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to assess compliance. From July 2013 - November 2015, 64 participants were randomized and treated on trial (32 women per arm). Increased levels of omega-3 fatty acids in red blood cells were detected following treatment with DHA (P<0.001) but not placebo. Treatment with DHA did not alter levels of TNF-α (P=0.71), or other biomarkers including the transcriptome in breast samples. Treatment with DHA was overall well-tolerated. Although compliance was confirmed, we did not observe changes in the levels of prespecified biomarkers in the breast after treatment with DHA when compared to placebo.

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Distinct chemopreventive effects of aspirin in diffuse and intestinal-type gastric cancer

Introduction: Although aspirin/NSAIDs may have potential preventive effects on several cancers, it remains unclear on gastric cancer. The purpose of this study was to compare the risk of developing gastric cancer and the histological changes of intestinal metaplasia and neutrophil infiltration, between aspirin/NSAIDs users and non-users. Methods: Using an electronic endoscopy database in two hospitals from 1996 to 2017, we analyzed the data from patients with chronic gastritis who received aspirin or NSAIDs prior to upper gastrointestinal endoscopy. One-to-one propensity score matching was performed to compare the proportion of gastric cancer, intestinal metaplasia, and neutrophil infiltration between these drug users and non-users. Results: We analyzed 2082 aspirin users and 2082 non-users as well as 898 NSAIDs users and 898 non-users. Six diffuse-type and 19 intestinal-type gastric cancer, 1243 intestinal metaplasia, and 1503 neutrophil infiltration patients were identified. The proportion of diffuse-type gastric cancer (0.05%) was 80% lower in the aspirin-users compared with the non-users (0.24%), and there was no case of diffuse-type cancer in patients who take aspirin for more than 2 years. In contrast, intestinal-type gastric cancer incidence was significantly higher in the aspirin-users (0.72%) compared with the non-users (0.14%). No significant differences in the incidence of gastric cancer were found between NSAIDs use and non-users. NSAIDs use was significantly associated with decreased proportion of neutrophil infiltration compared with non-users. Conclusion: Aspirin may have distinct effects between intestinal-type and diffuse-type gastric cancer development.

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Asparagine Bioavailability Drives Breast Cancer Metastasis [Research Watch]

Asparagine depletion reduces breast cancer invasion and metastasis without affecting primary tumor growth.

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The PI3K{alpha} Inhibitor Alpelisib Has Activity in PIK3CA-altered Tumors [Research Watch]

The PI3Kα inhibitor alpelisib achieved a 58.2% disease control rate in PIK3CA-altered solid tumors.

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A Next-Generation Chimeric Antigen Receptor Induces JAK-STAT Signaling [Research Watch]

CAR-T cells designed to activate JAK–STAT signaling show enhanced persistence and antitumor activity.

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DNMT3A DNA-Binding Residues Provide Specificity for CpG DNA Methylation [Research Watch]

DNMT3A-DNMT3L-DNA crystal structures provide a mechanism for DNMT3A methyltransferase activity.

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Natural Killer Cells Recruit Dendritic Cells to Promote Antitumor Immunity [Research Watch]

Natural killer (NK) cells recruit conventional type 1 dendritic cells (cDC1) to the tumor microenvironment.

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Arvinas, Pfizer Team Up on PROTACs [News in Brief]

Proteolysis-targeting chimeras combat cancer by degrading disease-causing proteins.

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Editorial Board

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1





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Les big data, généralités et intégration en radiothérapie

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): C. Le Fèvre, L. Poty, G. Noël




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Bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for lung cancer: A case report

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): G. Fanetti, F. Bazzani, A. Ferrari, D. Alterio, S.M. Donghi, F.A. Pounou Kamga, R. Orecchia, B.A. Jereczek-Fossa
Bronchiolitis obliterans organizing pneumonia is an interstitial lung disease rarely occurring after radiotherapy probably due to an activation of autoimmune processes. Most cases have been described after postoperative radiotherapy for breast cancer. Corticosteroids represent the main treatment, prognosis is generally favorable. We described a case of bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for a recurrent lung cancer. Antibiotics and steroids were administered to solve the clinical picture. After three years, a new lesion at the right lung was found and treated with stereotactic ablative radiation therapy and concomitant long course of steroids with no recurrence of bronchiolitis obliterans organizing pneumonia. Bronchiolitis obliterans organizing pneumonia is a rare event after radiotherapy with undefined risk factors. In our case, steroids played an important role in management and, maybe, in preventing bronchiolitis obliterans organizing pneumonia recurrence after second course of stereotactic ablative radiation therapy.



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Issue Contents

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1





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Total body irradiation using Helical Tomotherapy®: Treatment technique, dosimetric results and initial clinical experience

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): V. Sarradin, L. Simon, A. Huynh, J. Gilhodes, T. Filleron, F. Izar
PurposeHelical TomoTherapy^® allows precise and homogeneous tumour coverage and excellent sparing of organs at risk. We present here our treatment technique, dosimetric results, and our first clinical data for patients receiving total body irradiation as part of the conditioning regimen before hematopoietic stem cell transplantation.Patients and methodsThe cohort consisted of 11 patients who were treated in our institution between August 2014 and January 2016. The total dose was 12Gy in six fractions in three days. We collected the dose distribution information in the treatment volumes, organs at risk and area of junction. We report retrospectively the clinical events during the first 6 months after the procedure.ResultsMedian age was 31 years (range, 18–57 years). Median D98% was 11.5Gy (range: 6.6–11.9Gy). The median of the mean doses to the lungs was 8.7Gy (range: 8.5–9.3Gy). The mean dose for the junction area was 12Gy (range: 11.9–12.1Gy). All patients had the total procedure, and all underwent successful engraftment. During the first six months, nine patients had at least one grade 3 or 4 toxicity that was due essentially to graft versus host disease. No patient had radiation pneumonitis. The toxicities were both more frequent and of higher grade during the first three months.ConclusionTotal body irradiation using helical TomoTherapy^® is feasible. It allows a very good homogeneity of dose and conformity with an acceptable tolerance. It could deliver higher doses to sites at high risk of recurrence (bone marrow, sanctuary sites), while sparing major normal organs like lungs, liver, and kidneys. This reduction of dose could lead to reduced severity and frequency of late complications.



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Adjuvant radiotherapy for positive lymph nodes of oesophageal squamous cell carcinoma: Can it earn promising benefits at long-term follow-up?

Publication date: Available online 14 February 2018
Source:Cancer/Radiothérapie
Author(s): Y. Ren, J. Ye, W. Xiong, J. Zuo, Y. He, M. Tan, Y. Yuan
PurposeThe value of adjuvant radiotherapy for patients with positive lymph nodes after curative resection of oesophageal squamous cell carcinoma is controversial. This study aims to investigate its long-term benefits in a specific cohort.Patients and MethodsThe charts between 1990 and 2003 from patients with positive lymph nodes were retrospectively reviewed. Those subjects were divided into adjuvant radiotherapy and surgery alone groups, with two subgroups defined by radiation dose (cutoff value: 50Gy). Overall survival, disease-free survival and locoregional recurrence-free survival were compared between two groups, with predictive factors of overall survival analysed meanwhile.ResultsIn sum, 175 matched patients with 1:2 ratios for group balance were enrolled for final analysis. During the follow-up (median: 37.0 months), 143 (81.7%) deaths were recorded, with 70.6% of deaths from cancer progression. The median overall survival time (19.5, 4 to 172 months) was not significantly different between the two groups (18.9 vs. 20.0 months, P=0.179). However, the disease-free survival time was significantly shorter in the adjuvant radiotherapy group than that in the control group (median, 11.5 vs. 14.9 months; P=0.001), with the locoregional recurrence-free survival time impressively prolonged (median: 18.3 vs. 16.5 months; P=0.022). Age (P=0.030), number (P=0.005) and ratio (P=0.002) of positive lymph nodes were associated with overall survival, but radiation dose was not (P=0.204).ConclusionAdjuvant radiotherapy with low- or high-dose did not improve survival compared with surgery alone. However, radiotherapy was effective to control locoregional recurrence, and could be applied as salvage therapy when recurrence event occurred.



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Investigation of electron boost radiotherapy in patients with breast cancer: Is a direct electron field optimal?

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): M. Aghili, M. Barzegartahamtan, A. Alikhassi, R. Mohammadpour
PurposeHistorically, electron boost dose mainly was delivered by a direct field in adjuvant radiotherapy of breast cancer. In this prospective study, we investigated direct electron field, in terms of optimal coverage of tumour bed volume following localization using ultrasound and surgical clips.Material and methodsFirst, for all 24 patients, a breast sonographer drew perimeter of tumour bed on the breast skin. Then an electron boost field was outlined on the demarcated territory, and a lead wire marker compatible with CT scan was placed on the field borders by a 2cm margin. After CT scan simulation, all patients underwent adjuvant whole breast irradiation with 3D-conformal radiotherapy to 50Gy in 25 fractions. Then for boost radiotherapy, lead wire in CT images was countoured as electron boost field. Also, the tumour bed was contoured based on surgical clips (true clinical target volume and true planning target volume). Electron treatment planning was done for electron boost field. Finally isodose coverages for true planning target volume investigated.ResultsOn average, 16.68% of clips planning target volume (true planning target volume; range: 0.00 to 95%) received 90% oor more of the prescribed dose when the electron treatment plan was made. Isodose curves does not provide adequate coverage on the tumour bed (clips planning target volume) when electron boost treatment planning was generated for electron boost field (en face electron field). In fact, a part of target (planning target volume-c) is missed and more doses is absorbed in normal tissue.ConclusionsElectron boost treatment planning (an en face electron field) following tumour bed localization using ultrasonography does not provide an optimized coverage of tumour bed volume.



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Editorial Board

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1





http://ift.tt/2Gl1Q87

Les big data, généralités et intégration en radiothérapie

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): C. Le Fèvre, L. Poty, G. Noël




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Issue Contents

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1





http://ift.tt/2FapgOl

Total body irradiation using Helical Tomotherapy®: Treatment technique, dosimetric results and initial clinical experience

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): V. Sarradin, L. Simon, A. Huynh, J. Gilhodes, T. Filleron, F. Izar
PurposeHelical TomoTherapy^® allows precise and homogeneous tumour coverage and excellent sparing of organs at risk. We present here our treatment technique, dosimetric results, and our first clinical data for patients receiving total body irradiation as part of the conditioning regimen before hematopoietic stem cell transplantation.Patients and methodsThe cohort consisted of 11 patients who were treated in our institution between August 2014 and January 2016. The total dose was 12Gy in six fractions in three days. We collected the dose distribution information in the treatment volumes, organs at risk and area of junction. We report retrospectively the clinical events during the first 6 months after the procedure.ResultsMedian age was 31 years (range, 18–57 years). Median D98% was 11.5Gy (range: 6.6–11.9Gy). The median of the mean doses to the lungs was 8.7Gy (range: 8.5–9.3Gy). The mean dose for the junction area was 12Gy (range: 11.9–12.1Gy). All patients had the total procedure, and all underwent successful engraftment. During the first six months, nine patients had at least one grade 3 or 4 toxicity that was due essentially to graft versus host disease. No patient had radiation pneumonitis. The toxicities were both more frequent and of higher grade during the first three months.ConclusionTotal body irradiation using helical TomoTherapy^® is feasible. It allows a very good homogeneity of dose and conformity with an acceptable tolerance. It could deliver higher doses to sites at high risk of recurrence (bone marrow, sanctuary sites), while sparing major normal organs like lungs, liver, and kidneys. This reduction of dose could lead to reduced severity and frequency of late complications.



http://ift.tt/2GmgqMQ

Adjuvant radiotherapy for positive lymph nodes of oesophageal squamous cell carcinoma: Can it earn promising benefits at long-term follow-up?

Publication date: Available online 14 February 2018
Source:Cancer/Radiothérapie
Author(s): Y. Ren, J. Ye, W. Xiong, J. Zuo, Y. He, M. Tan, Y. Yuan
PurposeThe value of adjuvant radiotherapy for patients with positive lymph nodes after curative resection of oesophageal squamous cell carcinoma is controversial. This study aims to investigate its long-term benefits in a specific cohort.Patients and MethodsThe charts between 1990 and 2003 from patients with positive lymph nodes were retrospectively reviewed. Those subjects were divided into adjuvant radiotherapy and surgery alone groups, with two subgroups defined by radiation dose (cutoff value: 50Gy). Overall survival, disease-free survival and locoregional recurrence-free survival were compared between two groups, with predictive factors of overall survival analysed meanwhile.ResultsIn sum, 175 matched patients with 1:2 ratios for group balance were enrolled for final analysis. During the follow-up (median: 37.0 months), 143 (81.7%) deaths were recorded, with 70.6% of deaths from cancer progression. The median overall survival time (19.5, 4 to 172 months) was not significantly different between the two groups (18.9 vs. 20.0 months, P=0.179). However, the disease-free survival time was significantly shorter in the adjuvant radiotherapy group than that in the control group (median, 11.5 vs. 14.9 months; P=0.001), with the locoregional recurrence-free survival time impressively prolonged (median: 18.3 vs. 16.5 months; P=0.022). Age (P=0.030), number (P=0.005) and ratio (P=0.002) of positive lymph nodes were associated with overall survival, but radiation dose was not (P=0.204).ConclusionAdjuvant radiotherapy with low- or high-dose did not improve survival compared with surgery alone. However, radiotherapy was effective to control locoregional recurrence, and could be applied as salvage therapy when recurrence event occurred.



http://ift.tt/2F97OK7

Investigation of electron boost radiotherapy in patients with breast cancer: Is a direct electron field optimal?

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): M. Aghili, M. Barzegartahamtan, A. Alikhassi, R. Mohammadpour
PurposeHistorically, electron boost dose mainly was delivered by a direct field in adjuvant radiotherapy of breast cancer. In this prospective study, we investigated direct electron field, in terms of optimal coverage of tumour bed volume following localization using ultrasound and surgical clips.Material and methodsFirst, for all 24 patients, a breast sonographer drew perimeter of tumour bed on the breast skin. Then an electron boost field was outlined on the demarcated territory, and a lead wire marker compatible with CT scan was placed on the field borders by a 2cm margin. After CT scan simulation, all patients underwent adjuvant whole breast irradiation with 3D-conformal radiotherapy to 50Gy in 25 fractions. Then for boost radiotherapy, lead wire in CT images was countoured as electron boost field. Also, the tumour bed was contoured based on surgical clips (true clinical target volume and true planning target volume). Electron treatment planning was done for electron boost field. Finally isodose coverages for true planning target volume investigated.ResultsOn average, 16.68% of clips planning target volume (true planning target volume; range: 0.00 to 95%) received 90% oor more of the prescribed dose when the electron treatment plan was made. Isodose curves does not provide adequate coverage on the tumour bed (clips planning target volume) when electron boost treatment planning was generated for electron boost field (en face electron field). In fact, a part of target (planning target volume-c) is missed and more doses is absorbed in normal tissue.ConclusionsElectron boost treatment planning (an en face electron field) following tumour bed localization using ultrasonography does not provide an optimized coverage of tumour bed volume.



http://ift.tt/2GlCUxz

Bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for lung cancer: A case report

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): G. Fanetti, F. Bazzani, A. Ferrari, D. Alterio, S.M. Donghi, F.A. Pounou Kamga, R. Orecchia, B.A. Jereczek-Fossa
Bronchiolitis obliterans organizing pneumonia is an interstitial lung disease rarely occurring after radiotherapy probably due to an activation of autoimmune processes. Most cases have been described after postoperative radiotherapy for breast cancer. Corticosteroids represent the main treatment, prognosis is generally favorable. We described a case of bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for a recurrent lung cancer. Antibiotics and steroids were administered to solve the clinical picture. After three years, a new lesion at the right lung was found and treated with stereotactic ablative radiation therapy and concomitant long course of steroids with no recurrence of bronchiolitis obliterans organizing pneumonia. Bronchiolitis obliterans organizing pneumonia is a rare event after radiotherapy with undefined risk factors. In our case, steroids played an important role in management and, maybe, in preventing bronchiolitis obliterans organizing pneumonia recurrence after second course of stereotactic ablative radiation therapy.



http://ift.tt/2FaPYX4

Les big data, généralités et intégration en radiothérapie

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): C. Le Fèvre, L. Poty, G. Noël




http://ift.tt/2GkLIDG

Les big data, généralités et intégration en radiothérapie

Publication date: February 2018
Source:Cancer/Radiothérapie, Volume 22, Issue 1
Author(s): C. Le Fèvre, L. Poty, G. Noël




http://ift.tt/2HqbkR6

Dose–response curves for MRI-detected radiation-induced temporal lobe reactions in patients after proton and carbon ion therapy: Does the same RBE-weighted dose lead to the same biological effect?

To derive the dose–response curve for temporal lobe reactions (TLRs) after proton therapy and to compare the resulting relative biological effectiveness (RBE)-weighted tolerance doses based on an RBE of 1.1 with published values for carbon ions, which were calculated by the two versions of the local effect model (LEM I or IV).

http://ift.tt/2BwXZ90

A statistical comparison of motion mitigation performances and robustness of various pencil beam scanned proton systems for liver tumour treatments

Different scanned proton therapy systems provide different scanning scenarios, directly changing the temporal interference between sequential beam delivery and tumour motion. We aim here to quantify the interplay effects and compare motion mitigation performance among different PBS scanning systems.

http://ift.tt/2C3ex9A

In Response

No abstract available

http://ift.tt/2BvxYqF

In Response

No abstract available

http://ift.tt/2ExMdhh

Perioperative Inflammation and Its Modulation by Anesthetics

Surgery and other invasive procedures, which are routinely performed during general anesthesia, may induce an inflammatory response in the patient. This inflammatory response is an inherent answer of the body to the intervention and can be both beneficial and potentially harmful. The immune system represents a unique evolutionary achievement equipping higher organisms with an effective defense mechanism against exogenous pathogens. However, not only bacteria might evoke an immune response but also other noninfectious stimuli like the surgical trauma or mechanical ventilation may induce an inflammatory response of varying degree. In these cases, the immune system activation is not always beneficial for the patients and might carry the risk of concomitant, harmful effects on host cells, tissues, or even whole organ systems. Research over the past decades has contributed substantial information in which ways surgical patients may be affected by inflammatory reactions. Modulations of the patient's immune system may be evoked by the use of anesthetic agents, the nature of surgical trauma and the use of any supportive therapy during the perioperative period. The effects on the patient may be manifold, including various proinflammatory effects. This review focuses on the causes and effects of inflammation in the perioperative period. In addition, we also highlight possible approaches by which inflammation in the perioperative may be modulated in the future.

http://ift.tt/2BAaVep

Perioperative Cardiac Arrest: Focus on Local Anesthetic Systemic Toxicity (LAST)

No abstract available

http://ift.tt/2o5nN4D

Macintosh Blade Videolaryngoscopy Combined With Rigid Bonfils Intubation Endoscope Offers a Suitable Alternative for Patients With Difficult Airways

BACKGROUND: In the armamentarium of an anesthesiologist, videolaryngoscopy is a valuable addition to secure the airway. However, when the videolaryngoscope (VLS) offers no solution, few options remain. Earlier, we presented an intubation technique combining Macintosh blade VLS and Bonfils intubation endoscope (BIE) for a patient with a history of very difficult intubation. In the present study, we evaluated this technique to establish whether it is a valuable alternative. METHODS: In this single-blinded nonrandomized study, 38 patients with a history of difficult intubation or 1 or more predictors of difficult intubation, scoring a Cormack & Lehane (C&L) grade III or IV using Macintosh blade VLS, were included. Patients were intubated combining the VLS with the BIE. The C&L grade was scored 3 times during (1) direct laryngoscopy; (2) indirect videolaryngoscopy; and (3) using the combined technique (VLS + BIE). Afterward, 2 blinded anesthesiologists assessed the C&L grade using the pictures taken during the procedure. RESULTS: Data of 38 patients were analyzed. An improvement of the C&L grade with the combined technique occurred in 33 of 38 patients (86.8%; 95% confidence interval, 71.9%–95.6%). Reviewer 1 reported an improvement of the C&L grade with the combined technique in 37 of 38 patients. Reviewer 2 reported improvement in 33 and deterioration in 2 of the patients. No complications occurred. CONCLUSIONS: The combined use of a VLS with Macintosh blade and BIE gives the anesthesiologist a valuable alternative intubation option in patients with extremely difficult airways.

http://ift.tt/2C2xFEM

Perioperative Cardiac Arrest: Focus on Malignant Hyperthermia (MH)

No abstract available

http://ift.tt/2odiwXN

In Response

No abstract available

http://ift.tt/2Bvya9n

Post-Cardiac Arrest Management: Time to Cool It on Cooling?

No abstract available

http://ift.tt/2o4NMsD

Efficacy Outcome Measures for Pediatric Procedural Sedation Clinical Trials: An ACTTION Systematic Review

Objective evaluations comparing different techniques and approaches to pediatric procedural sedation studies have been limited by a lack of consistency among the outcome measures used in assessment. This study reviewed those existing measures, which have undergone psychometric analysis in a pediatric procedural sedation setting, to determine to what extent and in what circumstances their use is justified across the spectrum of procedures, age groups, and techniques. The results of our study suggest that a wide range of measures has been used to assess the efficacy and effectiveness of pediatric procedural sedation. Most lack the evidence of validity and reliability that is necessary to facilitate rigorous clinical trial design, as well as the evaluation of new drugs and devices. A set of core pediatric sedation outcome domains and outcome measures can be developed on the basis of our findings. We believe that consensus among all stakeholders regarding appropriate domains and measures to evaluate pediatric procedural sedation is possible and that widespread implementation of such recommendations should be pursued.

http://ift.tt/2ExLXPl

Meta-analysis, Medical Reversal, and Settled Science

No abstract available

http://ift.tt/2ocV1hI

The Effect of Adductor Canal Block on Knee Extensor Muscle Strength 6 Weeks After Total Knee Arthroplasty: A Randomized, Controlled Trial

BACKGROUND: Total knee arthroplasty (TKA) reduces knee extensor muscle strength (KES) in the operated limb for several months after the surgery. Immediately after TKA, compared to either inguinal femoral nerve block or placebo, adductor canal block (ACB) better preserves KES. Whether this short-term increase in KES is maintained several weeks after surgery remains unknown. We hypothesized that 48 hours of continuous ACB immediately after TKA would improve KES 6 weeks after TKA, compared to placebo. METHODS: Patients scheduled for primary unilateral TKA were randomized to receive either a continuous ACB (group ACB) or a sham block (group SHAM) for 48 hours after surgery. Primary outcome was the difference in maximal KES 6 weeks postoperatively, measured with a dynamometer during maximum voluntary isometric contraction. Secondary outcomes included postoperative day 1 (POD1) and day 2 (POD2) KES, pain scores at rest and peak effort, and opioid consumption; variation at 6 weeks of Knee Osteoarthritis Outcome Score, patient satisfaction, and length of hospital stay. RESULTS: Sixty-three subjects were randomized and 58 completed the study. Patients in group ACB had less pain at rest during POD1 and during peak effort on POD1 and POD2, consumed less opioids on POD1 and POD2, and had higher median KES on POD1. There was no significant difference between groups for median KES on POD2, variation of Knee Osteoarthritis Outcome Score, patient satisfaction, and length of stay. There was no difference between groups in median KES 6 weeks after surgery (52 Nm [31–89 Nm] for group ACB vs 47 Nm [30–78 Nm] for group SHAM, P= .147). CONCLUSIONS: Continuous ACB provides better analgesia and KES for 24–48 hours after surgery, but does not affect KES 6 weeks after TKA. Further research could evaluate whether standardized and optimized rehabilitation over the long term would allow early KES improvements with ACB to be maintained over a period of weeks or months.

http://ift.tt/2ByHqJD

Motor Evoked Potential Monitoring During Thoracoabdominal Aortic Surgery: Useful or Not?

No abstract available

http://ift.tt/2o5iEcF

You’re Wrong, I’m Right: Dueling Authors Reexamine Classic Teachings in Anesthesia

No abstract available

http://ift.tt/2C3hyGZ

The Night Shift Nightmare

No abstract available

http://ift.tt/2ocuKzS

Anesthesia Advanced Cardiac Life Support: A Guideline Validated?

No abstract available

http://ift.tt/2o2ngAs

Perioperative Cardiac Arrest: Focus on Anaphylaxis

No abstract available

http://ift.tt/2obsSaP

Hyperglycemia and Elevated Lactate in Trauma: Where Do We Go From Here?

No abstract available

http://ift.tt/2ocsY1E

A Retrospective Analysis of Clinical Research Misconduct Using FDA-Issued Warning Letters and Clinical Investigator Inspection List From 2010 to 2014

BACKGROUND: The US Food and Drug Administration (FDA) conducts inspections of clinical investigation sites as a component of clinical trial regulation. The FDA describes the results of these inspections in the Clinical Investigator Inspection List (CLIIL). More serious violations are followed up in FDA warning letters issued to investigators. The primary objective of the current study is to qualitatively and quantitatively describe the CLIIL data and contents of FDA-issued warning letters from 2010 to 2014. METHODS: We retrospectively analyzed the CLIIL and FDA warning letters. For the CLIIL, we quantified the frequency of each violation among other data points. We compared recent data (2010–2014) to the previous 5 years (2005–2009). To analyze FDA warning letters, we developed a coding system to quantify the frequency of violations found. RESULTS: We analyzed 3637 inspections in the CLIIL database and 60 warning letters. Overall, there was a decrease or no change in all violations in the CLIIL database. The largest violation code reported was "failure to follow investigational plan" in both the 2005–2009 and 2010–2014 timeframes. Coding of FDA warning letters shows that the most common violations reported were failing to maintain accurate case histories (10.82%), enrolling ineligible subjects (8.85%), and failing to perform required tests (8.52%). CONCLUSIONS: The overall decrease in violations is encouraging. But, the high proportion of violations related to failure to follow the investigational plan is concerning as the complexity of trials increases. We conclude that more detailed information is necessary to accurately evaluate these violations. The current study provides a model for creating more granular data of violations to better inform clinical investigators and improve clinical trials.

http://ift.tt/2C2Vw7s

Between a ROCK and an IR Place

No abstract available

http://ift.tt/2o2neZm

Chinese Anesthesiologists Have High Burnout and Low Job Satisfaction: A Cross-Sectional Survey

BACKGROUND: The Chinese health care system must meet the needs of 19% of the world's population. Despite recent economic growth, health care resources are unevenly distributed. This creates the potential for job stress and burnout. We therefore conducted a survey among anesthesiologists in the Beijing–Tianjin–Hebei region focusing on job satisfaction and burnout to determine the incidence and associated factors. METHODS: A large cross-sectional study was performed in the Beijing–Tianjin–Hebei region of China. The anonymous questionnaire was designed to collect and analyze the following information: (1) demographic characteristics and employer information; (2) job satisfaction assessed by Minnesota Satisfaction Questionnaire; (3) burnout assessed by Maslach Burnout Inventory-Human Service Survey; and (4) sleep pattern and physician–patient communication. RESULTS: Surveys were completed and returned from 211 hospitals (response rate 74%) and 2873 anesthesiologists (response rate 70%) during the period of June to August 2015. The overall job satisfaction score of Minnesota Satisfaction Questionnaire was 65.3 ± 11.5. Among the participants, 69% (95% confidence interval [CI], 67%–71%) met the criteria for burnout. The prevalence of high emotional exhaustion, high depersonalization, and low personal accomplishment was 57% (95% CI, 55%–59%), 49% (95% CI, 47%–51%), and 57% (95% CI, 55%–58%), respectively. Using multivariable logistic regression analysis, we found that age, hospital category, working hours per week, caseload per day, frequency of perceived challenging cases, income, and sleep quality were independent variables associated with burnout. Anesthesiologists with a high level of depersonalization tended to engage in shorter preoperative conversations with patients, provide less information about pain or the procedure, and to have less empathy with them. CONCLUSIONS: The anesthesiologists in the Beijing–Tianjin–Hebei region of China expressed a below-average level of job satisfaction, and suffered a significant degree of burnout. Improvement in job satisfaction and burnout might create a positive work climate that could benefit both the quality of patient care and the profession of anesthesiology in China.

http://ift.tt/2BAaLUl

Provider Variability in Intensity Modulated Radiation Therapy Utilization among Medicare Beneficiaries in the United States

Publication date: Available online 16 February 2018
Source:Practical Radiation Oncology
Author(s): Stephen R. Grant, Benjamin D. Smith, Anna O. Likhacheva, Shervin M. Shirvani, David B. Rosen, B. Ashleigh Guadagnolo, Dean A. Shumway, Emma B. Holliday, Daniel Chamberlain, Gary V. Walker
BackgroundIn this study, we sought to examine the variation in intensity modulated radiation therapy (IMRT) use among radiation oncology providersMethodsThe Medicare Physician and Other Supplier Public Use File was queried for radiation oncologists practicing during 2014. Healthcare Common Procedural Coding System code 77301 was designated as IMRT planning with metrics including number of total IMRT plans, rate of IMRT utilization, and number of IMRT plans per distinct beneficiary.ResultsOf 2,759 radiation oncologists, the median number of total IMRT plans was 26 (mean 33.4, SD 26.2, range 11 to 321) with a median IMRT utilization rate of 36% (mean 43%, SD 25%, range 4% to 100%) and a median number of IMRT plans per beneficiary of 1.02 (mean 1.07, range 1.00 to 3.73). On multivariable analysis, increased IMRT utilization was associated with male gender, academic practice, technical fee billing, freestanding practice, practice in a county with 21 or more radiation oncologists, and practice in the South.(p<0.05). The top one percent of utilizers (28 providers) billed a mean 181 IMRT plans with an IMRT utilization rate of 66% and 1.52 IMRT plans per beneficiary. Of these 28 providers, 24 had billed technical fees, 25 practiced in freestanding clinics, and 20 practiced in the South.ConclusionsTechnical fee billing, freestanding practice, male gender, and location in the South were associated with one or more metrics of increased IMRT use. A small group of outliers shared several common demographic and practice-based characteristics.



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Stereotactic radiosurgery for benign brain tumours: Results of multi-centre benchmark planning studies

Publication date: Available online 16 February 2018
Source:Practical Radiation Oncology
Author(s): David J. Eaton, Jonathan Lee, Rushil Patel, Antony E. Millin, Ian Paddick, Christopher Walker
PurposeStereotactic radiosurgery (SRS) is strongly indicated for treatment of surgically inaccessible benign brain tumours. Various treatment platforms are available, but few comparisons have included multiple centres. As part of a national commissioning programme, benchmark planning cases were completed by all clinical centres in the region.Methods and MaterialsFour benign cases were provided, with images and structures pre-delineated: intracanalicular vestibular schwannoma (VS), larger VS, skull base meningioma and secreting pituitary adenoma. Centres were asked to follow their local practice, and plans were reviewed centrally using metrics for target coverage, selectivity, gradient fall-off and normal tissue sparing.Results68 plans were submitted, using 18 different treatment platforms. 14 plans were subsequently revised following feedback, and review of 5 plans led to a restriction of service on 2 platforms (2 centres).Prescription doses were consistent for VS and meningioma submissions, but a wide range of doses were used for the pituitary case. All centres prioritised coverage, with the prescription isodose covering ≥95% of 78/82 target volumes. Lower values may be expected next to air cavities when using advanced algorithms, and in general may be acceptable for some benign lesions. Selectivity was much more variable, and in some cases this was combined with high gradient index and/or >1mm margin, resulting in large volumes of normal tissue being irradiated. Normal tissue doses were more variable across linac-based plans than Gamma Knife or Cyberknife, and dose spillage seemed independent of prescription isodose (inhomogeneity). This may reflect the variety of linac-based approaches represented, or the necessary trade-off between different objectives.ConclusionsThese benchmarking exercises have highlighted areas of different clinical practice and priorities, and potential for improvement. The subsequent sharing of plan data and margin philosophies between the neurosurgery and oncology communities allowed for meaningful comparison between centres and their peers.



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The role of proton beam therapy in central neurocytoma: a single-institution experience

Publication date: Available online 16 February 2018
Source:Practical Radiation Oncology
Author(s): Kylie H. Kang, Emily Schapira, Andrzej Niemierko, Maria Martinez-Lage, Marc R. Bussière, Torunn I. Yock, Jay S. Loeffler, William E. Butler, Bob S. Carter, Helen A. Shih
PurposeCentral neurocytomas (CN) are rare WHO grade II tumors managed with surgery and radiation therapy. We report our experience in managing CN with proton beam therapy (PBT) when radiation therapy was employed.Methods and MaterialsWe identified 61 patients with pathologically-diagnosed CN treated at our institution between 1996-2016, of which 24 met inclusion criteria. Patient, tumor, and treatment characteristics are reported in context of progression-free survival and treatment-related adverse effects.ResultsOf 24 patients identified, median age at diagnosis was 21 years (range: 14 - 60). Median maximal tumor diameter was 4.5 cm (range: 1.4 - 6.8). Eighteen (75%) patients underwent upfront surgery alone. Sixteen (67%) patients received adjuvant or salvage PBT at a median dose of 54 Gy(RBE). Median follow-up was 56 months. Median progression-free survival (PFS) was 61 months. Eleven patients had disease progression with median time to progression of 22 months. Of the five patients with gross total resection, four experienced local recurrence and had MIB-1>4% (range: 4.5 - 30). There was improved PFS with addition of PBT to definitive surgery (log-rank, p=.06); there was no disease progression to date. In patients who experienced disease recurrence/progression, MIB-1<4% was associated with improved PFS (log-rank, p=.007). All patients tolerated PBT well with toxicities typical for cranial irradiation and with no grade ≥3 toxicities.ConclusionIn our cohort, CN with elevated MIB-1 index were at increased risk for disease progression. However, adjuvant radiotherapy appears to effectively prevent failure. PBT toxicities appear to be comparable if not less than published photon experiences.



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Provider Variability in Intensity Modulated Radiation Therapy Utilization among Medicare Beneficiaries in the United States

Publication date: Available online 16 February 2018
Source:Practical Radiation Oncology
Author(s): Stephen R. Grant, Benjamin D. Smith, Anna O. Likhacheva, Shervin M. Shirvani, David B. Rosen, B. Ashleigh Guadagnolo, Dean A. Shumway, Emma B. Holliday, Daniel Chamberlain, Gary V. Walker
BackgroundIn this study, we sought to examine the variation in intensity modulated radiation therapy (IMRT) use among radiation oncology providersMethodsThe Medicare Physician and Other Supplier Public Use File was queried for radiation oncologists practicing during 2014. Healthcare Common Procedural Coding System code 77301 was designated as IMRT planning with metrics including number of total IMRT plans, rate of IMRT utilization, and number of IMRT plans per distinct beneficiary.ResultsOf 2,759 radiation oncologists, the median number of total IMRT plans was 26 (mean 33.4, SD 26.2, range 11 to 321) with a median IMRT utilization rate of 36% (mean 43%, SD 25%, range 4% to 100%) and a median number of IMRT plans per beneficiary of 1.02 (mean 1.07, range 1.00 to 3.73). On multivariable analysis, increased IMRT utilization was associated with male gender, academic practice, technical fee billing, freestanding practice, practice in a county with 21 or more radiation oncologists, and practice in the South.(p<0.05). The top one percent of utilizers (28 providers) billed a mean 181 IMRT plans with an IMRT utilization rate of 66% and 1.52 IMRT plans per beneficiary. Of these 28 providers, 24 had billed technical fees, 25 practiced in freestanding clinics, and 20 practiced in the South.ConclusionsTechnical fee billing, freestanding practice, male gender, and location in the South were associated with one or more metrics of increased IMRT use. A small group of outliers shared several common demographic and practice-based characteristics.



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Stereotactic radiosurgery for benign brain tumours: Results of multi-centre benchmark planning studies

Publication date: Available online 16 February 2018
Source:Practical Radiation Oncology
Author(s): David J. Eaton, Jonathan Lee, Rushil Patel, Antony E. Millin, Ian Paddick, Christopher Walker
PurposeStereotactic radiosurgery (SRS) is strongly indicated for treatment of surgically inaccessible benign brain tumours. Various treatment platforms are available, but few comparisons have included multiple centres. As part of a national commissioning programme, benchmark planning cases were completed by all clinical centres in the region.Methods and MaterialsFour benign cases were provided, with images and structures pre-delineated: intracanalicular vestibular schwannoma (VS), larger VS, skull base meningioma and secreting pituitary adenoma. Centres were asked to follow their local practice, and plans were reviewed centrally using metrics for target coverage, selectivity, gradient fall-off and normal tissue sparing.Results68 plans were submitted, using 18 different treatment platforms. 14 plans were subsequently revised following feedback, and review of 5 plans led to a restriction of service on 2 platforms (2 centres).Prescription doses were consistent for VS and meningioma submissions, but a wide range of doses were used for the pituitary case. All centres prioritised coverage, with the prescription isodose covering ≥95% of 78/82 target volumes. Lower values may be expected next to air cavities when using advanced algorithms, and in general may be acceptable for some benign lesions. Selectivity was much more variable, and in some cases this was combined with high gradient index and/or >1mm margin, resulting in large volumes of normal tissue being irradiated. Normal tissue doses were more variable across linac-based plans than Gamma Knife or Cyberknife, and dose spillage seemed independent of prescription isodose (inhomogeneity). This may reflect the variety of linac-based approaches represented, or the necessary trade-off between different objectives.ConclusionsThese benchmarking exercises have highlighted areas of different clinical practice and priorities, and potential for improvement. The subsequent sharing of plan data and margin philosophies between the neurosurgery and oncology communities allowed for meaningful comparison between centres and their peers.



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The role of proton beam therapy in central neurocytoma: a single-institution experience

Publication date: Available online 16 February 2018
Source:Practical Radiation Oncology
Author(s): Kylie H. Kang, Emily Schapira, Andrzej Niemierko, Maria Martinez-Lage, Marc R. Bussière, Torunn I. Yock, Jay S. Loeffler, William E. Butler, Bob S. Carter, Helen A. Shih
PurposeCentral neurocytomas (CN) are rare WHO grade II tumors managed with surgery and radiation therapy. We report our experience in managing CN with proton beam therapy (PBT) when radiation therapy was employed.Methods and MaterialsWe identified 61 patients with pathologically-diagnosed CN treated at our institution between 1996-2016, of which 24 met inclusion criteria. Patient, tumor, and treatment characteristics are reported in context of progression-free survival and treatment-related adverse effects.ResultsOf 24 patients identified, median age at diagnosis was 21 years (range: 14 - 60). Median maximal tumor diameter was 4.5 cm (range: 1.4 - 6.8). Eighteen (75%) patients underwent upfront surgery alone. Sixteen (67%) patients received adjuvant or salvage PBT at a median dose of 54 Gy(RBE). Median follow-up was 56 months. Median progression-free survival (PFS) was 61 months. Eleven patients had disease progression with median time to progression of 22 months. Of the five patients with gross total resection, four experienced local recurrence and had MIB-1>4% (range: 4.5 - 30). There was improved PFS with addition of PBT to definitive surgery (log-rank, p=.06); there was no disease progression to date. In patients who experienced disease recurrence/progression, MIB-1<4% was associated with improved PFS (log-rank, p=.007). All patients tolerated PBT well with toxicities typical for cranial irradiation and with no grade ≥3 toxicities.ConclusionIn our cohort, CN with elevated MIB-1 index were at increased risk for disease progression. However, adjuvant radiotherapy appears to effectively prevent failure. PBT toxicities appear to be comparable if not less than published photon experiences.



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Recurrent epistaxis leading to diagnosis of primary sinonasal melanoma

A 48-year-old man presented to urgent care with recurrent epistaxis over 6 months. Initially, nosebleeds were controlled with packing or cautery. Ultimately, he was referred to ear, nose and throat department and underwent nasal endoscopy which revealed polypoid tissue. A biopsy of the polyp showed non-specific inflammation with no evidence of malignancy. Follow-up maxillofacial CT revealed a large mass lesion in the right maxillary sinus, right nasal fossa, much of the ethmoids and right sphenoid, with destruction of adjacent bony structures. MRI revealed a mass in the right nasal cavity with extension into the ethmoid and anterior sphenoid sinus, anterior cranial fossa and medial orbits. Staging CT discovered metastatic disease in the adrenal glands and lymphadenopathy in the neck. The patient underwent endoscopic sinus surgery with debulking and tissue diagnosis of malignant melanoma. He completed radiation therapy to sinus and was subsequently enrolled in a clinical trial. Most recent imaging revealed complete metabolic response on positron emission tomography.

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Polymicrobial bacterial pericarditis and cardiac tamponade caused by pericardial penetration of an adjustable gastric band

We describe a case of polymicrobial bacterial pericarditis with Klebsiella pneumoniae and Proteus mirabilis, caused by pericardial penetration of the tip of the catheter of a laparoscopic adjustable gastric band (LAGB). The patient developed a cardiac tamponade, and subsequently emergency pericardiocentesis was performed. Analysis of earlier CT scans showed that the tip of the catheter had migrated through the liver and through the diaphragm into the pericardium, and was in contact with the myocardium. After stabilisation he was operated to remove the LAGB. In this case report, we describe the chain of events that led to the polymicrobial pericarditis—a complication of LAGB placement that to our knowledge has thus far never been reported. We furthermore present a detailed literature review of all published cases of polymicrobial pericarditis and its causes.

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Renal nutcracker syndrome in a young lady: unusual findings and endovascular management

Nutcracker syndrome (NCS) is caused by compression of left renal vein (LRV), usually between the aorta and the superior mesenteric artery (SMA). This can lead to obstruction of flow into the inferior vena cava and secondary left renal venous hypertension. Despite potential serious consequences, diagnosing NCS is often challenging, circuitous and commonly delayed. We report an extremely unique case of NCS. A 34-year-old woman presented with left flank pain and discomfort. On investigation, it was found that high pressure in the LRV, due to compression by the SMA, had led to a large venous aneurysm that had caused pelviureteric junction obstruction and hydronephrosis. Management was with stenting of the LRV and coil embolisation of the venous aneurysm with excellent clinical outcome.

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Fistulation between a colonic J-Pouch and the upper vagina in an irradiated pelvis: a rare complication following low anterior resection with colonic J-pouch anal anastomosis for rectal cancer

Formation of a colonic J-pouch with anastomosis to the rectal stump is an accepted form of reconstruction after low anterior resection (LAR) for rectal carcinoma. It is thought this can help prevent the onset of LAR syndrome as well as improve the quality of life in the first two years following surgery. Rectovaginal fistulation is a recognised complication of this form of surgery usually occurring because of technical failure leading to inclusion of the vaginal wall into the stapled anastomosis. We present an as of yet unreported case of fistulation between the upper horizontal staple line of a colonic J-pouch—the tip of the 'J'—which was formed extracorporeally with the posterior vaginal fornix. We postulate that pelvic irradiation was partly a causative factor alongside subsequent mechanical irritation. Ultimately, surgical intervention was required, following which the patient made a full recovery. Interposition of omentum may prevent this problem.

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The cat did it: erythema nodosum and additional atypical presentations of Bartonella henselae infection in immunocompetent hosts

A healthy patient presented with painful skin lesions on the anterior surface of her legs. Erythema nodosum was diagnosed but all the usual causes were ruled out. The finding of bilateral enlarged axillary lymph nodes with necrosis and granulomas led to the diagnosis of Bartonella infection, an unusual cause of erythema nodosum. Imaging also revealed splenomegaly and small para-aortic lymph nodes. Up to one quarter of the patients with cat-scratch disease present atypically, a considerably higher prevalence than previously reported. A comprehensive review of the literature (PubMed, since inception, all languages) revealed a remarkable array of unusual presentations which are summarised and briefly discussed.

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Implant of a left atrial appendage occluder device (Watchman) and leadless pacing system (Micra) through the same venous access in a single sitting

A left atrial appendage occluder device (Watchman) and leadless pacemaker (Micra) was implanted from a single right femoral vein access in a 73-year-old female patient with persistent atrial fibrillation and symptomatic tachy-brady syndrome and unable to take oral anticoagulants. Standard methods of implantation were followed for both procedures. The Watchman device was implanted first followed by dilatation of the same venous access site in order to implant Micra transcatheter pacing system. The patient tolerated the procedures well and there were no complications. At the end of 1 month, both the devices were found to be working well.

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Syncope and cardiogenic shock in an 80-year-old woman

Description

An 80-year-old woman presented with a 2-day history of breathlessness and syncope. Her medical history included Parkinson's disease and a recent diagnosis of myelodysplasia for which she had undergone a (painful) bone marrow aspiration 2 days earlier.

Presentation blood pressure (BP) was 69/38 mm Hg (and fell further to 59/40 mm Hg with impaired conscious level), heart rate 78, respiratory rate 17 and oxygen saturation 100% on air. Her presentation of ECG revealed anteroseptal Q waves with 1 mm ST segment elevation (figure 1).

Figure 1

A 12-lead ECG at presentation.

Emergency primary percutaneous coronary intervention was declined due to the probability of established myocardial infarction with consequent cardiogenic shock. Medical treatment and inotropic therapy with intra-aortic balloon pump (IABP) were directed. She underwent emergency portable echocardiography to understand the aetiology for cardiogenic shock.

The panel of images (figure 2A–C)...

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Making a difference in the developing world

By Marcus Chong

In 2016, while conducting medical research in a rural village of Northern Samar, the Philippines, Professor Allen Ross and his global health research team met a patient with severe electrical burns. He was a construction worker who had suffered an electrical burn at work from an overhanging high voltage electrical wire carrying 20,000 Volts. He had sustained burns to 25% of his body with significant scarring on the skin under the armpits and the amputation of all four limbs.

After the accident, he was transported to a local hospital by a family member; he remained there without medical treatment for eight hours. Public hospitals in Metro Manila are typically overwhelmed – with a lack of physicians available to treat emergency patients. Approximately eight hours later an ambulance was found to transport the patient to a local burns centre. By then his untreated injuries had resulted in thromboses requiring amputations of all four limbs. His relative in Manila sold their company truck in order to pay for his surgical procedures and hospital care. He remained in hospital for a few weeks after the operation. At this point his family had used up all their savings. He was discharged in a wheelchair as physiotherapy, prostheses and rehabilitation were prohibitively expensive. He returned to his home village in Simora Palapag, Northern Samar (Image, left).

The published BMJ case report that resulted can be found here.

In 2017, with the patient and family's consent, Thao Ross (Allen's wife) organised crowd funding on a Go-fund-me website. Funds came from people of all walks of life. It took several months to raise the required funds for four prosthetic limbs.

We were able to buy prostheses made of aluminium and coated with an alloy that made them durable and water-proof in Manila, from the prosthetic limb company Ottobock. There were also sufficient funds to provide the patient with rehabilitation and prosthetic fitting services. The prostheses provided by the company for the lower limbs can be seen in the above image (right) and the patient is currently (2018) having his upper limbs custom made and fitted. The patient was able to walk again after a few weeks of physiotherapy and rehabilitation. The patient waited almost seven years to walk again and we are very happy to have made this possible!

Competing Interests

None Declared

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Barriers to accessing palliative care for pediatric patients with cancer: A review of the literature

Although many of the 16,000 children in the United States diagnosed who are with cancer each year could benefit from pediatric palliative care, these services remain underused. Evidence regarding the barriers impeding access to comprehensive palliative care is dispersed in the literature, and evidence specific to pediatric oncology remains particularly sparse. The purpose of the current review was to synthesize the existing literature regarding these barriers and the strategies offered to address them. The authors completed a literature search using the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science databases. In total, 71 articles were reviewed. Barriers to accessing pediatric palliative care were categorized according to the 4 levels of a modified socioecological model (ie, barriers related to policy/payment, health systems, organizations, and individuals). Major themes identified at each level included: 1) the lack of consistent and adequate funding mechanisms at the policy/payment level, 2) the lack of pediatric palliative care programs and workforce at the health systems level, 3) difficulties integrating palliative care into existing pediatric oncology care models at the organizational level, and 4) the lack of knowledge about pediatric palliative care, discomfort with talking about death, and cultural differences between providers and patients and their families at the individual level. Recommendations to address each of the barriers identified in the literature are included. Cancer 2018. © 2018 American Cancer Society.

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Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California

BACKGROUND

To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML).

METHODS

Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis).

RESULTS

Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs.

CONCLUSIONS

The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018. © 2018 American Cancer Society.

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Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non–small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2

BACKGROUND

The best treatment for patients with advanced non–small cell lung cancer (NSCLC) and a poor performance status is not well defined. In this phase 2 trial, patients were randomized to receive treatment with either single-agent pemetrexed or 1 of 2 combination regimens.

METHODS

Patients with newly diagnosed, histologically confirmed nonsquamous NSCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 were stratified by age and serum albumin level and were randomized (1:1:1) to 1 of 3 regimens: pemetrexed (arm 1), pemetrexed and bevacizumab (arm 2), or pemetrexed, carboplatin, and bevacizumab (arm 3). The response to treatment was assessed every 2 cycles; responding and stable patients continued treatment until progression or unacceptable toxicity.

RESULTS

One hundred seventy-two patients were randomized, 162 patients began the study treatment, and 146 patients completed 2 cycles and were evaluated for their response. The median progression-free survival (PFS) was 2.8 months in arm 1, 4.0 months in arm 2, and 4.8 months in arm 3. The overall response rates were 15% in arm 1, 31% in arm 2, and 44% in arm 3. The overall survival was similar in the 3 treatment arms. All 3 regimens were relatively well tolerated. Patients receiving bevacizumab had an increased incidence of hypertension, proteinuria, and bleeding episodes, but most events were mild or moderate.

CONCLUSIONS

All 3 regimens were feasible for patients with advanced NSCLC and an ECOG performance status of 2. The addition of bevacizumab to pemetrexed increased the overall response rate. The efficacy of pemetrexed/carboplatin/bevacizumab (median PFS, 4.8 months) approached the prespecified study PFS goal of 5 months. Larger studies will be necessary to define the role of bevacizumab in addition to standard pemetrexed and carboplatin in this population. Cancer 2018. © 2018 American Cancer Society.

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Phase 1b study of pasireotide, everolimus, and selective internal radioembolization therapy for unresectable neuroendocrine tumors with hepatic metastases

BACKGROUND

Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT.

METHODS

This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2.5, 5, and 10 mg/day), pasireotide (600 μg twice daily), and SIRT (SIR-Spheres dose on days 9 and 37). Eligibility criteria included well or moderately differentiated NETs, bilobar liver metastases, and progression on long-acting octreotide. Toxicities and responses were evaluated with the Common Terminology Criteria for Adverse Events and the Response Evaluation Criteria in Solid Tumors (version 1.1). Dose-limiting toxicities (DLTs) were defined in the first 28 days. Correlative markers—angiopoietin 1, angiopoietin 2, basic fibroblast growth factor, collagen V, insulin-like growth factor binding protein 1, insulin-like growth factor binding protein 1, interleukin 8, M30, M65, placenta growth factor, and vascular endothelial growth factor receptor 2—were assessed. The Norfolk Quality of Life–Neuroendocrine Tumor Questionnaire was used to assess the quality of life (QOL).

RESULTS

Thirteen patients were enrolled; 1 was not evaluable for the primary endpoint. Eleven patients had well-differentiated tumors. The primary sites included small bowel (4), pancreas (3), lung (2), colon (1), gastric (1), and unknown primary (2) were unknown. Four had liver-only disease; 12 completed the planned treatment. No DLTs were observed. There was no treatment-related mortality. The most common toxicity was hyperglycemia. Clinically significant liver toxicity was not observed. One patient had liver progression. QOL improved on treatment. The median progression-free survival and overall survival were 18.6 and 46.3 months, respectively.

CONCLUSIONS

The recommended phase 2 dose of everolimus is 10 mg daily in combination with pasireotide and SIRT. The regimen is well tolerated. Preliminary activity appears promising. Cancer 2018. © 2018 American Cancer Society.

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