Perioperative management of patients with cancer pain treated with opioids: a retrospective study

Abstract

Purpose

We retrospectively studied perioperative management of patients receiving opioid treatment for cancer pain to facilitate establishing a standard policy for our institute.

Methods

Subjects were patients who had been administered strong opioids for cancer pain and had undergone surgery with general anesthesia. We divided the patients into groups C and D. Group C was comprised of patients who had been administered their baseline opioids continuously during the perioperative period, and group D of those who had discontinued baseline opioid use during this period.

Results

We identified 70 evaluable patients, 36 in group C and 34 in group D. The intraoperative anesthesia courses were similar, being uneventful, in all cases. With respect to postoperative adverse effects within 24 h after awakening from anesthesia, severe adverse effects (additional administration of more than four analgesics and intense agitation) were significantly more frequent in group D than in group C (12 vs 1, respectively. p = 0.004). Univariate analysis revealed that baseline opioid discontinuation was the only factor associated with severe adverse effects [odds ratio 12.6, 95% confidence interval (1.49–105.8), p = 0.01].

Conclusion

Discontinuation of baseline opioid increased adverse effects in the early postoperative period, which were attributed to exacerbation of early postoperative pain.

https://ift.tt/2xMtprC

Predictors, utilization patterns, and overall survival of patients undergoing metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy

Publication date: Available online 5 June 2018
Source:European Journal of Surgical Oncology
Author(s): Maxine Sun, Christian P. Meyer, Jose A. Karam, Guillermo de Velasco, Steven L. Chang, Sumanta K. Pal, Quoc-Dien Trinh, Toni K. Choueiri
IntroductionMetastasectomy (MSX) is considered a treatment option in patients with metastatic renal cell carcinoma (mRCC) at diagnosis, but its role in the targeted therapy era is unclear. We sought to describe the utilization trends of MSX and survival outcomes in a large US cohort.Materials and MethodsUsing the National Cancer Database, we identified patients undergoing MSX for mRCC at diagnosis between 2006-2013. Linear regression methods estimated utilization trends, and hierarchical models identified independent predictors of MSX after adjusting for hospital clustering. Kaplan-Meier survival estimates and Cox proportional hazard models were used to evaluate overall survival according to treatment after propensity-score matching.ResultsOf 6994 mRCC patients, 1976 underwent MSX (28.3%). Those treated at academic facilities were more likely to undergo a MSX (OR: 1.57, 95% CI 1.20-2.06, p=0.001). In contrast, older patients (OR: 0.99, 95% CI: 0.98-1.00), black race (OR: 0.65, 95% CI: 0.51-0.82), higher pT stage (OR: 0.76, 95% CI: 0.65-0.89), and who received targeted therapy (OR: 0.72, 95% CI: 0.63-0.82, all p≤0.008) were less likely to undergo MSX. Overall, MSX patients had an improved survival compared to non-MSX patients (HR: 0.83, 95% CI: 0.77-0.90, p<0.001), as well as among patients treated with targeted therapy (HR: 0.77, 95% CI: 0.77-0.96, p=0.008).ConclusionsOur findings indicate that MSX-treated patients may benefit from an improved overall survival compared to non-MSX treated patients. Good patient selection and a proper risk stratification strategy are still very important considerations.



https://ift.tt/2Jhh7wA

Relationship between complications and long-term prognosis after total gastrectomy with splenectomy for proximal advanced gastric cancer

Publication date: Available online 5 June 2018
Source:European Journal of Surgical Oncology
Author(s): Bing Quan, Wen-Tao Yan, Jiong-Jie Yu, Feng Shen, Tian Yang




https://ift.tt/2sL2aIb

Molecular targets of celastrol in cancer: Recent trends and advancements

Publication date: Available online 5 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Dharambir Kashyap, Ajay Sharma, Hardeep Singh Tuli, Katrin Sak, Tapan Mukherjee, Anupam Bishayee
Despite the advancement in the well-equipped and sophisticated laboratories and facilities, cancer remains to be a major cause of death worldwide. Consequently, further investigation of novel strategies need to be evolved. Since the last few decades, the utilization of phytochemicals is emerging against several human cancers, including lung, breast, colon carcinoma, lymphoma, and other hematological malignancies. Terpenoids are a category of therapeutically active phytochemicals that have been utilized against cancer, cardiovascular and neurodegenerative disorders. Particularly, celastrol, a pentacyclic terpenoid, is well-studied for its variety of pharmacological properties. It is well documented that celastrol can modulate a variety of signaling pathways. Celastrol's anti-proliferative role has been found to be associated with its pro-apoptotic (via protein kinase B), anti-angiogenic (via vascular endothelial growth factor and vascular endothelial growth factor receptor), anti-metastatic (via matrix metalloproteinases), and anti-inflammatory (via cytokines and chemokines) activities. This review describes various molecular mechanisms of celastrol for understanding the biology of cancer initiation, progression as well as designing efficacious therapeutic strategies.



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The Canonical Wnt Pathway Drives Macropinocytosis in Cancer

Macropinocytosis has emerged as an important pathway of protein acquisition in cancer cells, particularly in tumors with activated Ras such as pancreatic and colon cancer. Macropinocytosis is also the route of entry of Bacillus Calmette-Guerin (BCG) and other microbial therapies of cancer. Despite this important role in tumor biology and therapy, the full mechanisms by which cancer cells can activate macropinocytosis remain incompletely defined. Using BCG uptake to assay macropinocytosis, we executed a genome-wide shRNA screen for macropinocytosis activators and identified Wnt pathway activation as a strong driver of macropinocytosis. Wnt-driven macropinocytosis was downstream of the beta catenin-dependent canonical Wnt pathway, was Pak1 dependent, and supported albumin-dependent growth in Ras-WT cells. In cells with activated Ras-dependent macropinocytosis, pharmacologic or genetic inhibition of Wnt signaling suppressed macropinocytosis. In a mouse model of Wnt-driven colonic hyperplasia via APC silencing, Wnt-activated macropinocytosis stimulated uptake of luminal microbiota, a process reversed by topical pharmacologic inhibition of macropinocytosis. Our findings indicate that Wnt pathway activation drives macropinocytosis in cancer, and its inhibition could provide a therapeutic vulnerability in Wnt-driven intestinal polyposis and cancers with Wnt activation.

https://ift.tt/2M3fQHs

Kras and Tp53 mutations cause cholangiocyte- and hepatocyte-derived cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a primary liver cancer epidemiologically linked with liver injury which has poorly understood incipient stages and lacks early diagnostics and effective therapies. While iCCA is conventionally thought to arise from the biliary tract, studies have suggested that both hepatocytes and biliary cells (cholangiocytes) may give rise to iCCA. Consistent with the plasticity of these cell lineages, primary liver carcinomas exhibit a phenotypic range from hepatocellular carcinoma (HCC) to iCCA with intermediates along this spectrum. Here we generated mouse models to examine the consequence of targeting mutant Kras and Tp53, common alterations in human iCCA, to different adult liver cell types. Selective induction of these mutations in the SOX9+ population, predominantly of mature cholangiocytes, resulted in iCCA emerging from premalignant biliary intraepithelial neoplasia (BillN). By contrast, adult hepatocytes were relatively refractory to these mutations and formed rare hepatocellular carcinomas (HCC). In this context, injury accelerated hepatocyte-derived tumorigenesis and promoted a phenotypic switch to iCCA. BilIN precursor lesions were absent in the hepatocyte-derived iCCA models, pointing towards distinct and direct emergence of a malignant cholangiocytic phenotype from injured, oncogenically primed hepatocytes. Tp53 loss enhanced reprogramming of hepatocytes to biliary cells, which may represent a mechanism facilitating formation of hepatocyte-derived iCCA. Overall, our work shows iCCA driven by Kras and Tp53 may originate from both mature cholangiocytes and hepatocytes, and factors such as chronic liver injury and underlying genetic mutations determine the path of progression and resulting cancer phenotype.

https://ift.tt/2xLxegC

Oncogenic properties of NEAT1 in prostate cancer cells depend on the CDC5L-AGRN transcriptional regulation circuit

The long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been shown to regulate multiple cancer-related cellular activities including cell proliferation, apoptosis, and migration. In this study, we confirm that repression of NEAT1 induces DNA damage, disturbs the cell cycle, and arrests the proliferation of prostate cancer cells. By taking advantage of the prostate cancer tumor transcriptome profiles from The Cancer Genome Atlas (TCGA), our data-mining pipeline identified a series of transcription factors (TF) whose regulatory activities on target genes depended on the level of NEAT1. Among them was putative TF CDC5L, which bound directly to NEAT1. Silencing NEAT1 in prostate cancer cells repressed the transcriptional activity of CDC5L, and RNA-seq and ChIP-seq analyses further revealed a handful of potential targets of CDC5L regulated by NEAT1 expression. One target of CDC5L, ARGN, mediated the strong phenotypic consequences of NEAT1 reduction, including DNA damage, cell cycle dysregulation, and proliferation arrest. In summary, we have established the requirement of the CDC5L-AGRN circuit for the essential oncogenic role of NEAT1 in prostate cancer cells.

https://ift.tt/2M3fQaq

TCIApathfinder: an R client for The Cancer Imaging Archive REST API

The Cancer Imaging Archive (TCIA) hosts publicly available de-identified medical images of cancer from over 25 body sites and over 30,000 patients. Over 400 published studies have utilized freely available TCIA images. Images and metadata are available for download through a web interface or a REST API. Here we present TCIApathfinder, an R client for the TCIA REST API. TCIApathfinder wraps API access in user-friendly R functions that can be called interactively within an R session or easily incorporated into scripts. Functions are provided to explore the contents of the large database and to download image files. TCIApathfinder provides easy access to TCIA resources in the highly popular R programming environment. TCIApathfinder is freely available under the MIT license as a package on CRAN (https://ift.tt/2Cu0Td1) and at https://ift.tt/2Cu0TK3.

https://ift.tt/2JhxPIs

Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people

Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people

Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people, Published online: 06 June 2018; doi:10.1038/s41416-018-0124-8

Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people

https://ift.tt/2kQdVcM

Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome

Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome

Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a <i>BRAF</i>-mutant subset with high CA 19-9 level and poor outcome, Published online: 06 June 2018; doi:10.1038/s41416-018-0115-9

Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome

https://ift.tt/2HmLHzk

Efficacy of a docetaxel-5FU-oxaliplatin regimen (TEFOX) in first-line treatment of advanced gastric signet ring cell carcinoma: an AGEO multicentre study

Efficacy of a docetaxel-5FU-oxaliplatin regimen (TEFOX) in first-line treatment of advanced gastric signet ring cell carcinoma: an AGEO multicentre study

Efficacy of a docetaxel-5FU-oxaliplatin regimen (TEFOX) in first-line treatment of advanced gastric signet ring cell carcinoma: an AGEO multicentre study, Published online: 06 June 2018; doi:10.1038/s41416-018-0133-7

Efficacy of a docetaxel-5FU-oxaliplatin regimen (TEFOX) in first-line treatment of advanced gastric signet ring cell carcinoma: an AGEO multicentre study

https://ift.tt/2sJG5cT

Body mass index (BMI) trajectories and risk of colorectal cancer in the PLCO cohort

Body mass index (BMI) trajectories and risk of colorectal cancer in the PLCO cohort

Body mass index (BMI) trajectories and risk of colorectal cancer in the PLCO cohort, Published online: 06 June 2018; doi:10.1038/s41416-018-0121-y

Body mass index (BMI) trajectories and risk of colorectal cancer in the PLCO cohort

https://ift.tt/2kP6F0T

Agrin has a pathological role in the progression of oral cancer

Agrin has a pathological role in the progression of oral cancer

Agrin has a pathological role in the progression of oral cancer, Published online: 06 June 2018; doi:10.1038/s41416-018-0135-5

Agrin has a pathological role in the progression of oral cancer

https://ift.tt/2kPQy2Z

Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer

Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer

Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer, Published online: 06 June 2018; doi:10.1038/s41416-018-0089-7

Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer

https://ift.tt/2Hkkb5v

Multimodality Treatment of Desmoplastic small round cell tumor: Chemotherapy and Complete Cytoreductive Surgery Improve Patient Survival

Purpose Desmoplastic small round cell tumor (DSRCT), which harbors EWSR1-WT1 t(11;22)(p13:q12) chromosomal translocation, is an aggressive malignancy that typically presents as intra-abdominal sarcomatosis in young males. Given its rarity, optimal treatment has not been defined. Experimental Design We conducted a retrospective study of 187 DSRCT patients treated at MD Anderson Cancer Center over two decades. Univariate and multivariate regression analyses were performed. We determined whether chemotherapy, complete cytoreductive surgery (CCS), hyperthermic intraperitoneal cisplatin (HIPEC), and/or whole abdominal radiation (WART) improve overall survival in DSRCT patients. Critically, since our institutional practice limits HIPEC and WART to patients with less extensive, potentially resectable disease that had benefited from neoadjuvant chemotherapy, a time-variant analysis was performed to evaluate those adjunct treatment modalities. CONCLUSIONS Improved 3- and 5-year overall survival were observed following multidisciplinary treatment that includes ES-based chemotherapy and complete tumor cytoreductive surgery, but few if any patients are cured. Prospective randomized studies will be required to prove whether HIPEC or WART are important. In the meantime, chemotherapy and CCS remain the cornerstone of treatment and provide a solid foundation to evaluate new biologically targeted therapies.

https://ift.tt/2xHUgoG

Immunotherapy of Primary Brain Tumors: Facts and Hopes

The field of cancer immunotherapy has made exciting progress for some cancer types in recent years. However, recent failures of late phase clinical trials evaluating checkpoint blockade in glioblastoma (GBM) patients represent continued challenges for brain cancer immunotherapy. This is likely due to multiple factors, including but not limited to marked genetic and antigenic heterogeneity, relatively low mutational loads and paucity of GBM-infiltrating T cells. We review recent and ongoing studies targeting the checkpoint molecules as monotherapy or in combination with other modalities, and discuss the mechanisms underlying the unresponsiveness of GBM to single modality immunotherapy approaches. We also discuss other novel immunotherapy approaches that may promote T cell responses and overcome the "cold tumor" status of GBM, including oncolytic viruses and adoptive T cell therapy.

https://ift.tt/2LZb9hM

Identification of a Genomic Region Between SLC29A1 and HSP90AB1 Associated with Risk of Bevacizumab-Induced Hypertension: CALGB 80405 (Alliance)

Purpose: Bevacizumab is a VEGF-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of multiple cancers. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy or lead to cardiovascular complications. The factors that contribute to interindividual variability in blood pressure rise during bevacizumab treatment are not well understood. Experimental Design: To identify genomic regions associated with bevacizumab-induced hypertension risk, sequencing of candidate genes and flanking regulatory regions was performed on 61 bevacizumab-treated patients (19 cases developed early-onset grade 3 hypertension and 42 controls had no reported hypertension in the first six cycles of treatment). SNP-based tests for common variant associations and gene-based tests for rare variant associations were performed in 174 candidate genes. Results: Four common variants in independent linkage disequilibrium blocks between SLC29A1 and HSP90AB1 were among the top associations. Validation in larger bevacizumab-treated cohorts supported association between rs9381299 with early grade 3+ hypertension (P = 0.01, OR 2.4) and systolic blood pressure > 180 mmHg (P = 0.02, OR 2.1). rs834576 was associated with early grade 3+ hypertension in CALGB 40502 (P = 0.03, OR 2.9). These SNP regions are enriched for regulatory elements that may potentially increase gene expression. In vitro overexpression of SLC29A1 in human endothelial cells disrupted adenosine signaling and reduced nitric oxide levels that were further lowered upon bevacizumab exposure. Conclusions: The genomic region between SLC29A1 and HSP90AB1 and its role in regulating adenosine signaling are key targets for further investigation into the pathogenesis of bevacizumab-induced hypertension.

https://ift.tt/2Joa3KD

PARP inhibitors in ovarian cancer: a trailblazing and transformative journey

PARP inhibitors have transformed treatment for ovarian cancer, a cancer notable for homologous recombination (HR) deficiencies and aberrant DNA repair, especially high grade serous subtype. PARP inhibitors are now approved for recurrent ovarian cancer as maintenance following response to platinum chemotherapy and BRCA mutated (BRCAm) cancer treatment.

https://ift.tt/2M1ept5

ECT: a new look at an old friend

Purpose of review Electroconvulsive therapy (ECT) as a treatment option in psychiatry is advancing day by day. This review discusses new advancements in ECT with regards to anesthetic variables, stimulus, and response variables along with their impact on clinical outcomes. Recent findings Anesthetic variables influence clinical efficacy and patient tolerance of ECT. Although etomidate or a ketamine–propofol combination may be the first choice for many clinicians, the search for ideal induction agent continues. Dexmedetomidine, remifentanil, or ketamine may aid in augmentation of ECT; however, they are not recommended routinely. A systematic procedure for hyperventilation of the patient has been shown to have clinical repercussions. Optimizing anesthesia-ECT time interval (ASTI) has a significant impact on the success of the procedure. BIS monitoring alone cannot be relied upon for timing stimulus. High-dose brief pulse right unilateral ECT represents an acceptable first-line form of treatment, though there is currently no 'gold standard'. Other stimulus variations such as focal electrically administered seizure therapy, individualized low-amplitude seizure therapy, magnetic seizure therapy, left unilateral and left anterior right temporal electrode placements are explored to reduce memory effects. EEG ictal indices may be relied upon for seizure adequacy, and therefore may be used to both guide treatment and predict the outcome of the procedure. Summary Modern ECT is streamlined by augmentation with drugs, hyperventilation, optimizing anesthesia-ECT time interval, and various stimulus parameters guided by seizure adequacy markers. Correspondence to Pavan Kumar Kadiyala, Assistant Professor, Department of Psychiatry, ASR Academy of Medical Sciences, Eluru, AP 534005, India. Tel: +919980731234; e-mail: drkadiyala2@gmail.com Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2M0gENn

Do we really need an anesthesiologist for routine colonoscopy in American Society of Anesthesiologist 1 and 2 patients?

Purpose of review In an era where healthcare costs are being heavily scrutinized, every expenditure is reviewed for medical necessity. Multiple national gastroenterology societies have issued statements regarding whether an anesthesiologist is necessary for routine colonoscopies in American Society of Anesthesiologist (ASA) 1 and 2 patients. Recent findings A large percentage of patients are undergoing screening colonoscopy without any sedation at all, which would not require an independent practitioner to administer medications. Advances in technique and technology are making colonoscopies less stimulating. Advantages to administering sedation, including propofol, have been seen even when not administered under the direction of an anesthesiologist and complications seem to be rare. The additional cost of having monitored anesthesia care appears to be a driving factor in whether a patient receives it or not. Summary A large multiinstitutional randomized control trial would be necessary to rule out potential confounders and to determine whether there is a safety benefit or detriment to having anesthesiologist-directed care in the setting of routine colonoscopies in ASA 1 and 2 patients. Further discussion would be necessary regarding what the monetary value of that effect is if a small difference were to be detected. Correspondence to Jeffrey D. White, MD, Department of Anesthesiology, University of Florida College of Medicine, 1600 SW Archer Road, PO Box 100254, Gainesville, FL 32610, USA. Tel: +1 352 273 6575; e-mail: jwhite@anest.ufl.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2xKXSGJ

Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people

https://ift.tt/2HoeB1Y

Agrin has a pathological role in the progression of oral cancer

https://ift.tt/2kRFdzs

Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome

https://ift.tt/2sJGa0b

Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer

https://ift.tt/2sA9kjd

Body mass index (BMI) trajectories and risk of colorectal cancer in the PLCO cohort

https://ift.tt/2sG9h4J

Efficacy of a docetaxel-5FU-oxaliplatin regimen (TEFOX) in first-line treatment of advanced gastric signet ring cell carcinoma: an AGEO multicentre study

https://ift.tt/2kPQmAN

Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists

Background Over the past 2 decades, the use of intravenous ketamine infusions as a treatment for chronic pain has increased dramatically, with wide variation in patient selection, dosing, and monitoring. This has led to a chorus of calls from various sources for the development of consensus guidelines. Methods In November 2016, the charge for developing consensus guidelines was approved by the boards of directors of the American Society of Regional Anesthesia and Pain Medicine and, shortly thereafter, the American Academy of Pain Medicine. In late 2017, the completed document was sent to the American Society of Anesthesiologists' Committees on Pain Medicine and Standards and Practice Parameters, after which additional modifications were made. Panel members were selected by the committee chair and both boards of directors based on their expertise in evaluating clinical trials, past research experience, and clinical experience in developing protocols and treating patients with ketamine. Questions were developed and refined by the committee, and the groups responsible for addressing each question consisted of modules composed of 3 to 5 panel members in addition to the committee chair. Once a preliminary consensus was achieved, sections were sent to the entire panel, and further revisions were made. In addition to consensus guidelines, a comprehensive narrative review was performed, which formed part of the basis for guidelines. Results Guidelines were prepared for the following areas: indications; contraindications; whether there was evidence for a dose-response relationship, or a minimum or therapeutic dose range; whether oral ketamine or another N-methyl-D-aspartate receptor antagonist was a reasonable treatment option as a follow-up to infusions; preinfusion testing requirements; settings and personnel necessary to administer and monitor treatment; the use of preemptive and rescue medications to address adverse effects; and what constitutes a positive treatment response. The group was able to reach consensus on all questions. Conclusions Evidence supports the use of ketamine for chronic pain, but the level of evidence varies by condition and dose range. Most studies evaluating the efficacy of ketamine were small and uncontrolled and were either unblinded or ineffectively blinded. Adverse effects were few and the rate of serious adverse effects was similar to placebo in most studies, with higher dosages and more frequent infusions associated with greater risks. Larger studies, evaluating a wider variety of conditions, are needed to better quantify efficacy, improve patient selection, refine the therapeutic dose range, determine the effectiveness of nonintravenous ketamine alternatives, and develop a greater understanding of the long-term risks of repeated treatments. Accepted for publication March 17, 2018. Address correspondence to: Steven P. Cohen, MD, 550 N Broadway, Suite 301 Baltimore, MD 21029 (e-mail: scohen40@jhmi.edu). Accepted for publication March 17, 2018. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army or the Department of Defense. Because this document has neither been presented to nor approved by either the American Society of Anesthesiologists Board of Directors or House of Delegates, it is not an official or approved statement or policy of the Society. Variances from the recommendations contained in the document may be acceptable based on the judgment of the responsible anesthesiologist. S.P.C. is funded in part by a Congressional Grant from the Center for Rehabilitation Sciences Research, Uniformed Services University of the Health Sciences, Bethesda, MD (SAP grant 111726), which also paid for Open Access publication. The authors declare no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

https://ift.tt/2Llv35t

Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists

Background Ketamine infusions have been used for decades to treat acute pain, but a recent surge in usage has made the infusions a mainstay of treatment in emergency departments, in the perioperative period in individuals with refractory pain, and in opioid-tolerant patients. The widespread variability in patient selection, treatment parameters, and monitoring indicates a need for the creation of consensus guidelines. Methods The development of acute pain ketamine guidelines grew as a corollary from the genesis of chronic pain ketamine guidelines. The charge for the development of acute pain ketamine guidelines was provided by the Boards of Directors of both the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine, who approved the document along with the American Society of Anesthesiologists' Committees on Pain Medicine and Standards and Practice Parameters. The committee chair developed questions based on input from the committee during conference calls, which the committee then refined. Groups of 3 to 5 panel members and the committee chair were responsible for answering individual questions. After preliminary consensus was achieved, the entire committee made further revisions via e-mail and conference calls. Results Consensus guidelines were prepared in the following areas: indications, contraindications for acute pain and whether they differ from those for chronic pain, the evidence for the use of ketamine as an adjunct to opioid-based therapy, the evidence supporting patient-controlled ketamine analgesia, the use of nonparenteral forms of ketamine, and the subanesthetic dosage range and whether the evidence supports those dosages for acute pain. The group was able to reach consensus on the answers to all questions. Conclusions Evidence supports the use of ketamine for acute pain in a variety of contexts, including as a stand-alone treatment, as an adjunct to opioids, and, to a lesser extent, as an intranasal formulation. Contraindications for acute pain are similar to those for chronic pain, partly based on the observation that the dosage ranges are similar. Larger studies evaluating different acute pain conditions are needed to enhance patient selection, determine the effectiveness of nonparenteral ketamine alternatives, define optimal treatment parameters, and develop protocols optimizing safety and access to care. Accepted for publication March 7, 2018. Address correspondence to: Steven P. Cohen, MD, 550 N Broadway, Suite 301, Baltimore, MD 21029 (e-mail: scohen40@jhmi.edu). S.P.C. is funded in part by a Congressional grant from the Center for Rehabilitation Sciences Research, Uniformed Services University of the Health Sciences, Bethesda, MD (SAP grant 111726). The authors declare no conflict of interest. The opinions or assertions contained herein are those of the authors, the American Society of Regional Anesthesia and Pain Medicine, and the American Academy of Pain Medicine and do not necessarily reflect the views of the Department of the Army or the Department of Defense. Because this document has neither been presented to nor approved by either the ASA Board of Directors or House of Delegates, it is not an official or approved statement or policy of the Society. Variances from the recommendations contained in the document may be acceptable based on the judgment of the responsible anesthesiologist. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

https://ift.tt/2Jt3VUJ

Toxin-Based Drug Moxetumomab Pasudotox May Be New Option for Rare Leukemia

People diagnosed with hairy cell leukemia (HCL) may have an effective new treatment option, a type of drug called an immunotoxin. Read more about how this treatment, moxetumomab pasudotox, faired in a phase 3 clinical trial in patients with advanced HCL.

https://ift.tt/2JdqHRt

Scleromalacia perforans: a case report

Scleromalacia perforans is a rare ocular manifestation of rheumatoid arthritis which can potentially lead to blindness and is a late consequence in the course of the disease. It is an unusual finding for it to...

https://ift.tt/2JdwK8y

Evaluation of gold fiducial marker manual localisation for magnetic resonance-only prostate radiotherapy

The use of intraprostatic gold fiducial markers (FMs) ensures highly accurate and precise image-guided radiation therapy for patients diagnosed with prostate cancer thanks to the ease of localising FMs on phot...

https://ift.tt/2JkpymQ

Carotid artery infusion via implantable catheters for squamous cell carcinoma of the tonsils

Abstract

Background

Chemoradiotherapy has a dominant role in therapy for head and neck cancers. However, impressive results are often disturbed by adverse events such as dysphagia, xerostomia, and functional speech and hearing loss. To avoid exceeding toxicity limits in patients with primary and recurrent cancers of the tonsils, chemotherapy was administered intra-arterially via implantable Jet-Port-Allround catheters.

Methods

We report on patients with primary and recurrent cancers of the tonsils. Eleven patients who refused chemoradiation were included in this trial. Of the seven patients without prior therapy, one was stage I, one was stage III, three were stage IVA, one was stage IVB, and one was stage IVC. The four patients who were in progression after prior chemoradiation were stage IVA. The median follow-up time was 47 months (20 to 125 months).

After the implantation of a Jet-Port-Allround catheter into the carotid artery, the patients received intra-arterial infusion chemotherapy with venous chemofiltration for systemic detoxification. The stage I patient received lower-dose chemotherapy without chemofiltration. The stage IVC patient with lung metastases and a primary tumor that extended across the midline to the contralateral tonsil received additional isolated thoracic perfusion chemotherapy.

Results

All seven chemoradiation-naïve patients exhibited clinically complete responses and are still alive after 20 to 125 months. Among the four patients who had relapsed after prior chemoradiation, the intra-arterial therapy elicited only poor responses, and the median survival time was 7.5 months. After carotid artery infusion chemotherapy, none of the patients required tube feeding. No cases of dysphagia, xerostomia, or functional speech and hearing loss have been reported among the patients without prior chemoradiotherapy.

Conclusion

Despite the administration of low total dosages, intra-arterial infusion generates high concentrations of chemotherapeutics. In combination with chemofiltration, the systemic toxicity is kept within acceptable limits. Among the non-pretreated patients, better tumor responses and long-term tumor control were noted compared with those who had prior chemoradiation. Implantable Jet-Port-Allround carotid artery catheters facilitate the application of regional chemotherapy.

https://ift.tt/2LmPHSI

Therapeutic effects of oxaliplatin-based neoadjuvant chemotherapy and chemoradiotherapy in patients with locally advanced rectal cancer: a single-center, retrospective cohort study

Abstract

Background

Neoadjuvant chemoradiotherapy (NACRT) has now become the standard treatment for locally advanced rectal cancer (LARC). NACRT has decreased local relapse (LR) rate in patients with LARC; however, distant relapse has recently attracted much attention. This study aimed to assess the feasibility and efficiency of neoadjuvant chemotherapy (NAC) for LARC.

Methods

Data on patients with cT3/4 and N+ rectal cancer who were treated in our institution from April 2010 to February 2016 were reviewed retrospectively. Twenty-seven patients who received 2–9 cycles of oxaliplatin-based NAC and 28 patients who received NACRT (45 Gy delivered in 25 fractions and 5-fluorouracil-based oral chemotherapy) were analyzed. The primary and secondary endpoints of the present study were the 3-year relapse-free survival (RFS) and the local and distant relapse rates, respectively.

Results

Regardless of the kind of neoadjuvant therapy, no patient experienced any grade 3–4 therapy-related adverse events. The frequent toxic events were grade 1 diarrhea in patients with NACRT and neutropenia in patients with NAC. A significantly higher proportion of patients with NAC underwent laparoscopic surgery and anterior resection (p = 0.037 and p = 0.003, respectively). The percentages of patients with lymph node yield less than 12 in the NAC group, and those in the NACRT group were 26 and 68%, respectively (p = 0.002). Comparing the NAC with the NACRT groups, the local relapse and distant relapse rates were 7.4 and 7.1% and 7.4 and 18%, respectively. There were no significant differences in 3-year RFS and 4-year overall survival (OS) between NAC and NACRT (3-year RFS 85.2 vs. 70.4%, p = 0.279; 4-year OS 96.3 vs. 89.1%, p = 0.145, respectively). With an analysis excluding patients who received postoperative adjuvant chemotherapy, no patients who received NAC had a distant relapse, and there was a significant difference in 3-year RFS compared with the NACRT groups (94.4 vs. 63.2%, p = 0.043).

Conclusion

These outcomes suggest that the therapeutic effect of oxaliplatin-based NAC is at least equal to that of NACRT and that NAC is a feasible and promising option for LARC.

https://ift.tt/2JzefLf

Longitudinal studies of the 18 F-FDG kinetics after ipilimumab treatment in metastatic melanoma patients based on dynamic FDG PET/CT

Abstract

Background

Immunotherapy has raised the issue of appropriate treatment response evaluation, due to the unique mechanism of action of the immunotherapeutic agents. Aim of this analysis is to evaluate the potential role of quantitative analysis of 2-deoxy-2-(¹⁸F)fluoro-d-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) data in monitoring of patients with metastatic melanoma undergoing ipilimumab therapy.

Methods

25 patients with unresectable metastatic melanoma underwent dynamic PET/CT (dPET/CT) of the thorax and upper abdomen as well as static, whole body PET/CT with ¹⁸F-FDG before the start of ipilimumab treatment (baseline PET/CT), after two cycles of treatment (interim PET/CT) and at the end of treatment after four cycles (late PET/CT). The evaluation of dPET/CT studies was based on semi-quantitative (standardized uptake value, SUV) calculation as well as quantitative analysis, based on two-tissue compartment modeling and a fractal approach. Patients' best clinical response, assessed at a mean of 59 weeks, was used as reference.

Results

According to their best clinical response, patients were dichotomized in those demonstrating clinical benefit (CB, n = 16 patients) and those demonstrating no clinical benefit (no-CB, n = 9 patients). No statistically significant differences were observed between CB and no-CB regarding either semi-quantitative or quantitative parameters in all scans. On contrary, the application of the recently introduced PET response evaluation criteria for immunotherapy (PERCIMT) led to a correct classification rate of 84% (21/25 patients).

Conclusion

Quantitative analysis of ¹⁸F-FDG PET data does not provide additional information in treatment response evaluation of metastatic melanoma patients receiving ipilimumab. PERCIMT criteria correlated better with clinical response.

https://ift.tt/2Lqcv4b

Combined effects of resveratrol and radiation in GH3 and TtT/GF pituitary adenoma cells

Abstract

Objective

Resveratrol and radiation decrease viability in various tumor cells. This study aims to investigate combined effects of resveratrol and radiation on viability, induction of apoptosis and necrosis, and expression of apoptosis modulators in rodent GH3 and TtT/GF pituitary adenoma cells in vitro.

Methods

Cells were incubated with 10–100 µM resveratrol. Medium and medium with ethanol served as controls. After 2 h, cells were irradiated with 0–5 Gray (Gy) and further incubated for 48–72 h. Cell viability was quantified using a hemocytometer. Cell death was assessed with an enzyme-linked immunosorbent assay (ELISA) that detects free nucleosomes in cell lysates and free nucleosomes released to the culture medium. Expression of B-cell lymphoma-2 protein (BCL-2) and BCL-2 associated Xprotein (BAX) was measured using quantitative real time-polymerase chain reaction (qRT-PCR) to analyze changes in BAX/BCL-2 ratio.

Results

Resveratrol and irradiation with 4 Gy alone and in combination significantly decreased cell viability (p = 0.017 and less). In the ELISA, 10 μM resveratrol significantly induced apoptosis in TtT/GF cells at 0 Gy (p < 0.001), but not at 3 or 5 Gy. In the ELISA, 10 μM resveratrol significantly induced necrosis in GH3 cells at 0, 3 and 5 Gy (p < 0.001). While qRT-PCR did not demonstrate a significant effect of 10 µM resveratrol or radiation on expression of BAX or BCL-2, a significant increase in the BAX/BCL-2 ratio was found after irradiation with 5 Gy in GH3 cells (p = 0.0027).

Conclusion

While moderate irradiation solely led to inhibited proliferation, resveratrol induced cell death in rodent pituitary adenoma cells.

https://ift.tt/2HpTXPa

P16 as a Prognostic Biomarker for Nonoropharyngeal Squamous Cell Cancers: Avatar or Mirage?

The etiologic implication and prognostic roles of p16-positive tumor status are well established for squamous cell cancers (SCCs) of the oropharynx (1) but remain controversial for nonoropharyngeal SCCs (non-OPCs) of the head and neck. In the oropharynx, human papillomavirus (HPV)–driven carcinogenesis leads to p16 overexpression, which renders p16 a logical surrogate for HPV tumor detection (2–4). However, non-OPCs do not have an analogous molecular profile. The overall prevalence of HPV- or p16-positive non-OPCs appears to be low (5–7). Furthermore, the proportion of p16-positive non-OPCs exceeds that for HPV-positive individuals (8–11), with only the former showing a survival benefit in limited studies (12). Therefore, consensus guidelines do not support testing of non-OPCs for HPV or p16 as their prognostic implications have not yet been established (13). In this issue of the Journal, Bryant et al. challenge this dogma by suggesting that p16 may still have prognostic value (14).

https://ift.tt/2sFvIqI

Adjuvant Anti-HER2 Therapy, Treatment-Related Amenorrhea, and Survival in Premenopausal HER2-Positive Early Breast Cancer Patients

Abstract

Background

In premenopausal patients with human epidermal growth factor receptor 2 (HER2)–positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown.

Methods

In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor–positive and –negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided.

Results

A total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor–positive disease. Median age was 43 (interquartile range = 38–47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab→lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P = .64). The association between TRA and survival outcomes differed according to hormone-receptor status (P_interaction for DFS = .007; P_interaction for OS = .003). For hormone receptor–positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor–negative patients.

Conclusions

In this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor–positive/HER2-positive early breast cancer patients.

https://ift.tt/2sECOg7

Prognostic Role of p16 in Nonoropharyngeal Head and Neck Cancer

Abstract

Background

Previous studies have reported conflicting information regarding the prognostic role of p16 in nonoropharyngeal head and neck squamous cell carcinoma (HNSCC).

Methods

Using the US Veterans Affairs database, we analyzed 1448 patients with locoregionally advanced HNSCC and known p16 status diagnosed between 2005 and 2015 and treated with surgery, radiotherapy, or chemoradiotherapy. Tumor p16 status was determined through manual review of pathology reports of primary tumor specimens. Oropharyngeal (n = 1061) or nonoropharyngeal (n = 387; hypopharyngeal, laryngeal, or oral cavity) tumor site was determined from tumor registry data and manually reviewed for accuracy. We used multivariable Cox regression to analyze the effect of p16 status on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) for oropharyngeal or nonoropharyngeal tumor sites. All statistical tests were two-sided.

Results

In multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16-positive tumors had improved OS, CSS, and CM compared with patients with p16-negative tumors in both oropharyngeal (OS: hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.40 to 0.71, P < .001; CSS: HR = 0.50, 95% CI = 0.35 to 0.73, P < .001; CM: HR = 0.59, 95% CI = 0.38 to 0.93, P = .02) and nonoropharyngeal primary sites (OS: HR = 0.41, 95% CI = 0.25 to 0.69, P < .001; CSS: HR = 0.37, 95% CI = 0.18 to 0.77, P = .008; CM: HR = 0.46, 95% CI = 0.23 to 0.95, P = .04). The prognostic impact of p16 status did not statistically significantly differ by primary tumor site for OS, CSS, or CM (P_interaction > .05).

Conclusions

Our findings support the hypothesis that p16 has a similar prognostic role in both nonoropharyngeal and oropharyngeal cancer. Consideration should be given to increased testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.

https://ift.tt/2HmeCmZ

What Can We Learn From Menstrual Patterns After Treatment for HER2-Positive Breast Cancer?

Treatment-related amenorrhea is a well-recognized consequence of chemotherapy in some premenopausal women (1). Amenorrhea is an imperfect surrogate for infertility and menopausal symptoms because it usually reflects at least temporary ovarian dysfunction. It has been associated with improved prognosis in hormone receptor–positive breast cancer (2–5). In a pivotal study published in the New England Journal of Medicine in 2010, Swain and colleagues reported that women with lymph node–positive breast cancer who experienced chemotherapy-related amenorrhea for six months or more had better disease-free survival and overall survival than those who did not across a variety of chemotherapy regimens, including doxorubicin and cyclophosphamide (AC) followed by docetaxel; concurrent AC and docetaxel; or concurrent doxorubicin and docetaxel (AT) (5). A subset analysis showed that this was true only in those with estrogen receptor (ER)–positive disease, who had a hazard ratio for death of 0.52 (P = .002) if they had experienced chemotherapy-related amenorrhea (6).

https://ift.tt/2kTU9xj

Validation of the Vectra XT three-dimensional imaging system for measuring breast volume and symmetry following oncological reconstruction

Abstract

Purpose

Three-dimensional surface imaging (3D-SI) of the breasts enables the measurement of breast volume and shape symmetry. If these measurements were sufficiently accurate and repeatable, they could be used in planning oncological breast surgery and as an objective measure of aesthetic outcome. The aim of this study was to validate the measurements of breast volume and symmetry provided by the Vectra XT imaging system.

Methods

To validate measurements, breast phantom models of true volume between 100 and 1000 cm³ were constructed and varying amounts removed to mimic breast tissue 'resections'. The volumes of the phantoms were measured using 3D-SI by two observers and compared to a gold standard. For intra-observer repeatability and inter-observer reproducibility in vivo, 16 patients who had undergone oncological breast surgery had breast volume and symmetry measured three times by two observers.

Results

A mean relative difference of 2.17 and 2.28% for observer 1 and 2 respectively was seen in the phantom measurements compared to the gold standard (n = 45, Bland Altman agreement). Intra-observer variation over ten repeated measurements demonstrated mean coefficients of variation (CV) of 0.58 and 0.49%, respectively. The inter-observer variation demonstrated a mean relative difference of 0.11% between the two observers. In patients, intra-observer variation over three repeated volume measurements for each observer was 3.9 and 3.8% (mean CV); the mean relative difference between observers was 5.78%. For three repeated shape symmetry measurements using RMS projection difference between the two breasts, the intra-observer variations were 8 and 14% (mean CV), the mean relative difference between observers was 0.43 mm for average symmetry values that ranged from about 3.5 to 15.5 mm.

Conclusion

This first validation of breast volume and shape symmetry measurements using the Vectra XT 3D-SI system suggests that these measurements have the potential to assist in pre-operative planning and also as a measure of aesthetic outcome.

https://ift.tt/2JaPIg1

Trastuzumab-induced cardiotoxicity and its risk factors in real-world setting of breast cancer patients

Abstract

Purpose

Cardiotoxicity is the most important side effect of trastuzumab treatment. Heart function monitoring is recommended during the treatment which has led to growing use of resources. The aim of this retrospective study was to determine the frequency and timing of trastuzumab cardiotoxicity and its risk factors in real-world setting.

Methods

Single institute, retrospective collection of data on HER2+ breast cancer patients (n = 246) was carried out through a pharmacy search for patients who had received trastuzumab in 2006–2014. Clinical and pathological factors, treatment history, EF measurements, cardiac medications, cardiovascular disease history, cardiac symptoms, and survival data were collected from patient records.

Results

32 patients (13%) had EF decline ≥ 10%, eleven (4.5%) had EF decline ≥ 20% within 1 year after trastuzumab initiation, and trastuzumab was discontinued due to suspected cardiotoxicity in six patients (2.4%). 49 patients (19.9%) experienced symptoms related to cardiotoxicity during therapy, which accumulated among those with EF drop. Underlying cardiovascular diseases and multiple (≥ 2) cardiac medications were related to EF drop (≥ 20%) and trastuzumab discontinuation. Majority of EF drops (≥ 10%) and trastuzumab discontinuations were seen within 6months of trastuzumab initiation and recovery of EF drop to < 10% of the baseline was seen in most cases (62.5%). There was no statistically significant difference in the survival of patients according to EF drop.

Conclusions

Trastuzumab cardiotoxicity seems to accumulate among patients with underlying cardiac conditions. EF monitoring could be targeted to risk groups without compromising of the cardiac health or survival of HER2-positive breast cancer patients.

https://ift.tt/2LZb0Lr

Adenocarcinoma of the oesophagus: neoadjuvant chemoradiation and radical surgery

Abstract

Purpose

To retrospectively evaluate long-term treatment results following neoadjuvant chemoradiation (CRT) and radical surgery in patients with advanced adenocarcinoma (AC) of the oesophagus.

Patients and methods

Between 2005 and 2015, a total of 102 consecutive patients with a median age of 64 years (range, 44–86 years) and AC of the oesophagus were evaluated of whom 84 received a full CRT. A group of 51 patients was treated with neoadjuvant intent followed by radical surgery. A total dose of 50.4 Gy with mostly weekly paclitaxel/fluorouracil chemotherapy was administered. Six to eight weeks following CRT, a transthoracic subtotal oesophageal and proximal gastric resection was performed. Survival curves for overall survival and no evidence of disease (NED) survival (primary endpoints) were calculated according to Kaplan–Meier, and possible prognostic factors were evaluated by the log-rank test as well as by a Cox regression analysis.

Results

Median follow-up time of the surviving patients was 48 months (range, 14–134 months). Overall and NED survival rates for patients of the study group (n = 51) were 40 and 32%, respectively, at 5 years. Age (p = 0.04), ypT category (p = 0.1) and the development of distant metastases (p = 0.05) were identified as (marginally) independent prognostic variables with impact on survival. Median survival time for patients of the study group (n = 51) was 45 ± 18 months (95%CI 9–81 months). Clear resection margins were achieved in 46/51 patients (92%). Regression rates with complete regression rare residual cancer and increased number of residual cells, but predominantly fibrosis were 33, 41, and 10%, respectively. Patterns of failure revealed local with distant recurrence in 2/51 (4%), regional recurrence alone in 2/51 (4%), and distant metastases in 27/51 (53%) patients.

Conclusion

Neoadjuvant CRT in patients with AC of the oesophagus followed by thoracoabdominal surgery is a locally very effective concept. A significant tumour regression in almost 75% of the patients may stimulate prospective trials on the omission of radical surgery for some elderly patients. Due to a high rate of distant metastases further investigations in terms of effective systemic therapy may be warranted.

https://ift.tt/2Js2u93

Myeloid neoplasms with t(16;21)(q24;q22)/ RUNX1-RUNX1T3 mimics acute myeloid leukemia with RUNX1-RUNX1T1

Abstract

Chromosome translocation t(16;21)(q24;q22)/RUNX1-RUNX1T3 is an infrequent but recurrent chromosomal abnormality identified in myeloid neoplasms, with only 25 cases have been reported to date. Here, we report eight cases (six women and two men) of myeloid neoplasms associated with t(16;21)(q24;q22): five with therapy-related myeloid neoplasms, two with relapsed acute myeloid leukemia (AML), and one with blast phase of chronic myeloid leukemia. Morphologic and immunophenotypic features include granulocytic dysplasia, blasts with prominent perinuclear hof, large orange-pink granules, long and slim Auer rods, and aberrant expression of CD19. Six patients received AML-based regimens, and five achieved complete remission after initial induction therapy. Our study suggests that myeloid neoplasm with t(16;21)/RUNX1-RUNX1T1 resembles AML with t(8;21)(q22;q22)/RUNX1-RUNX1T1, in regard to morphology, immunophenotype, and response to therapy. Therefore, the clinical management of AML with t(8;21) may provide the best model for patients with myeloid neoplasms with t(16;21).

https://ift.tt/2Jci6OD

Clinical characteristics and treatment outcome of an 86-year-old patient with acute myeloid leukaemia with acute promyelocytic-like morphology and uncommon RARA fusion variant

https://ift.tt/2HmfWX9

Cancers, Vol. 10, Pages 185: Cutting to the Chase: How Matrix Metalloproteinase-2 Activity Controls Breast-Cancer-to-Bone Metastasis

Cancers, Vol. 10, Pages 185: Cutting to the Chase: How Matrix Metalloproteinase-2 Activity Controls Breast-Cancer-to-Bone Metastasis

Cancers doi: 10.3390/cancers10060185

Authors: Marilena Tauro Conor C. Lynch

Bone metastatic breast cancer is currently incurable and will be evident in more than 70% of patients that succumb to the disease. Understanding the factors that contribute to the progression and metastasis of breast cancer can reveal therapeutic opportunities. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes whose role in cancer has been widely documented. They are capable of contributing to every step of the metastatic cascade, but enthusiasm for the use of MMP inhibition as a therapeutic approach has been dampened by the disappointing results of clinical trials conducted more than 20 years ago. Since the trials, our knowledge of MMP biology has expanded greatly. Combined with advances in the selective targeting of individual MMPs and the specific delivery of therapeutics to the tumor microenvironment, we may be on the verge of finally realizing the promise of MMP inhibition as a treatment strategy. Here, as a case in point, we focus specifically on MMP-2 as an example to show how it can contribute to each stage of breast-cancer-to-bone metastasis and also discuss novel approaches for the selective targeting of MMP-2 in the setting of the bone-cancer microenvironment.

https://ift.tt/2JaBPy9

Using Smaller than Standard Radiation Treatment Margins Does Not Change Survival Outcomes in High-grade Gliomas

Publication date: Available online 5 June 2018
Source:Practical Radiation Oncology
Author(s): Kripa Guram, Mark Smith, Timothy Ginader, Kellie Bodeker, Darrin Pelland, Edward Pennington, John M. Buatti
PurposeStudies evaluating treatment margins for high grade gliomas (HGG) are limited. We hypothesize patients with HGG treated with GTV to PTV expansion of 1cm or less will have similar progression-free survival (PFS) and overall survival (OS) as those treated according to standard RTOG or EORTC protocols. Furthermore, PFS and OS of subgroups within the study population, with GTV1 to PTV1 margins of 1.0cm and 0.4cm, will have equivalent survival outcomes.MethodsTreatment plans and outcomes for patients with pathologically confirmed HGG were analyzed (n=267). Survival (PFS and OS) was calculated from first radiation treatment. Chi-square test or Fisher's exact test was used to calculate associations between margin size and patient characteristics. Survival was estimated using Kaplan–Meier and compared using the log-rank test. All analyses were performed on the univariate level.ResultsMedian PFS and OS was 10.6 and 19.1months, respectively. By disease, median PFS and OS were 8.6 and 16.1months for glioblastoma (GBM) and 26.7 and 52.5months for anaplastic glioma (AG). Median follow-up was 18.3months. Treatment margin had no effect on outcome, with the 1.0cm GTV1-PTV1 margin subgroup (n=212) showing a median PFS and OS of 10.7 and 19.1months and the 0.4cm margin subgroup (n=55) showing a median PFS and OS of 10.2 and 19.3months. In comparison with the standard treatment with 2–3cm margins, there was not a significant difference in outcomes.ConclusionsThere is no apparent difference in survival when utilizing smaller margins compared to larger margins defined by RTOG and EORTC guidelines. While there remains no class I evidence that outcomes after treatment with smaller margins are identical to those after treatment with larger margins, this large series with long-term follow-up suggests reducing margins is safe and further investigation is warranted.



https://ift.tt/2LoNgiy

Unusual cause of obstructive uropathy: bilateral steinstrasse

Description 

A 45-year-old man presented with decreased urinary output (<150 mL per 24 hours), anorexia, nausea and bilateral flank pain for 1 week. His serum creatinine potassium were 12.9 mg/dL and 6.0 mEq/L, respectively. He had no associated comorbidity. He had history of bilateral renal pelvic stones for which he underwent extracorporeal shock wave lithotripsy (ESWL) 2 months back, first for the right kidney (single session) then 2 weeks later for the left kidney (single session). His renal function was normal before undergoing ESWL (serum creatinine 0.9 mg/dL). No check X-ray had been done after ESWL. A plain X-ray was done that showed bilateral steinstrasse (figure 1) and on ultrasonography he had hydronephrosis in both kidneys. This caused acute renal failure due to obstructive uropathy. He was taken up for haemodialysis urgently. After two sessions of haemodialysis, he was taken up for stenting of bilateral ureters. After stenting, his renal function...

https://ift.tt/2syxH0H

Unusual case of hypocalcaemia

Description 

A 33-year-old woman presented with 1 week of dizziness and bilateral leg and hand cramps with associated numbness and tingling. She stated she was diagnosed with hypocalcaemia when she was approximately 8 years old, but could not elaborate further. She was a poor historian with learning disabilities and admittedly was non-compliant with treatment.

Physical examination revealed a round face, short stature (4'10'') and obesity (body mass index 39) with no neck scars. Her extremities were notable brachydactyly of her feet (figure 1) as well as brachydactyly of her fourth and fifth fingers (figure 2) with a positive Archibald's sign (figure 3). X-ray of her hands was significant for shortening of the fourth and fifth metacarpals (figure 4). EKG was remarkable for prolonged QT interval (figure 5). Brain CT revealed extensive calcification in the basal ganglia (figure...

https://ift.tt/2sDp83O

Severe bone marrow suppression due to methotrexate toxicity following aceclofenac-induced acute kidney injury

Methotrexate is one of the most commonly used drugs in autoimmune disorders like rheumatoid arthritis. Gastrointestinal symptoms like nausea and stomatitis, skin rashes, alopecia, central nervous system symptoms like headache and confusion, hepatotoxicity and myelosuppression are some of the adverse effects. However, low oral doses on a weekly basis seldom show any signs of toxicity. Leucovorin or folinic acid is given along with methotrexate as rescue to reduce the toxic effects like bone marrow suppression. Non-steroidal anti-inflammatory drugs, like aceclofenac, are also used in chronic inflammatory conditions like rheumatoid arthritis and osteoarthritis. Nephrotoxicity is one of the adverse effects of both methotrexate and non-steroidal anti-inflammatory drugs; and its combined administration should be done with caution. This is a case of an elderly woman, a known case of rheumatoid arthritis, who presented in severe bone marrow suppression due to methotrexate toxicity following aceclofenac-induced acute kidney injury.

https://ift.tt/2syqk9s

ALL relapse with multiple cranial nerve palsies and toxic leukoencephalopathy: treatment failure with treatment toxicity

Description 

Acute lymphoblastic leukaemia (ALL) is one of the most common malignancies of childhood. ALL is treated with high doses of methotrexate (MTX) to prevent central nervous system (CNS) and haematological relapses. MTX is administered intravenously and via intrathecal route.1 MTX can cause neurotoxicity by disrupting CNS folate homeostasis or by direct neuronal damage. MTX-induced acute toxic leukoencephalopathy can result in acute neurological deficit, seizures or encephalopathy.2 We report a 27-year-old diagnosed case of ALL who presented with neurological symptoms 2 years after she was started with intensive and maintenance phase of chemotherapy. She took multiple cycles (24) of intrathecal MTX in her intensive phase and was subsequently followed up regularly after her maintenance phase for bone marrow aspiration, which showed reduced blast cells compared with the earlier report. Few weeks after completing her chemotherapy, she complained of visual blurring in the right eye followed by...

https://ift.tt/2sHj0HR

Differential diagnosis for chronic hypokalaemia

Doctors will often see patients with chronic hypokalaemia, frequently this is secondary to gastrointestinal losses, diuretics or renal disease. However, in this case report we review a rarer cause of chronic hypokalaemia—Gitelman syndrome (GS).

GS is an uncommon genetic disorder which causes primary renal tubular hypokalaemic metabolic alkalosis with secondary hypomagnesaemia and hypocalciuria. Although rare, it is important to remember GS when considering differential diagnoses for chronic hypokalaemia. We report the case of a woman who presented to the ophthalmology department with sclerochoroidal calcification. An ophthalmologist was reviewing the medical literature, which prompted them to investigate for GS. A diagnosis was formed at that time based on the blood and urine chemistry results. However, later we were able to offer the patient genetic testing, which confirmed our provisional diagnosis.

https://ift.tt/2kOgc8n

Gitelman syndrome and primary hyperparathyroidism: a rare association

Gitelman syndrome(GS) is a rare autosomal recessive salt-losing tubulopathy of young adults, characterised by hypokalaemia, hypomagnesaemia, hypocalciuria and secondary hyperaldosteronism. Hypercalcaemia due to hypocalciuria in these patients is extremely rare.

A 25-year-old healthy woman was referred to the Endocrinology clinic for evaluation of persistent hypokalaemia. She presented with fatigue, myalgias, cramps and paraesthesia. Her physical examination was normal. Laboratory workup revealed: K⁺ 2.7 mEq/L (r.v.3.5–5.1), 24 hours urinary K⁺ 84.7 mEq/24 hours (r.v.25–125), Mg²⁺ 0.71 mg/dL (r.v.1.6–2.6), 24 hours urinary Mg²⁺ 143.1 mg/24 hours (r.v.73–122), Ca²⁺ 12 mg/dL (r.v.8.4–10.2), aldosterone 47.1 ng/mL (r.v. 4–31) and active renin 374.7 uUI/mL (r.v.4.4–46.1). She was diagnosed with GS and was treated with spironolactone, oral K⁺ and Mg²⁺ supplementation. Further investigation confirmed hypercalcaemia due to primary hyperparathyroidism owing to a single parathyroid adenoma. Following parathyroidectomy serum calcium normalised.

Current knowledge favours that hypomagnesaemia in patients with GS protects them from hypercalcaemia. In this context of multiple electrolyte imbalances, correction of hypomagnesaemia is a challenge and should be done carefully. Like in our patient, aetiology of hypercalcaemia should be promptly diagnosed and reversed.

https://ift.tt/2Hjwfny

Serious life-threatening multifocal infection in a child, caused by Panton-Valentine leucocidin-producing Staphylococcus aureus (PVL-MSSA)

Groin pain is a frequently occurring complaint in presentations to the Emergency Department. Muscular sprain is often a differential diagnosis, however serious conditions such as pyomyositis should not be ignored. This case report presents a child with atraumatic right groin pain, which was initially diagnosed as a muscular sprain. The patient later re-presented out of hours to the Emergency Department with what was found to be extensive pelvic abscesses. He was subsequently found to have bilateral pneumonia and later developed a pericardial effusion and osteomyelitis of the right iliac bone, sacroiliac joint and sacrum. With multiple surgical interventions and appropriate antibiotics, he made a full recovery and was discharged home after a total admission time of 41 days. The causative organism was found to be Panton-Valentine leucocidin-positive methicillin-susceptible Staphylococcus aureus.

https://ift.tt/2syqayS

Aspiration and altered airway anatomy: a presentation with a twist

Description 

A 60-year-old woman presented to our hospital with severe hypercapnic respiratory failure in the absence of a prior smoking history. She reported a 1-day history of increased dyspnoea and a cough productive of green sputum. Her medical history was significant for severe idiopathic scoliosis, cleft palate repair, rheumatoid arthritis, hypothyroidism and recurrent lower respiratory tract infections. She was obtunded on presentation and required 24 hours of mechanical ventilation.

A CT thorax was performed to further investigate her acute deterioration. Considerable distortion of thoracic anatomy secondary to kyphoscoliosis was noted. Right lower lobe atelectasis due to extrinsic compression of the bronchus intermedius by thoracic vertebrae and left lower lobe consolidation were reported (figures 1–3). Due to the vertical orientation of the left main bronchus (LMB), aspiration pneumonia was suspected (figure 2). Our patient initially improved with antimicrobial therapy, dietary modifications and...

https://ift.tt/2sDp7Ni

Rapidly involuting congenital haemangioma of the liver

Rapidly involuting congenital haemangiomas (RICHs) are rare benign vascular tumours of infancy. They are generally asymptomatic, but can present with thrombocytopaenia and coagulopathy. Significant complications including life-threatening bleeding, high-output heart failure and liver failure, though rare, can occur. RICHs generally regress by 12–14 months of age and can be managed clinically with symptomatic treatment, watchful waiting and close monitoring of the size of the haemangioma. Medical management (corticosteroids, propranolol) has not shown to be effective, in contrast to infantile haemangioma which will not regress spontaneously and has been noted to respond to medical therapy. Awareness of this diagnosis is important to prevent unnecessary medical and surgical intervention. Here, we present a case of a full-term infant with RICH who presented with thrombocytopaenia and abnormal coagulation profile. The coagulopathy was treated symptomatically, while the lesion was observed with serial ultrasounds and gradually decreased in size.

https://ift.tt/2swJP2g

Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Abstract

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are used in the management of selected peritoneal malignancies. While most patients achieve long-term disease-free survival, there remains a group with early recurrence (ER). We aim to investigate the clinical factors associated with ER.

Methods

A retrospective review of a prospectively maintained database of CRS-HIPEC patients treated between April 2001 and Feb 2016 was performed. ER was defined as recurrence within 12 months of CRS-HIPEC. Patients were stratified according to time to recurrence and only patients with at least 12-month follow-up were included. Perioperative factors were investigated, and subgroup analyses of colorectal, ovarian and appendiceal groups were performed.

Results

Of the 144 patients included, 30.6% were colorectal, 36.8% ovarian and primary peritoneal, 24.3% appendiceal, 2.1% mesothelioma and 6.3% were of other origins. Thirty-nine patients (27%) suffered ER. Univariable and multivariable analyses revealed that primary tumour type (p = 0.02) and post-CRS adjuvant treatment (p = 0.04) were associated with ER. Appendiceal patients had a lower odds of ER compared to colorectal patients [OR = 0.15 (0.043–0.502) p < 0.002]. Patients who received post-CRS adjuvant treatment had a lower odds of ER than patients without adjuvant treatment [OR = 0.32; (0.128–0.818) p = 0.02].

Conclusion

There remains a 27% risk of ER after CRS-HIPEC. Better patient selection and the administration of adjuvant chemotherapy may help to reduce ER.

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Secondary cancer after a childhood cancer diagnosis: viewpoints considering primary cancer

Abstract

Backgrounds

Multidisciplinary therapy has increased the risk of subsequent late effects, but detailed analyses on secondary cancers in childhood cancer survivors (CCSs) are limited in Asian countries.

Methods

This was a retrospective cohort study comprising 10,069 CCSs who were diagnosed between 1980 and 2009 across 15 Japanese hospitals. We conducted secondary analyses to estimate the incidence of secondary cancer according to each primary malignancy and to elucidate the association between primary and secondary cancers. We also explored the risk factors for the development of secondary cancer in each independent primary malignancy.

Results

The cumulative incidence of secondary cancer at 20 years varied among primary cancers: hematological malignancy, 3.1% (95% CI 2.2–4.3); retinoblastoma, 6.6% (95% CI 1.5–16.8); pediatric solid tumor, 2.5% (95% CI 1.3–4.2); brain tumors, 5.2% (95% CI 1.7–11.8) bone/soft tissue sarcoma, 5.2% (95% CI 2.3–10.1); and others, 3.3% (95% CI 1.6–6.0) (p = 0.015). The cumulative incidence of secondary cancers is highest in those with osteosarcoma (13.1%) followed by those with hepatoblastoma (8.4%) and retinoblastoma (6.6%). Close association between the primary and secondary cancer diagnoses was found. The risk factors for secondary cancer development depended on the primary cancer, but autologous/allogeneic stem cell transplantation was a relatively common risk factor.

Conclusion

The cumulative incidence of secondary cancer varied among primary cancers. The primary cancer was closely associated with the secondary cancer but stem cell transplantation was a common risk factor for secondary cancers among CCSs.

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Aldoxorubicin therapy for the treatment of patients with advanced soft tissue sarcoma

Future Oncology, Ahead of Print.


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A head-to-head Phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia

Future Oncology, Ahead of Print.


https://ift.tt/2JhBYvO

Patterns of increased incidence and survival of cutaneous melanoma in Girona (Spain) 1994–2013: a population-based study

Abstract

Introduction

We conducted a population-based study on the Girona Cancer Registry (Spain) for the period 1994–2013 to determine patterns of change in the incidence of melanoma, which is increasing in many countries, and patient survival in our geographical area.

Materials and methods

Using the standard registration rules for cancer registries, we calculated crude and standardized incidence rates as well as their trends. We also analysed the observed survival, 1-year conditioned survival and relative survival at 3, 5 and 10 years.

Results

Our crude incidence rate was 9.13 cases/100,000 inhabitants for invasive and 2.59 for "in situ" melanomas. A statistically significant increase in incidence was found for melanomas of less than 1 mm in Breslow index and in males. 10-year observed and relative survival rates were 64.1 and 83.1%, respectively.

Conclusions

We found an increasing trend in the incidence of low-risk melanoma and a survival rate similar to that reported elsewhere in Europe.

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Title: Choosing Wisely at the end of life: use of shorter courses of palliative radiation for bone metastasis

Publication date: Available online 4 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Audrey S. Wallace, John B. Fiveash, Courtney P. Williams, Elizabeth Kvale, Maria Pisu, Bradford E. Jackson, Gabrielle B. Rocque
PurposeAmerican Society of Radiation Choosing Wisely guidelines recommend <10 fractions of radiation (RT) for bone metastasis, with consideration for 1 fraction in poor prognosis patients. The purpose of this analysis is to evaluate characteristic differences in guideline concordance to fractionation regimens in a modern cohort of older patients with diagnosis of bone metastasis.Methods and MaterialsMedicare beneficiaries 65 year of age or older treated with radiation for bone metastasis from 2012-2015 were identified. Guideline concordant radiation fractionation was defined in the entire cohort as 10 or fewer fractions. Utilization of 1 vs. 2 or more fractions was analyzed in deceased patients. Patient demographic, disease, and facility characteristics associated with shorter fractionation were analyzed.ResultsIn 569 patients treated with RT, median age at diagnosis was 73 years. The most common cancer types were lung (37%), genitourinary (26%), breast (15%), and gastrointestinal (10%). In all patients, 34%, 30%, and 36% received 1, 2-10, and 11+ fractions respectively. In comparison to 1-10 fractions, 11+ fractions were associated with $1467 increase cost to Medicare during the calendar quarter of RT per patient. Almost 2/3 of patients who died within 30 days of RT completion were treated with more than 1 fraction.ConclusionWhile guideline concordance was high overall, a large number of patients received longer courses of RT at the end of life. Strong consideration should be made for utilization of shorter courses particularly in patients with limited prognosis.

Teaser

This population based analysis shows increasing utilization of ASTRO guideline concordant fractionation for palliation of bone metastasis at 64% However, nearly 2/3 of patients received more than 1 fraction of RT in the last 30 days of life.


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Cancers, Vol. 10, Pages 183: Clinico-Pathological Importance of TGF-β/Phospho-Smad Signaling during Human Hepatic Fibrocarcinogenesis

Cancers, Vol. 10, Pages 183: Clinico-Pathological Importance of TGF-β/Phospho-Smad Signaling during Human Hepatic Fibrocarcinogenesis

Cancers doi: 10.3390/cancers10060183

Authors: Katsunori Yoshida Koichi Matsuzaki Miki Murata Takashi Yamaguchi Kanehiko Suwa Kazuichi Okazaki

Chronic viral hepatitis is a global public health problem, with approximately 570 million persons chronically infected. Hepatitis B and C viruses increase the risk of morbidity and mortality from liver cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic complications that develop. Hepatitis virus infection induces transforming growth factor (TGF)-&beta;, which influences microenvironments within the infected liver. TGF-&beta; promotes liver fibrosis by up-regulating extracellular matrix production by hepatic stellate cells. TGF-&beta; is also up-regulated in patients with HCC, in whom it contributes importantly to bringing about a favorable microenvironment for tumor growth. Thus, TGF-&beta; is thought to be a major factor regulating liver fibrosis and carcinogenesis. Since TGF-&beta; carries out regulatory signaling by influencing the phosphorylation of Smads, we have generated several kinds of phospho-specific antibodies to Smad2/3. Using these, we have identified three types of phospohorylated forms: COOH-terminally phosphorylated Smad2/3 (pSmad2C and pSmad3C), linker phosphorylated Smad2/3 (pSmad2L and pSmad3L), and dually phosphorylated Smad3 (pSmad2L/C and pSmad3L/C). TGF-&beta;-mediated pSmad2/3C signaling terminates cell proliferation; on the other hand, cytokine-induced pSmad3L signaling accelerates cell proliferation and promotes fibrogenesis. This review addresses TGF-&beta;/Smad signal transduction in chronic liver injuries and carcinogenic processes. We also discuss the reversibility of Smad signaling after antiviral therapy.

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Cancers, Vol. 10, Pages 184: RIPK2: New Elements in Modulating Inflammatory Breast Cancer Pathogenesis

Cancers, Vol. 10, Pages 184: RIPK2: New Elements in Modulating Inflammatory Breast Cancer Pathogenesis

Cancers doi: 10.3390/cancers10060184

Authors: Alaa Zare Alexandra Petrova Mehdi Agoumi Heather Amstrong Gilbert Bigras Katia Tonkin Eytan Wine Shairaz Baksh

Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that is associated with significantly high mortality. In spite of advances in IBC diagnoses, the prognosis is still poor compared to non-IBC. Due to the aggressive nature of the disease, we hypothesize that elevated levels of inflammatory mediators may drive tumorigenesis and metastasis in IBC patients. Utilizing IBC cell models and patient tumor samples, we can detect elevated NF-&kappa;B activity and hyperactivation of non-canonical drivers of NF-&kappa;B (nuclear factor kappaB)-directed inflammation such as tyrosine phosphorylated receptor-interacting protein kinase 2 (pY RIPK2), when compared to non-IBC cells or patients. Interestingly, elevated RIPK2 activity levels were present in a majority of pre-chemotherapy samples from IBC patients at the time of diagnosis to suggest that patients at diagnosis had molecular activation of NF-&kappa;B via RIPK2, a phenomenon we define as &ldquo;molecular inflammation&rdquo;. Surprisingly, chemotherapy did cause a significant increase in RIPK2 activity and thus molecular inflammation suggesting that chemotherapy does not resolve the molecular activation of NF-&kappa;B via RIPK2. This would impact on the metastatic potential of IBC cells. Indeed, we can demonstrate that RIPK2 activity correlated with advanced tumor, metastasis, and group stage as well as body mass index (BMI) to indicate that RIPK2 might be a useful prognostic marker for IBC and advanced stage breast cancer.

https://ift.tt/2JrM3tn

MEF2 and the tumorigenic process, hic sunt leones

Publication date: Available online 5 June 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Eros Di Giorgio, Wayne W. Hancock, Claudio Brancolini
While MEF2 transcription factors are well known to cooperate in orchestrating cell fate and adaptive responses during development and adult life, additional studies over the last decade have identified a wide spectrum of genetic alterations of MEF2 in different cancers. The consequences of these alterations, including triggering and maintaining the tumorigenic process, are not entirely clear. A deeper knowledge of the molecular pathways that regulate MEF2 expression and function, as well as the nature and consequences of MEF2 mutations are necessary to fully understand the many roles of MEF2 in malignant cells. This review discusses the current knowledge of MEF2 transcription factors in cancer.



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Adjuvant and neoadjuvant approaches for urothelial cancer: updated indications and controversies

Publication date: Available online 5 June 2018
Source:Cancer Treatment Reviews
Author(s): Francesco Massari, Matteo Santoni, Vincenzo di Nunno, Liang Cheng, Antonio Lopez-Beltran, Alessia Cimadamore, Silvia Gasparrini, Marina Scarpelli, Nicola Battelli, Rodolfo Montironi
Urothelial carcinoma (UC) of the bladder and upper urinary tract still results an open challenge for clinical oncologists. Excluding selected patients who will particularly benefit from chemo-radiotherapy combined to endoscopic tumour removal, surgery represents the only curative approach for localized stages. Unfortunately, over 50% of operated patients do experience local or distant recurrence of the disease. Several pre and/or postoperative treatments are under evaluation in patients with UC in order to effectively reduce the difficulty and morbidity of more extensive procedures and to increase the Disease-Free Survival (DFS). The number of trials has been rapidly increased by the development of immunocheckpoint inhibitors, used alone or in combined strategies with chemotherapy, radiotherapy or other immunotherapies. The aim of this review is to illustrate the current status of neoadjuvant and adjuvant treatments in UC focusing our attention to the major ongoing trials in these settings.



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Maintenance Treatment of Recurrent Ovarian Cancer: Is It Ready for Prime Time?

Publication date: Available online 5 June 2018
Source:Cancer Treatment Reviews
Author(s): Paul DiSilvestro, Angeles Alvarez Secord
Approximately 1% of women in the United States will be diagnosed with epithelial ovarian cancer (EOC) during their lifetime. It is most likely to present at a more advanced stage, requiring aggressive therapeutic measures, and most women will succumb to this illness. Due to advancements in therapy, the oncology community has begun to shift its focus to molecular targeted agents, alternative dosing schedules, and maintenance therapy. Women who achieve a response to initial adjuvant chemotherapy may be candidates for maintenance therapy, with the goal of inducing a lasting remission or prolonging the disease-free interval before recurrence. The rationale for maintenance therapy is to delay disease progression by eliminating residual, slowly-dying cancerous cells, or impeding cell turnover. This review discusses the goals of maintenance therapy for EOC with antiangiogenic agents or poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and reviews clinical studies that have demonstrated improvements in survival outcomes. The side-effect profiles for PARP inhibitors and the implications for preserving quality of life during maintenance therapy will also be discussed.



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The relationship between patient and tumor characteristics, patterns of breast cancer care, and 5-year survival among elderly women with incident breast cancer

Abstract

Purpose

To examine the relationship between patient and tumor characteristics, patterns of breast cancer care, and 5-year survival among a population-based cohort of elderly women with incident breast cancer, with a special focus on identifying sources of socioeconomic (SES) disparities in outcomes.

Methods

We identified women with newly diagnosed breast cancer in 2006–2009 from the Surveillance and Epidemiology End Result study linked with Medicare claims. A Classification and Regression Tree (CART) model was applied to 13 individual indicators of neoadjuvant and adjuvant breast cancer treatment, tumor characteristics, and patient sociodemographic variables to identify patterns with the greatest discriminant value in predicting 5-year survival. We subsequently examined the extent to which these patterns varied by the patient's SES.

Results

Survival probabilities associated with the 18 unique CART-identified patterns ranged from 22 to 87%. The number of positive axillary nodes was the best single discriminator between high and lower survival outcomes. The most common discriminant factor among patterns with poor (< 25%) survival was the absence of radiation treatment, followed by the presence of comorbidities, tumor size > 2 cm, and no breast surgery. Relative to high SES women, poor women were nearly four times (12.3% vs. 3.2%, p < 0.001) as likely to be classified in the pattern associated with worse survival, and less likely (31.7% vs. 52.9%, p = 0.04) to receive the pattern associated with the greatest survival.

Conclusions

Greater adoption of effective patterns of care could improve survival of elderly women with incident breast cancer overall, and reduce SES disparities therein.

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Rethinking medulloblastoma from a targeted therapeutics perspective

Abstract

Introduction

Medulloblastoma is an aggressive but potentially curable central nervous system tumor that remains a treatment challenge. Analysis of therapeutic targets can provide opportunities for the selection of agents.

Methods

Using multiplatform analysis, 36 medulloblastomas were extensively profiled from 2009 to 2015. Immunohistochemistry, next generation sequencing, chromogenic in situ hybridization, and fluorescence in situ hybridization were used to identify overexpressed proteins, immune checkpoint expression, mutations, tumor mutational load, and gene amplifications.

Results

High expression of MRP1 (89%, 8/9 tumors), TUBB3 (86%, 18/21 tumors), PTEN (85%, 28/33 tumors), TOP2A (84%, 26/31 tumors), thymidylate synthase (TS; 80%, 24/30 tumors), RRM1 (71%, 15/21 tumors), and TOP1 (63%, 19/30 tumors) were found in medulloblastoma. TOP1 was found to be enriched in metastatic tumors (90%; 9/10) relative to posterior fossa cases (50%; 10/20) (p = 0.0485, Fisher exact test), and there was a positive correlation between TOP2A and TOP1 expression (p = 0.0472). PD-1 + T cell tumor infiltration was rare, PD-L1 tumor expression was uncommon, and TML was low, indicating that immune checkpoint inhibitors as a monotherapy should not necessarily be prioritized for therapeutic consideration based on biomarker expression. Gene amplifications such as those of Her2 or EGFR were not found. Several unique mutations were identified, but their rarity indicates large-scale screening efforts would be necessary to identify sufficient patients for clinical trial inclusion.

Conclusions

Therapeutics are available for several of the frequently expressed targets, providing a justification for their consideration in the setting of medulloblastoma.

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Including internal mammary lymph nodes in radiation therapy for synchronous bilateral breast cancer: an international survey of treatment technique and clinical priorities

Abstract

Purpose

The aim of this study was to understand the international standard practice for radiation therapy treatment techniques and clinical priorities for institutions including the internal mammary lymph nodes (IMLNs) in the target volume for patients with synchronous bilateral breast cancer.

Methods

An international survey was developed to include questions that would provide awareness of favored treatment techniques, treatment planning and delivery resource requirements, and the clinical priorities that may lead to the utilization of preferred treatment techniques.

Results

Of the 135 respondents, 82 indicated that IMLNs are regularly included in the target volume for radiation therapy (IMLN-inclusion) when the patient is otherwise generally indicated for regional nodal irradiation. Of the 82 respondents that regularly include IMLNs, five were removed as those respondents do not treat this population synchronously. Of the 77 respondents, institutional standard of care varied significantly, though VMAT (34%) and combined static photon and electron fields (21%) were the most commonly utilized techniques. Respondents did preferentially select target volume coverage (70%) as the most important clinical priority, followed by normal tissue sparing (25%).

Conclusion

The results of the survey indicate that the IMLN-inclusion for radiation therapy has not yet been comprehensively adopted. As well, no consensus on best practice for radiation therapy treatment techniques has been reached.

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N-Terminal Myristoylated VP5 is Required for Penetrating Cell Membrane and Promoting Infectivity in Aquareoviruses

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