Needs for Professional Education to Optimize Cervical Cancer Screenings in Low-Income Countries: a Case Study from Tanzania

Abstract

Cervical cancer is a significant health problem in many developing countries. Due to limited treatment facilities for cancer in Tanzania, a screening referral program was developed between two urban clinics and Ocean Road Cancer Institute (ORCI), the only cancer treatment center in Tanzania. This study aimed to evaluate the effectiveness of the program and to identify opportunities for professional education. The study included 139 patients who were referred to ORCI from the screening clinics of Magomeni and Temeke between January 2015 and May 2016. Abstracted data from the medical records included patient age, screening results, and treatment. Eight nurses performing screening at the three locations were interviewed about their screening experience. Over half of the referrals (51.9%) were false positives. False positive diagnosis was more common among younger patients (35.68 ± 8.6 years) (p < 0.001) and those referred from Magomeni (59.8%) (p < 0.01) than referrals of older patients (42.46 ± 11.1 years) or those from Temeke (33.3%). Interviews of nurses showed differences among clinics, including resources, experience, and documentation of screening results. The high false positive rates and the variation of accuracy of screening between the two clinics showed a need for professional education of nurses and improvement in the health systems. Continuous education of nurses may increase the effectiveness of cervical screening. Health system enhancement of screening facilities such as provision of Lugol's iodine, more space for screening, and consistency and completion of screening records are needed to increase the accuracy of cervical screening and referrals in Tanzania and other similar low-income countries.

http://ift.tt/2vP80IL

Gemcitabine and docetaxel in a patient with primary ovarian leiomyosarcoma: a case report and review of literature

Abstract

Primary ovarian leiomyosarcoma (POLMS) is extremely rare, and optimal therapy for this disease is unknown. A 40-year-old woman presented at a local hospital with abdominal pain. Tumor resection of the left ovary was performed. The pathological diagnosis was leiomyoma of the left ovary. Nine months after surgery, she developed of severe back pain and a subcutaneous tumor on her left shoulder. Magnetic resonance imaging and computed tomography revealed left ovarian tumor recurrence, pelvic bone metastasis, and multiple liver masses. Biopsy of the subcutaneous tumor on her left shoulder demonstrated metastatic leiomyosarcoma. The previously resected left ovarian tumor was re-examined, and the tumor was found to be a leiomyosarcoma. The patient received gemcitabine 800 mg/m² and docetaxel 60 mg/m² (GD therapy), administered at 3-week intervals. After three cycles of GD therapy, the patient experienced dyspnea and was diagnosed with mild interstitial pneumonia. Oral corticosteroid therapy resulted in complete symptom improvement. Thereafter, the dosage of GD was decreased, and after 13 cycles of GD therapy, radiofrequency ablation was performed twice for liver metastases. The tumors have shrunk by 65.5% after 23 cycles of GD. She remains alive after undergoing 24 cycles of GD. GD therapy may be effective for POLMS.

http://ift.tt/2wUi8Tw

Needs for Professional Education to Optimize Cervical Cancer Screenings in Low-Income Countries: a Case Study from Tanzania

Abstract

Cervical cancer is a significant health problem in many developing countries. Due to limited treatment facilities for cancer in Tanzania, a screening referral program was developed between two urban clinics and Ocean Road Cancer Institute (ORCI), the only cancer treatment center in Tanzania. This study aimed to evaluate the effectiveness of the program and to identify opportunities for professional education. The study included 139 patients who were referred to ORCI from the screening clinics of Magomeni and Temeke between January 2015 and May 2016. Abstracted data from the medical records included patient age, screening results, and treatment. Eight nurses performing screening at the three locations were interviewed about their screening experience. Over half of the referrals (51.9%) were false positives. False positive diagnosis was more common among younger patients (35.68 ± 8.6 years) (p < 0.001) and those referred from Magomeni (59.8%) (p < 0.01) than referrals of older patients (42.46 ± 11.1 years) or those from Temeke (33.3%). Interviews of nurses showed differences among clinics, including resources, experience, and documentation of screening results. The high false positive rates and the variation of accuracy of screening between the two clinics showed a need for professional education of nurses and improvement in the health systems. Continuous education of nurses may increase the effectiveness of cervical screening. Health system enhancement of screening facilities such as provision of Lugol's iodine, more space for screening, and consistency and completion of screening records are needed to increase the accuracy of cervical screening and referrals in Tanzania and other similar low-income countries.

http://ift.tt/2vP80IL

Molecular insights into the transcriptional regulatory role of thyroid hormones in ovarian cancer

Abstract

The regulation of cancer-relevant genes by the thyroid hormones, 3, 5, 3'-Triiodo-L-thyronine (T3) and L-thyroxine (T4), was recently acknowledged. However, limited data exists on the hormonal effects on gene expression in ovarian cancer, a gynecological malignancy associated with a low cure rate. The expression of fifteen genes involved in DNA repair, cell cycle, apoptosis and tumor suppression was evaluated in OVCAR-3 and A2780 cell lines, using real-time PCR following short incubation with T3 (1nM) or T4 (100nM). The thyroid hormones downregulated the expression of the majority of genes examined. Support for the involvement of the MAPK and PI3K in thyroid hormone-mediated gene expression was shown for a set of genes. FAS expression was inhibited in A2780 cells, while an unexpected induction was demonstrated in OVCAR-3 cells. An analogous effect on the protein levels of FAS receptor and its soluble form was demonstrated by western blotting. We further established, using primer sets that discriminate between the different RNA isoforms, that the hormones increase the mRNA levels of both coding and non-coding FAS mRNAs. The prevalence of these isoforms, using The Cancer Genome Atlas (TCGA) analysis, was significantly more abundant in seventeen cancer types, including ovarian cancer, compared to normal tissues. Our results highlight the role of thyroid hormones in the expression of cancer-relevant-genes in ovarian cancer and provide an important insight into the pathways by which mitogenic and anti-apoptotic effects are exerted. This article is protected by copyright. All rights reserved

http://ift.tt/2vZvvmK

Durable complete response in HER2-positive breast cancer: a multicenter retrospective analysis

Abstract

Purpose

Though advanced and metastatic epidermal growth factor receptor 2 (HER2)-positive disease is not curable, a small proportion of patients with HER2-positive metastatic breast cancer remain in prolonged complete remission with anti-HER2 treatment. We hypothesized that some cases of HER2-positive metastatic breast cancer may be curable. In this large, multicenter retrospective study, we aimed to assess the long-term outcomes for patients with a durable response to trastuzumab.

Methods

We retrospectively evaluated the data of patients diagnosed with HER2-positive metastatic breast cancer who received trastuzumab for more than 2 years as the first-line treatment. Patients diagnosed between April 1, 2001 and December 31, 2014 at 19 institutions in Japan were included in the analysis. From 124 potential subjects, 16 were excluded and 108 were evaluated.

Results

The median follow-up length was 7.7 years. Disease progression occurred in 44/108 (40.7%) patients and 13/108 (12%) patients died. The median progression-free survival was 11.2 years, and as more than 80% of patients were alive 10 years after metastatic breast cancer diagnosis. Of the 108 patients, 57 achieved a clinical complete response. Trastuzumab therapy was interrupted for 27 (47.4%) of these patients (based on the doctor's recommendation for 19 patients, owing to adverse events for 4 patients, owing to unknown reasons for 3 patients, and at the request of 1 patient). Disease progression occurred in 4 of the 27 patients after the interruption of trastuzumab treatment. The median duration of trastuzumab therapy for all 27 patients was 5.1 years (0.9–9.3 years).

Conclusion

We found that some patients showed no evidence of disease after the interruption of trastuzumab therapy. Discontinuation of maintenance trastuzumab in this patient population after a limited time should be explored cautiously while awaiting a global collaborative effort for a randomized trial.

http://ift.tt/2xYQumQ

Analysis of outcomes achieved with squamous cell carcinomas of the anus in a single university hospital over the last two decades: Clinical response rate, relapse and survival of 190 patients

Background and Objectives

We reviewed our series of anal squamous cell carcinomas (ASCC) treated over the last two decades.

Methods

ASCC patients undergoing treatment at the Leicester Royal Infirmary between 1998 and 2016 were selected. Age, gender, pathological tumor characteristics, treatment adopted, the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) at 5-year follow-up were recorded and calculated.

Results

A total of 190 ASCC were reviewed, of these 64.2% (n = 122) received primary radical chemoradiotherapy. Complete response rate was 92.6% (n = 113) and four patients with residual disease underwent a salvage APER. Twenty-eight patients experienced recurrent disease (23.0%) either systemic (n = 8), local (n = 14), or both (n = 6); six had a salvage APER. Complete follow-up data are available for 63.1% patients (77/122). Overall, the locoregional failure rate of primary chemoradiotherapy (residual + recurrent disease) was present in 29 patients (29/122; 23.8%). OS was 41.6% CSS was 69.2% and DFS 60.0% at 5 years follow-up.

Conclusions

In our series of ASCC primary chemoradiotherapy had achieved significant initial complete response rates, however, long term-follow ups still present systemic and local recurrences. APR is able to treat 30% of the pelvic recurrences (6/20), the others are either associated with systemic disease or locally inoperable masses.

http://ift.tt/2wTUepH

Primary mediastinal paraganglioma associated with a familial variant in the succinate dehydrogenase B subunit gene

Surgical management is the mainstay of therapy for primary cardiac tumors, yet due to the rarity of these malignancies, their management and workup remains a challenge. Here, we report a unique case of a patient with a primary left ventricular cardiac paraganglioma (PGL) and describe the role of a medical genetics assessment leading to the identification of a rare variant in the SDHB gene to be the causative etiology of this cardiac tumor. Due to decreasing costs and accessibility of molecular genetic analysis, genetic testing may become an emerging diagnostic adjunct in cases of cardiac tumors.

http://ift.tt/2wTSfDi

Re: Increased expression of interleukin-23 associated with progression of colorectal cancer. Journal of Surgical Oncology 2017;115(2):208–212

http://ift.tt/2wTU6GJ

Introduction to the JSO enhanced recover after surgery seminar edition

http://ift.tt/2wU1EuY

The effect of health insurance on childhood cancer survival in the United States

BACKGROUND

The effect of health insurance on childhood cancer survival has not been well studied. Using Surveillance, Epidemiology, and End Results (SEER) data, this study was designed to assess the association between health insurance status and childhood cancer survival.

METHODS

Data on cancers diagnosed among children less than 15 years old from 2007 to 2009 were obtained from the SEER 18 registries. The effect of health insurance at diagnosis on 5-year childhood cancer mortality was estimated with marginal survival probabilities, restricted mean survival times, and Cox proportional hazards (PH) regression analyses, which were adjusted for age, sex, race/ethnicity, and county-level poverty.

RESULTS

Among 8219 childhood cancer cases, the mean survival time was 1.32 months shorter (95% confidence interval [CI], −4.31 to 1.66) after 5 years for uninsured children (n = 131) versus those with private insurance (n = 4297), whereas the mean survival time was 0.62 months shorter (95% CI, −1.46 to 0.22) for children with Medicaid at diagnosis (n = 2838). In Cox PH models, children who were uninsured had a 1.26-fold higher risk of cancer death (95% CI, 0.84-1.90) than those who were privately insured at diagnosis. The risk for those with Medicaid was similar to the risk for those with private insurance at diagnosis (hazard ratio, 1.06; 95% CI, 0.93-1.21).

CONCLUSIONS

Overall, the results suggest that cancer survival is largely similar for children with Medicaid and those with private insurance at diagnosis. Slightly inferior survival was observed for those who were uninsured in comparison with those with private insurance at diagnosis. The latter result is based on a small number of uninsured children and should be interpreted cautiously. Further study is needed to confirm and clarify the reasons for these patterns. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2eZtorI

Analysis of outcomes achieved with squamous cell carcinomas of the anus in a single university hospital over the last two decades: Clinical response rate, relapse and survival of 190 patients

Background and Objectives

We reviewed our series of anal squamous cell carcinomas (ASCC) treated over the last two decades.

Methods

ASCC patients undergoing treatment at the Leicester Royal Infirmary between 1998 and 2016 were selected. Age, gender, pathological tumor characteristics, treatment adopted, the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) at 5-year follow-up were recorded and calculated.

Results

A total of 190 ASCC were reviewed, of these 64.2% (n = 122) received primary radical chemoradiotherapy. Complete response rate was 92.6% (n = 113) and four patients with residual disease underwent a salvage APER. Twenty-eight patients experienced recurrent disease (23.0%) either systemic (n = 8), local (n = 14), or both (n = 6); six had a salvage APER. Complete follow-up data are available for 63.1% patients (77/122). Overall, the locoregional failure rate of primary chemoradiotherapy (residual + recurrent disease) was present in 29 patients (29/122; 23.8%). OS was 41.6% CSS was 69.2% and DFS 60.0% at 5 years follow-up.

Conclusions

In our series of ASCC primary chemoradiotherapy had achieved significant initial complete response rates, however, long term-follow ups still present systemic and local recurrences. APR is able to treat 30% of the pelvic recurrences (6/20), the others are either associated with systemic disease or locally inoperable masses.

http://ift.tt/2wTUepH

Primary mediastinal paraganglioma associated with a familial variant in the succinate dehydrogenase B subunit gene

Surgical management is the mainstay of therapy for primary cardiac tumors, yet due to the rarity of these malignancies, their management and workup remains a challenge. Here, we report a unique case of a patient with a primary left ventricular cardiac paraganglioma (PGL) and describe the role of a medical genetics assessment leading to the identification of a rare variant in the SDHB gene to be the causative etiology of this cardiac tumor. Due to decreasing costs and accessibility of molecular genetic analysis, genetic testing may become an emerging diagnostic adjunct in cases of cardiac tumors.

http://ift.tt/2wTSfDi

Re: Increased expression of interleukin-23 associated with progression of colorectal cancer. Journal of Surgical Oncology 2017;115(2):208–212

http://ift.tt/2wTU6GJ

Introduction to the JSO enhanced recover after surgery seminar edition

http://ift.tt/2wU1EuY

Adenocarcinoma of the lacrimal gland: a case report

Primary ductal adenocarcinomas of the lacrimal gland are very rare. This neoplasm shares some histological and immunohistochemical similarities with salivary duct carcinoma.

http://ift.tt/2eXZ4hn

Genetic variation in the Vitamin D related pathway and breast cancer risk in women of African ancestry in the Root Consortium

Abstract

The vitamin D related pathway has been evaluated in carcinogenesis but its genetic contribution remains poorly understood. We examined single-nucleotide polymorphisms (SNPs) in the vitamin D related pathway genes using data from a genome-wide association study (GWAS) of breast cancer in the African Diaspora that included 3,686 participants (1,657 cases). Pathway- and gene-level analyses were conducted using the adaptive rank truncated product test. Odds ratios (OR) and 95% confidence intervals (CI) were estimated at SNP-level. After stringent Bonferroni corrections, we observed no significant association between variants in the vitamin D pathway and breast cancer risk at the pathway-, gene-, or SNP-level. In addition, no association was found for either the reported signals from GWASs of vitamin D related traits, or the SNPs within vitamin D receptor (VDR) binding regions. Furthermore, a decrease in genetically predicted 25(OH)D levels by Mendelian randomization was not associated with breast cancer (P = 0.23). However, an association for breast cancer with the pigment synthesis/metabolism pathway almost approached significance (pathway-level P = 0.08), driven primarily by a nonsense SNP rs41302073 in TYRP1, with an OR of 1.54 (95% CI = 1.24-1.91, P_adj = 0.007). In conclusion, we found no evidence to support an association between vitamin D status and breast cancer risk in women of African ancestry, suggesting that vitamin D is unlikely to have significant effect on breast carcinogenesis. Interestingly, TYRP1 might be related to breast cancer through a non-vitamin D relevant mechanism but further studies are needed. This article is protected by copyright. All rights reserved.

http://ift.tt/2xp8bPD

Identifying actionable variants using next generation sequencing in patients with a historical diagnosis of undifferentiated pleomorphic sarcoma

Abstract

There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate the utility of next generation sequencing (NGS) in UPS to identify subsets of patients who harbour actionable mutations. Patients diagnosed with UPS underwent pathological re-evaluation by a pathologist specializing in sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons). In total, 95 patients initially classified with UPS were identified. Following pathology re-review the histological subtypes were reclassified to include: Myxofibrosarcoma (MFS, N=44); UPS(N=18); and Others (N=27; including undifferentiated spindle cell sarcoma (N=15) and dedifferentiated liposarcoma (N=6)). Seven cases were excluded from further analysis for other reasons. Baseline demographics of the finalized cohort (N=88) showed a median age of 66 years (32-95), primarily with stage I-III disease (92%) and high grade (86%) lesions. Somatic mutations were identified in 31 cases (35%)(Total mutations=36: solitary mutation(n=27); two mutations(n=3); three mutations(n=1)). The most commonly identified mutations were in TP53 (n=24), ATM (n=3) and PIK3CA (n=2). Three of 43 patients with MFS and one of 18 patients with UPS had clinically relevant mutations, mainly related to biomarkers of prediction of response, however few had targetable driver mutations. Somatic mutation status did not influence disease free or overall survival. Based on the small number of clinically relevant mutations, this data does not support the routine use of targeted NGS panels outside of research protocols in UPS. This article is protected by copyright. All rights reserved.

http://ift.tt/2gW8HtL

Breast cancer risk and germline genomic profiling of women with neurofibromatosis type 1 who developed breast cancer

Abstract

NF1 mutations predispose to neurofibromatosis type1 (NF1) and women with NF1 have a moderately elevated risk for breast cancer, especially under age 50. Germline genomic analysis may better define the risk so screening and prevention can be applied to the individuals who benefit the most. Survey conducted in several neurofibromatosis clinics in the United States has demonstrated a 17.2% lifetime risk of breast cancer in women affected with NF1. Cumulated risk to age 50 is estimated to be 9.27%. For genomic profiling, fourteen women with NF1 and a history of breast cancer were recruited and underwent whole exon sequencing (WES), targeted genomic DNA based and RNA based analysis of the NF1 gene. Deleterious NF1 pathogenic variants were identified in each woman. Frameshift mutations due to deletion/duplication/complex rearrangement were found in 50% (7/14) of the cases, nonsense mutations in 21% (3/14), in-frame splice mutations in 21% (3/14), and one case of missense mutation (7%, 1/14). No deleterious mutation was found in the following high/moderate penetrance breast cancer genes: ATM, BRCA1, BRCA2, BARD1, BRIP1, CDH1, CHEK2, FANCC, MRE11A, NBN, NF1, PALB2, PTEN, RAD50, RAD51C, TP53, and STK11. Twenty-five rare or common variants in cancer related genes were discovered and may have contributed to the breast cancers in these individuals. Breast cancer predisposition modifiers in women with NF1 may involve a great variety of molecular and cellular functions. This article is protected by copyright. All rights reserved.

http://ift.tt/2vZ4HTJ

Hepatocellular Carcinoma with Bone Metastases: Incidence, Prognostic Significance, and Management—Single-Center Experience

Abstract

Background

Hepatocellular carcinoma (HCC) represents one of the most common causes of cancer-related deaths worldwide, with rising incidence in the USA. Bone metastases with HCC, in particular, have an extremely poor prognosis. We present prevalence, treatment, and survival of patients with bone and more specifically spinal metastases from HCC.

Methods

A retrospective analysis was done at a single tertiary care institution of patients with bone metastases from HCC between January 2005 and December 2015.

Results

Among 1017 patients with HCC, 20 were found to have bone metastases of which 11 had spinal metastases. Seventeen (85%) were male, with median age of 58 years at time of HCC diagnosis. Systemic chemotherapy and sorafenib were used in 12 (60%) patients, and 12 (60%) received radiation therapy. Among patients who did not receive therapy, median survival was 76 days. Median survival after diagnosis of metastasis in patients on sorafenib and radiation were 106 and 100 days, respectively.

Conclusion

Bone metastases in HCC are very rare and aggressive. Due to its rarity, optimal treatment strategies are not well defined. Early diagnosis is important for optimal therapy and improved survival.

http://ift.tt/2xq2UXU

Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment

Summary

Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child–Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child–Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand–foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child–Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child–Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.

http://ift.tt/2xf4PxG

A review of the biologic and clinical significance of genetic mutations in angioimmunoblastic T-cell lymphoma

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, characterized by immune system-dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A), and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T-cell receptor signaling pathway in AITL. In this review, we will focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients.

This article is protected by copyright. All rights reserved.

http://ift.tt/2xn0PvS

Injection Volume and Anesthetic Effect in Serratus Plane Block.

Background and Objectives: Serratus plane block is performed for analgesia of the anterior chest wall. However, there has been no study concerning the appropriate volume for this block. This prospective randomized controlled study assesses the dermatomal spread and analgesic effects of serratus plane block. Methods: Ultrasound-guided serratus plane block was performed for breast cancer surgery. The patients were randomly assigned to receive 20 or 40 mL of 0.375% ropivacaine. The primary end point was the number of affected dermatomes as assessed by cold test and pinprick test 20 minutes after the block procedure. Secondary end points were the time until the first postoperative analgesic rescue, adverse effects, and complications. Results: The number of affected dermatomes assessed by the cold test for patients receiving 40 mL of 0.375% ropivacaine was significantly larger than that for patients receiving 20 mL (P = 0.002; 6 [5-7] vs 4 [3-4] dermatomes). Similarly, with the pinprick test, the affected area was larger for the 40 mL group than for the 20 mL group (P = 0.009; 4 [2-6] vs 2 [1-3] dermatomes). There were no differences between the 2 groups in secondary end points. Conclusions: Ultrasound-guided serratus plane block spread in the craniocaudal direction is more widespread with 40 mL than with 20 mL of 0.375% ropivacaine. The time until the first postoperative analgesic rescue dose was not extended by a larger volume of injection. Clinical Trials Registration: UMIN Clinical Trials Registry (identifier UMIN000016549). Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

http://ift.tt/2wifvYj

Cancers, Vol. 9, Pages 121: The PI3Kδ Inhibitor Idelalisib Inhibits Homing in an in Vitro and in Vivo Model of B ALL

Cancers, Vol. 9, Pages 121: The PI3Kδ Inhibitor Idelalisib Inhibits Homing in an in Vitro and in Vivo Model of B ALL

Cancers doi: 10.3390/cancers9090121

Authors: Etai Adam Hye Na Kim Eun Ji Gang Caitlin Schnair Solomon Lee Solah Lee Sajad Khazal Osanna Kosoyan Marina Konopleva Chintan Parekh Deepa Bhojwani Alan S. Wayne Hisham Abdel-Azim Nora Heisterkamp Yong-Mi Kim

The quest continues for targeted therapies to reduce the morbidity of chemotherapy and to improve the response of resistant leukemia. Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stromal cells triggers intracellular signals that promote cell-adhesion-mediated drug resistance (CAM-DR). Idelalisib, an U.S. Food and Drug Administration (FDA)-approved PI3Kδ-specific inhibitor has been shown to be effective in CLL in down-regulating p-Akt and prolonging survival in combination with Rituximab; herein we explore the possibility of its use in B ALL and probe the mechanism of action. Primary B ALL in contact with OP9 stromal cells showed increased p-Aktser473. Idelalisib decreased p-Akt in patient samples of ALL with diverse genetic lesions. Addition of idelalisib to vincristine inhibited proliferation when compared to vincristine monotherapy in a subset of samples tested. Idelalisib inhibited ALL migration to SDF-1α in vitro and blocked homing of ALL cells to the bone marrow in vivo. This report tests PI3Kδ inhibitors in a more diverse group of ALL than has been previously reported and is the first published report of idelalisib inhibiting homing of ALL cells to bone marrow. Our data support further pre-clinical evaluation of idelalisib for the therapy of B ALL.

http://ift.tt/2jcLIig

Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project.

BACKGROUND: Mechanistic aspects of cognitive recovery after anesthesia and surgery are not yet well characterized, but may be vital to distinguishing the contributions of anesthesia and surgery in cognitive complications common in the elderly such as delirium and postoperative cognitive dysfunction. This article describes the aims and methodological approach to the ongoing study, Trajectory of Recovery in the Elderly (TORIE), which focuses on the trajectory of cognitive recovery from general anesthesia. METHODS: The study design employs cognitive testing coupled with neuroimaging techniques such as functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labeling to characterize cognitive recovery from anesthesia and its biological correlates. Applying these techniques to a cohort of age-specified healthy volunteers 40-80 years of age, who are exposed to general anesthesia alone, in the absence of surgery, will assess cognitive and functional neural network recovery after anesthesia. Imaging data are acquired before, during, and immediately after anesthesia, as well as 1 and 7 days after. Detailed cognitive data are captured at the same time points as well as 30 days after anesthesia, and brief cognitive assessments are repeated at 6 and 12 months after anesthesia. RESULTS: The study is underway. Our primary hypothesis is that older adults may require significantly longer to achieve cognitive recovery, measured by Postoperative Quality of Recovery Scale cognitive domain, than younger adults in the immediate postanesthesia period, but all will fully recover to baseline levels within 30 days of anesthesia exposure. Imaging data will address systems neuroscience correlates of cognitive recovery from general anesthesia. CONCLUSIONS: The data acquired in this project will have both clinical and theoretical relevance regardless of the outcome by delineating the mechanism behind short-term recovery across the adult age lifespan, which will have major implications for our understanding of the effects of anesthetic drugs. (C) 2017 International Anesthesia Research Society

http://ift.tt/2vNmVn4

Postoperative Complications Affecting Survival After Cardiac Arrest in General Surgery Patients.

BACKGROUND: Postoperative cardiac arrest is uncommon but associated with a high mortality risk in general surgery patients and is often preceded by postoperative complications. The relationships between previous complications and mortality after cardiac arrest in general surgery patients have not been completely evaluated. METHODS: retrospective, observational cohort of general surgery in patients with cardiac arrest occurring after postoperative day (POD) #0 (and up to POD #30) was obtained from the 2012-2013 American College of Surgeons National Surgical Quality Improvement Program. Previous complication was defined as at least one of the following occurring before the POD of cardiac arrest: (1) acute kidney injury; (2) acute respiratory failure; (3) deep vein thrombosis/pulmonary embolus; (4) myocardial infarction; (5) sepsis/septic shock; (6) stroke; and/or (7) transfusion. The associations between previous complications and mortality after cardiac arrest were assessed using Cox proportional hazards models that adjusted for preoperative risk factors. RESULTS: Of 1352 patients with postoperative cardiac arrest, 746 patients (55%) developed at least 1 complication before cardiac arrest. Overall 30-day mortality was 71% (958/1352) and was similar among patients with and without a previous complication (71% [533/746] vs 70% [425/606]; P = .60). Patients with previous complications did not have an increased risk of mortality, compared to patients without previous complications, in adjusted Cox models (hazard ratio, 1.03; 95% confidence interval, 0.90-1.18; P = .70). In addition, no previous complication was associated with increased mortality risk in individual analyses. CONCLUSIONS: Among general surgery patients with cardiac arrest after POD #0, complications occurring before cardiac arrest are common but are not associated with increased mortality risk. (C) 2017 International Anesthesia Research Society

http://ift.tt/2gTsM7B

The Assignment of American Society of Anesthesiologists Physical Status Classification for Adult Polytrauma Patients: Results From a Survey and Future Considerations.

BACKGROUND: The American Society of Anesthesiologists (ASA) physical status (PS) classification system assesses the preoperative health of patients. Previous studies demonstrated poor interrater reliability and variable ASA PS scores, especially in trauma scenarios. There are few studies that evaluated the assignment of ASA PS scores in trauma patients and no studies that evaluated ASA PS assignment in severely injured adult polytrauma patients. Our objective was to assess interrater reliability and identify sources of discrepancy among anesthesiologists and trauma surgeons in designating ASA PS scores to adult polytrauma patients. METHODS: A link to an online survey containing questions assessing attitudes regarding ASA PS classification, demographic information, and 8 fictional trauma cases was e-mailed to anesthesiologists and trauma surgeons. The participants were asked to assign an ASA PS score to each scenario and explain their choice. Rater-versus-reference and interrater reliability, beyond that expected by chance, among respondents was analyzed using the Fleiss kappa analysis. RESULTS: A total of 349 participants completed the survey. All 8 cases had inconsistent ASA PS scores; several cases had scores ranging from I to VI and variable emergency (E) designations. Using weighted kappa (Kw) analysis for a subset of 201 respondents (101 trauma surgeons [S] and 100 anesthesiologists [A]), we found moderate (Kw = 0.63; SE = 0.024; 95% confidence interval, 0.594-0.666; P

http://ift.tt/2vMKYSX

Radiofrequency Treatments on the Spine, 1st ed.

No abstract available

http://ift.tt/2gSPSvc

Descriptive Statistics: Reporting the Answers to the 5 Basic Questions of Who, What, Why, When, Where, and a Sixth, So What?.

Descriptive statistics are specific methods basically used to calculate, describe, and summarize collected research data in a logical, meaningful, and efficient way. Descriptive statistics are reported numerically in the manuscript text and/or in its tables, or graphically in its figures. This basic statistical tutorial discusses a series of fundamental concepts about descriptive statistics and their reporting. The mean, median, and mode are 3 measures of the center or central tendency of a set of data. In addition to a measure of its central tendency (mean, median, or mode), another important characteristic of a research data set is its variability or dispersion (ie, spread). In simplest terms, variability is how much the individual recorded scores or observed values differ from one another. The range, standard deviation, and interquartile range are 3 measures of variability or dispersion. The standard deviation is typically reported for a mean, and the interquartile range for a median. Testing for statistical significance, along with calculating the observed treatment effect (or the strength of the association between an exposure and an outcome), and generating a corresponding confidence interval are 3 tools commonly used by researchers (and their collaborating biostatistician or epidemiologist) to validly make inferences and more generalized conclusions from their collected data and descriptive statistics. A number of journals, including Anesthesia & Analgesia, strongly encourage or require the reporting of pertinent confidence intervals. A confidence interval can be calculated for virtually any variable or outcome measure in an experimental, quasi-experimental, or observational research study design. Generally speaking, in a clinical trial, the confidence interval is the range of values within which the true treatment effect in the population likely resides. In an observational study, the confidence interval is the range of values within which the true strength of the association between the exposure and the outcome (eg, the risk ratio or odds ratio) in the population likely resides. There are many possible ways to graphically display or illustrate different types of data. While there is often latitude as to the choice of format, ultimately, the simplest and most comprehensible format is preferred. Common examples include a histogram, bar chart, line chart or line graph, pie chart, scatterplot, and box-and-whisker plot. Valid and reliable descriptive statistics can answer basic yet important questions about a research data set, namely: "Who, What, Why, When, Where, How, How Much?" (C) 2017 International Anesthesia Research Society

http://ift.tt/2vNKFHu